Author: "Obel, N" / Topic: viral load - Searchworks@Jio Institute Digital Library Search Results

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1. Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

Author: McLaren PJ, Porreca I, Iaconis G, Mok HP, Mukhopadhyay S, Karakoc E, Cristinelli S, Pomilla C, Bartha I, Thorball CW, Tough RH, Angelino P, Kiar CS, Carstensen T, Fatumo S, Porter T, Jarvis I, Skarnes WC, Bassett A, DeGorter MK, Sathya Moorthy MP, Tuff JF, Kim EY, Walter M, Simons LM, Bashirova A, Buchbinder S, Carrington M, Cossarizza A, De Luca A, Goedert JJ, Goldstein DB, Haas DW, Herbeck JT, Johnson EO, Kaleebu P, Kilembe W, Kirk GD, Kootstra NA, Kral AH, Lambotte O, Luo M, Mallal S, Martinez-Picado J, Meyer L, Miro JM, Moodley P, Motala AA, Mullins JI, Nam K, Obel N, Pirie F, Plummer FA, Poli G, Price MA, Rauch A, Theodorou I, Trkola A, Walker BD, Winkler CA, Zagury JF, Montgomery SB, Ciuffi A, Hultquist JF, Wolinsky SM, Dougan G, Lever AML, Gurdasani D, Groom H, Sandhu MS, and Fellay J
Subjects: Humans, Cell Line, Africa, Chromosomes, Human, Pair 1 genetics, Alleles, RNA, Long Noncoding genetics, Virus Replication, DNA Helicases genetics, DNA Helicases metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Genetic Variation, HIV Infections genetics, HIV-1 growth & development, HIV-1 physiology, Viral Load genetics
Abstract: HIV-1 remains a global health crisis 1 , highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa 2 , we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV 3 . We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log 10 -transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair 4 . Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2023
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2. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.

Author: Thørner LW, Erikstrup C, Harritshøj LH, Larsen MH, Kronborg G, Pedersen C, Larsen CS, Pedersen G, Gerstoft J, Obel N, and Ullum H
Subjects: Adult, Alleles, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, DNA-Binding Proteins immunology, Denmark, Female, Gene Expression, Gene Frequency, Genotype, HIV Infections drug therapy, HIV Infections immunology, HIV Infections virology, HIV-1 drug effects, HIV-1 growth & development, HLA-C Antigens immunology, Humans, Male, Middle Aged, Prospective Studies, RNA, Long Noncoding, RNA, Untranslated immunology, Viral Load drug effects, Viral Load immunology, Anti-Retroviral Agents therapeutic use, DNA-Binding Proteins genetics, HIV Infections genetics, HLA-C Antigens genetics, Polymorphism, Single Nucleotide, RNA, Untranslated genetics, Viral Load genetics
Abstract: Aims: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART)., Material and Methods: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects., Results: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART., Conclusions: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART., (Copyright © 2016 Elsevier B.V. All rights reserved.)
Published: 2016
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3. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

Author: McLaren PJ, Coulonges C, Bartha I, Lenz TL, Deutsch AJ, Bashirova A, Buchbinder S, Carrington MN, Cossarizza A, Dalmau J, De Luca A, Goedert JJ, Gurdasani D, Haas DW, Herbeck JT, Johnson EO, Kirk GD, Lambotte O, Luo M, Mallal S, van Manen D, Martinez-Picado J, Meyer L, Miro JM, Mullins JI, Obel N, Poli G, Sandhu MS, Schuitemaker H, Shea PR, Theodorou I, Walker BD, Weintrob AC, Winkler CA, Wolinsky SM, Raychaudhuri S, Goldstein DB, Telenti A, de Bakker PI, Zagury JF, and Fellay J
Subjects: Adult, Alleles, Amino Acids genetics, Chromosomes, Human, Pair 3 genetics, Genome-Wide Association Study, HLA-B Antigens genetics, Humans, Inheritance Patterns genetics, Physical Chromosome Mapping, Receptors, CCR5 genetics, Genetic Predisposition to Disease, HIV-1 genetics, Host-Pathogen Interactions genetics, Polymorphism, Single Nucleotide genetics, Viral Load genetics
Abstract: Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.
Published: 2015
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4. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients.

Author: Vandenhende MA, Ingle S, May M, Chene G, Zangerle R, Van Sighem A, Gill MJ, Schwarze-Zander C, Hernandez-Novoa B, Obel N, Kirk O, Abgrall S, Guest J, Samji H, D'Arminio Monforte A, Llibre JM, Smith C, Cavassini M, Burkholder GA, Shepherd B, Crane HM, Sterne J, and Morlat P
Subjects: Adult, Antiretroviral Therapy, Highly Active methods, Europe, Female, HIV Infections mortality, HIV Infections pathology, Humans, Male, Middle Aged, North America, Prognosis, Survival Analysis, Treatment Outcome, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, HIV-1 isolation & purification, Viral Load, Viremia
Abstract: Background: The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown., Objective: Assess the association of different levels of LLV with virological failure, AIDS event, and death among HIV-infected patients receiving combination ART., Methods: We analyzed data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration. Eligible patients achieved viral load below 50 copies/ml within 3-9 months after ART initiation. LLV50-199 was defined as two consecutive viral loads between 50 and 199 copies/ml and LLV200-499 as two consecutive viral loads between 50 and 499 copies/ml, with at least one between 200 and 499 copies/ml. We used Cox models to estimate the association of LLV with virological failure (two consecutive viral loads at least 500 copies/ml or one viral load at least 500 copies/ml, followed by a modification of ART) and AIDS event/death., Results: Among 17 902 patients, 624 (3.5%) experienced LLV50-199 and 482 (2.7%) LLV200-499. Median follow-up was 2.3 and 3.1 years for virological and clinical outcomes, respectively. There were 1903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure [adjusted hazard ratio (aHR) 3.97, 95% confidence interval (CI) 3.05-5.17]. LLV50-199 was weakly associated with virological failure (aHR 1.38, 95% CI 0.96-2.00). LLV50-199 and LLV200-499 were not associated with AIDS event/death (aHR 1.13, 95% CI 0.81-1.68; and aHR 0.95, 95% CI 0.62-1.48, [corrected] respectively)., Conclusion: LLV200-499 was strongly associated with virological failure, but not with AIDS event/death. Our results support the US guidelines, which define virological failure as a confirmed viral load above 200 copies/ml.
Published: 2015
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5. No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010.

Author: Helleberg M, Kronborg G, Larsen CS, Pedersen G, Pedersen C, Obel N, and Gerstoft J
Subjects: Adult, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Cohort Studies, Denmark, Female, HIV Infections drug therapy, HIV Infections immunology, Humans, Male, Middle Aged, Time Factors, Virulence, HIV Infections pathology, HIV Infections virology, HIV-1 isolation & purification, HIV-1 pathogenicity, Viral Load
Abstract: Objectives: Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark., Methods: We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/μL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count < 350 cells/μL was compared among patients diagnosed in 1995-2000, 2001-2005 and 2006-2010., Results: We followed 1469 HIV-infected patients for a total of 5783 person-years. The median viral set point was 4.27 log10 HIV-1 RNA copies/mL [interquartile range (IQR) 3.58-4.73 log10 copies/mL]. The median CD4 cell decline per year was 57 cells/μL (IQR 10-139 cells/μL). In analyses adjusted for age, gender, origin, route of transmission and CD4 count at diagnosis, there were no associations between year of diagnosis and viral set point or CD4 cell decline. Time to first CD4 count < 350 cells/μL did not change in the study period [incidence rate ratio (IRR) 0.90 (95% confidence interval (CI) 0.76-1.06) for 2001-2005 and 1.09 (95% CI 0.79-1.34) for 2006-2010 compared with 1995-2000]., Conclusions: We found no evidence of changing trends in viral set point, CD4 cell decline or time to CD4 count < 350 cells/μL during the period 1995-2010 in a cohort of chronically HIV-infected individuals., (© 2013 British HIV Association.)
Published: 2013
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6. Poor CD4 response despite viral suppression is associated with increased non-AIDS-related mortality among HIV patients and their parents.

Author: Helleberg M, Kronborg G, Larsen CS, Pedersen G, Pedersen C, Obel N, and Gerstoft J
Subjects: Acquired Immunodeficiency Syndrome immunology, Acquired Immunodeficiency Syndrome virology, Adult, Denmark epidemiology, Female, Humans, Incidence, Male, Parents, Survival Analysis, Acquired Immunodeficiency Syndrome drug therapy, Acquired Immunodeficiency Syndrome mortality, Anti-HIV Agents administration & dosage, CD4-Positive T-Lymphocytes immunology, Viral Load
Abstract: Introduction: Poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS-related morbidity and on mortality in HIV patients and their parents., Methods: Mortality rates were estimated among 1758 virally suppressed patients in the Danish HIV Cohort Study after 2 years on HAART and among their parents (n = 1603). Analyses were stratified by pre-HAART CD4 count and CD4 increase. Incidence rate ratios (IRRs) of non-AIDS-related morbidity and mortality rate ratios (MRR) were analyzed using Poisson regression., Results: CD4 increases less than 25 vs. more than 100 cells/μl was associated with increased mortality [MRR 3.5 (95% confidence interval (CI) 1.8-6.8)] even in individuals with pre-HAART CD4 cell count more than 250 cells/μl (MRR 3.2 (95%CI, 1.3-7.8). Mortality of parents of patients with poor CD4 response was also increased [MRR 1.5 (95%CI, 1.1-2.1)]. There was a trend towards association between poor CD4 response and increased risk of cardiovascular disease and cancer [IRR 1.6 (95%CI, 0.8-3.2) and 1.6 (95%CI, 0.6-4.8)]., Conclusion: Poor CD4 increase post-HAART is associated with adverse prognosis even in absence of severe immunosuppression. CD4 response in HIV patients is associated with mortality among their parents, thus poor CD4 response may be caused by genetic factors, which might also affect morbidity and mortality in the HIV-negative population.
Published: 2013
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7. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

Author: Young J, Psichogiou M, Meyer L, Ayayi S, Grabar S, Raffi F, Reiss P, Gazzard B, Sharland M, Gutierrez F, Obel N, Kirk O, Miro JM, Furrer H, Castagna A, De Wit S, Muñoz J, Kjaer J, Grarup J, Chêne G, and Bucher H
Subjects: Adult, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections drug therapy, Humans, Longitudinal Studies, Male, Acquired Immunodeficiency Syndrome etiology, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, HIV Infections complications, HIV Infections mortality, Viral Load drug effects
Abstract: Background: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load., Methods and Findings: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl., Conclusions: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.
Published: 2012
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8. Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study.

Author: Engsig FN, Gerstoft J, Kronborg G, Larsen CS, Pedersen G, Røge B, Jensen J, Nielsen LN, and Obel N
Subjects: Adult, Age Factors, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections immunology, Humans, Immune Tolerance, Male, Middle Aged, Risk Factors, Survival Analysis, Time Factors, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active, Blood virology, HIV Infections drug therapy, HIV Infections mortality, Viral Load
Abstract: Background: The mortality in patients with persistent low CD4 count despite several years of HAART with sustained viral suppression is poorly documented. We aimed to identify predictors for inadequate CD4 cell recovery and estimate mortality in patients with low CD4 count but otherwise successful HAART., Method: In a nationwide cohort of HIV patients we identified all individuals who started HAART before 1 January 2005 with CD4 cell count ≤ 200 cells/μL and experienced three years with sustained viral suppression. Patients were categorized according to CD4 cell count after the three years suppressed period (≤ 200 cells/μL; immunological non-responders (INRs), >200 cells/μL; immunological responders (IRs)). We used logistic regression and Kaplan-Meier analysis to estimated risk factors and mortality for INRs compared to IRs., Results: We identified 55 INRs and 236 IRs. In adjusted analysis age > 40 years and > one year from first CD4 cell count ≤ 200 cells/μL to start of the virologically suppressed period were associated with increased risk of INR. INRs had substantially higher mortality compared to IRs. The excess mortality was mainly seen in the INR group with > one year of immunological suppression prior to viral suppression and injection drug users (IDUs)., Conclusion: Age and prolonged periods of immune deficiency prior to successful HAART are risk factors for incomplete CD4 cell recovery. INRs have substantially increased long-term mortality mainly associated with prolonged immunological suppression prior to viral suppression and IDU.
Published: 2010
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9. Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years.

Author: Lodwick R, Costagliola D, Reiss P, Torti C, Teira R, Dorrucci M, Ledergerber B, Mocroft A, Podzamczer D, Cozzi-Lepri A, Obel N, Masquelier B, Staszewski S, García F, De Wit S, Castagna A, Antinori A, Judd A, Ghosn J, Touloumi G, Mussini C, Duval X, Ramos J, Meyer L, Warsawski J, Thorne C, Masip J, Pérez-Hoyos S, Pillay D, van Sighem A, Lo Caputo S, Günthard H, Paredes R, De Luca A, Paraskevis D, Fabre-Colin C, Kjaer J, Chêne G, Lundgren JD, and Phillips AN
Subjects: Adolescent, Adult, Europe, Female, HIV Protease Inhibitors therapeutic use, Humans, Kaplan-Meier Estimate, Life Expectancy, Male, Middle Aged, Proportional Hazards Models, Reverse Transcriptase Inhibitors therapeutic use, Ritonavir therapeutic use, Treatment Failure, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Viral Load drug effects
Abstract: Background: Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades., Methods: We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed., Results: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF., Conclusions: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.
Published: 2010
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10. The insufficient suppression of viral load by saquinavir hard gel is reversible: a retrospective cohort study.

Author: Jensen-Fangel S, Kirk O, Blaxhult A, Gerstoft J, Pedersen C, Black FT, Lundgren JD, and Obel N
Subjects: Adult, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Capsules administration & dosage, Cohort Studies, Drug Therapy, Combination, Female, Gelatin, HIV Infections immunology, HIV Infections virology, HIV-1 physiology, Humans, Lamivudine therapeutic use, Male, RNA, Viral blood, Retrospective Studies, Reverse Transcriptase Inhibitors therapeutic use, Zidovudine therapeutic use, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, Saquinavir therapeutic use, Viral Load
Abstract: Purpose: To assess the effect of changing antiretroviral therapy in patients initially treated with saquinavir hard gel capsule (hgc)., Method: A retrospective cohort study comparing the virological and immunological responses in antiretroviral-naïve patients initially treated with a regimen of saquinavir-hgc, zidovudine, and lamivudine, with patients receiving either ritonavir or indinavir on a background of zidovudine and lamivudine., Results: Twenty-nine patients starting with saquinavir-hgc as the protease inhibitor (PI) component were compared to 58 patients starting with ritonavir (n = 16) or indinavir (n = 42). Median follow-up time was 30 and 33 months, respectively. Twelve, 18, 24, and 30 months after starting a regimen including saquinavir-hgc, 72%, 50%, 4%, and 0% of patients still received this PI. At these time points, 35%, 24%, 59%, and 74% of the patients in the saquinavir group obtained an HIV-RNA <500 copies/mL compared to 76%, 72%, 66%, and 65% in the indinavir/ritonavir group. No significant difference in CD4 count between the two groups was observed., Conclusion: We found that saquinavir-hgc, in combination with nucleoside reverse transcriptase inhibitors, suppressed viral load insufficiently in HIV patients naïve to antiretroviral therapy. However, the suboptimal effect of saquinavir-hgc seems reversible after optimizing the antiretroviral regimen, at least for the short term.
Published: 2001
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11. The Incidence of AIDS-Defining Illnesses at a Current CD4 Count ≥200 Cells/μL in the Post—Combination Antiretroviral Therapy Era

Author: Opportunistic Infections Working Group on behalf of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCOORD, Mocroft, A., Furrer, H. J., Miro, J. M., Reiss, P., Mussini, C., Kirk, O., Abgrall, S., Ayayi, S., Bartmeyer, B., Braun, D., Castagna, A., Monforte, A. d'Arminio, Gazzard, B., Gutierrez, F., Hurtado, I., Jansen, K., Meyer, L., Muñoz, P., Obel, N., Soler-Palacin, P., Papadopoulos, A., Raffi, F., Ramos, J. T., Rockstroh, J. K., Salmon, D., Torti, C., Warszawski, J., de Wit, S., Zangerle, R., Fabre-Colin, C., Kjaer, J., Chene, G., Grarup, J., and Lundgren, J. D.
Published: 2013
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12. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Author: Atkinson, A., Miro, J. M., Mocroft, A., Reiss, P., Kirk, O., Morlat, P., Ghosn, J., Stephan, C., Mussini, C., Antoniadou, A., Doerholt, K., Girardi, E., De Wit, S., Kraus, D., Zwahlen, M., Furrer, H., Castagna, A., Fatkenheuer, G., Raben, D., Teira, R., Zangerle, R., Judd, A., Touloumi, G., Warszawski, J., Meyer, L., Dabis, F., Krause, M. M., Leport, C., Wittkop, L., Wit, F., Prins, M., Bucher, H., Gibb, D., Del Amo, J., Obel, N., Thorne, C., Perez-Hoyos, S., Hamouda, O., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., d'Arminio Monforte, A., Brockmeyer, N., Prieto, L., Conejo, P. R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Garrido, M., Haerry, D., Costagliola, D., d'Arminio-Monforte, A., del Amo, J., Chene, G., Barger, D., Schwimmer, C., Termote, M., Frederiksen, C. M., Brandt, R. S., Berenguer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Smit, C., Sterne, J., Thiebaut, R., Wqetu, C., van der Valk, M., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Atkinson, A, Miro, J, Mocroft, A, Reiss, P, Kirk, O, Morlat, P, Ghosn, J, Stephan, C, Mussini, C, Antoniadou, A, Doerholt, K, Girardi, E, De Wit, S, Kraus, D, Zwahlen, M, Furrer, H, Castagna, A, Fatkenheuer, G, Raben, D, Teira, R, Zangerle, R, Judd, A, Touloumi, G, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Leport, C, Wittkop, L, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Obel, N, Thorne, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Casabona, J, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Garrido, M, Haerry, D, Costagliola, D, d'Arminio-Monforte, A, del Amo, J, Chene, G, Barger, D, Schwimmer, C, Termote, M, Frederiksen, C, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Wqetu, C, and van der Valk, M
Subjects: Adult, medicine.medical_specialty, Adolescent, opportunistic infection, Population, Human immunodeficiency virus (HIV), HIV Infections, 610 Medicine & health, Pneumocystis carinii, medicine.disease_cause, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, Epidemiology, medicine, Humans, Opportunistic infections, Viremia, 030212 general & internal medicine, education, Research Articles, education.field_of_study, 030505 public health, business.industry, Pneumonia, Pneumocystis, Incidence (epidemiology), prophylaxi, Pneumocystis jirovecii Pneumonia, Public Health, Environmental and Occupational Health, opportunistic infections, Pneumocystis jirovecii pneumonia, CD4 Lymphocyte Count, 3. Good health, Discontinuation, Europe, Infectious Diseases, Cohort, Infeccions per VIH, prophylaxis, 0305 other medical science, business, Viral load, Infeccions oportunistes, Research Article, HIV infections
Abstract: Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. Keywords: opportunistic infections; Pneumocystis jirovecii pneumonia; prophylaxis
Published: 2021

13. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

Author: Judd, A, Lodwick, R, Noguera‐Julian, A, Gibb, DM, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi‐Lepri, A, García, F, Brockmeyer, NH, Warszawski, J, Gonzalez‐Tome, MI, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, MA, Chene, G, Phillips, A, Mary Krause, Murielle, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Amo, Julia Del, Thorne, Claire, Kirk, Ole, Pérez‐Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Rojo, Pablo, Soriano‐Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Teira, Ramon, Garrido, Myriam, Haerry, David, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Frederiksen, Casper M., Friis‐Møller, Nina, Kjaer, Jesper, Salbøl Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Davies, Mary‐Anne, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, van der Valk, Marc, Wyss, Natasha, The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, APH - Global Health, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord., [Judd,A, Gibb,DM] MRC Clinical Trials Unit, University College London, London, UK. [ Lodwick,R, Sabin,C, Mocroft,A, Cozzi-Lepri,A, Phillips,A] Department of Infection and Population Health, University College London, London, UK. [Noguera-Julian,A] Institut de Recerca Pedi atrica Hospital Sant Joan de Deu, Barcelona, Spain. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiologıa y Salud Publica Ciberesp, Barcelona, Spain. [Butler,K] Department of Infectious Diseases and Immunology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland. [Costagliola,D] INSERM, UPMC Univ Paris 06, Institut Pierre Louis d’epidemiologie et de Sante Publique (IPLESP UMRS 1136), Sorbonne Universites, Paris, France. [van Sighem,A] Stichting HIV Monitoring, Amsterdam, The Netherlands. [Ledergerber,B] Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. [Torti,C] Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy. [Podzamczer,D[ HUV and STD Unit, Infectious Diseases Service, Hospital Universitari de Bellvitge. L’Hospitalet, Barcelona, Spain. [Dorrucci,M] Istituto Superiore di Sanit a, Rome, Italy. [De Wit,S] Departement of Infectious Diseases, Centre Hospitalier Saint-Pierre, Universite Libre de Bruxelles, Brussels, Belgium. [Obel,N] Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. [Dabis,F, Chene,D] NSERM U1219 – Centre Inserm Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. ISPED, Centre INSERM U1219-Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. [Garcia,F] Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigacion Biosanitaria ibs.Granada, Granada, Spain. [Brockmeyer,NH] Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany. [Warszawski,J] INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France. [Gonzalez-Tome,MI] HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. [Mussini,C] Infectious Diseases Clinics, University Hospital, Modena, Italy. [Touloumi,G] Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece. [Zangerle,R] Medical University Innsbruck, Innsbruck, Austria. [Ghosn,J] EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France. [Castagna,A] San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy. [Fätkenheuer,G] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. [Stephan,C] Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. [Meyer,L] NSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France. AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France. [Campbell,MA] Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark. [Chene,G]. CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France., Financial disclosure: The PLATO II project is funded by the UK Medical Research Council (award G0700832). The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), France, the HIV Monitoring Foundation, The Netherlands, and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The group has also received project-specific funding from the UK Medical Research Council and the Swiss Bridge Foundation., Judd, A, Lodwick, R, Noguera-Julian, A, Gibb, D, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi-Lepri, A, García, F, Brockmeyer, N, Warszawski, J, Gonzalez-Tome, M, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, M, Chene, G, Phillips, A, Puoti, M, Goethe-Universität Frankfurt am Main, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Copenhagen = Københavns Universitet (UCPH), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, University College of London [London] (UCL), Universitat Autònoma de Barcelona (UAB), Hospital Sant Joan de Déu [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Our Lady's Children's Hospital Crumlin (OLCHC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University hospital of Zurich [Zurich], Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Istituto Superiore di Sanita [Rome], Université libre de Bruxelles (ULB), Copenhagen University Hospital, Universidad de Granada = University of Granada (UGR), Ruhr-Universität Bochum [Bochum], Hospital Universitario 12 de Octubre [Madrid], Azienda Ospedaleria Universitaria di Modena, National and Kapodistrian University of Athens (NKUA), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University Hospital of Cologne [Cologne], HAL-SU, Gestionnaire, and The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord
Subjects: Male, HIV Infections, Pharmacologie, Santé publique, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual Behavior::Sexuality::Heterosexuality [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pharmacology (medical), Inhibidores de proteasas, Young adult, Europe, perinatal HIV infection, virological failure, young people, Adolescent, Adult, Anti-Retroviral Agents, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Time Factors, Treatment Failure, Young Adult, Drug Resistance, Viral, Population Groups, Pathologie maladies infectieuses, ComputingMilieux_MISCELLANEOUS, Adolescente, ADN polimerasa dirigida por ADN, Original Research, Health Policy, Enfermedades transmisibles, 3. Good health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], G0700832, Young people, Viral load, Human, Factores de riesgo, medicine.medical_specialty, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], 03 medical and health sciences, Virological failure, Recién nacido, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], Heterosexualidad, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Communicable Diseases [Medical Subject Headings], Perinatal HIV infection, RCUK, medicine.disease, Infecciones por VIH, Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Observational study, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], 0301 basic medicine, Pediatrics, Science et gestion hospitalières, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Anti-Retroviral Agents/therapeutic use, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Interquartile range, Epidemiology, HIV Infection, 030212 general & internal medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adulto, MRC, Infectious Diseases, Niño, Europa, VIH-1, Population Group, Time Factor, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Acquired immunodeficiency syndrome (AIDS), medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections::Acquired Immunodeficiency Syndrome [Medical Subject Headings], Persons::Persons::Age Groups::Child [Medical Subject Headings], ddc:610, Intervalos de confianza, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Inhibidores de la transcriptasa inversa, Confidence interval, Carga viral, Fármacos anti-VIH, Anti-Retroviral Agent, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published
Published: 2017

14. CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies

Author: Caby, F., Guiguet, M., Weiss, L., Winston, A. d., Miro, J. M., Konopnicki, D., Le Moing, V., Bonnet, F. h., Reiss, P., Mussini, C., Poizot-Martin, I., Taylor, N. l., Skoutelis, A., Meyer, L., Goujard, C., Bartmeyer, B., Boesecke, C., Antinori, A., Quiros-Roldan, E., Wittkop, L., Frederiksen, C., Castagna, A., Thurnheer, M. C., Svedhem, V., Jose, S., Costagliola, D., Mary-Krause, M., Grabar, S., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Dabis, F., Krause, M. M., Ghosn, J., Leport, C., Wit, F., Prins, M., Bucher, H., Gibb, D., Fätkenheuer, G., Del Amo, J., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Pérez-Hoyos, S., Hamouda, O., Chkhartishvili, N., Noguera-Julian, A., Monforte, A. D., Brockmeyer, N., Prieto, L., Conejo, P. R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., Miró, J. M., Konopnick, D., Goetghebuer, T., Sönnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Victor Dupouy, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, University of Barcelona, Université libre de Bruxelles (ULB), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], University of Amsterdam [Amsterdam] (UvA), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Evangelismos Athens General Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Bicêtre, Robert Koch Institute [Berlin] (RKI), University Hospital Bonn, National Institute for Infectious Diseases 'Lazzaro Spallanzani', Università degli Studi di Brescia = University of Brescia (UniBs), Team MORPH3EUS (INSERM U1219 - UB - ISPED), University of Copenhagen = Københavns Universitet (UCPH), IRCCS Ospedale San Raffaele [Milan, Italy], Bern University Hospital [Berne] (Inselspital), Karolinska Institutet [Stockholm], Public Health England [London], Hôpital Cochin [AP-HP], Agence Nationale de Recherches sur le Sida et les Hépatites Virales, (CD4/CD8 ratio and cancer risk) project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord: Ali Judd, Robert Zangerle, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Linda Wittkop, Peter Reiss, Ferdinand Wit, Maria Prins, Heiner Bucher, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Osamah Hamouda, Barbara Bartmeyer, Nikoloz Chkhartishvili, Antoni Noguera-Julian, Andrea Antinori, Antonella d'Arminio Monforte, Norbert Brockmeyer, Luis Prieto, Pablo Rojo Conejo, Antoni Soriano-Arandes, Manuel Battegay, Roger Kouyos, Cristina Mussini, Jordi Casabona, Jose M Miró, Antonella Castagna, Deborah Konopnick, Tessa Goetghebuer, Anders Sönnerborg, Carlo Torti, Caroline Sabin, Ramon Teira, Myriam Garrido, David Haerry, European Project: 287519, European Project: 260694,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROCOORD(2011), Admin, Oskar, European Union Seventh Framework Programme - 287519 - INCOMING, European Network of HIV/AIDS Cohort Studies to Coordinate at European and International Level Clinical Research on HIV/AIDS - EUROCOORD - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 260694 - VALID, Caby, Fabienne, Guiguet, Marguerite, Weiss, Laurence, Winston, Alan, Miro, Jose M, Konopnicki, Deborah, Le Moing, Vincent, Bonnet, Fabrice, Reiss, Peter, Mussini, Cristina, Poizot-Martin, Isabelle, Taylor, Ninon, Skoutelis, Athanasio, Meyer, Laurence, Goujard, Cécile, Bartmeyer, Barbara, Boesecke, Christoph, Antinori, Andrea, Quiros-Roldan, Eugenia, Wittkop, Linda, Frederiksen, Casper, Castagna, Antonella, Thurnheer, Maria Christine, Svedhem, Veronica, Jose, Sophie, Costagliola, Dominique, Mary-Krause, Murielle, Grabar, Sophie, Global Health, Infectious diseases, AII - Infectious diseases, and APH - Aging & Later Life
Subjects: CD4/CD8 ratio, CD8 T-cells, Kaposi sarcoma, efficient cART, non-Hodgkin lymphoma, 0301 basic medicine, Microbiology (medical), Lymphoma, [SDV]Life Sciences [q-bio], 030106 microbiology, CD4-CD8 Ratio, Non-Hodgkin, HIV Infections, Kaposi, Efficient cART, Drug resistance, HIV superinfection, CD8-Positive T-Lymphocytes, medicine.disease_cause, Men who have sex with men, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, CD4 Lymphocyte Count, HIV, Humans, Incidence, Risk Factors, Lymphoma, Non-Hodgkin, Sarcoma, Kaposi, immune system diseases, Medicine, 030212 general & internal medicine, Non-Hodgkin lymphoma, Transmission (medicine), business.industry, Sarcoma, Resistance mutation, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Superinfection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load, HIV drug resistance, Demography
Abstract: BackgroundA persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.MethodsPLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.ResultsWe included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).ConclusionsLow CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
Published: 2021

15. Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

Author: Monge, S., Mocroft, A., Sabin, A., Touloumi, G., Sighem, A., Abgrall, S., Dray-Spira, R., Spire, B., Castagna, A., Mussini, C., Zangerle, R., Hessamfar, M., Anderson, J., Hamouda, O., Ehren, K., Obel, N., Kirk, O., Antinori, A., Girardi, E., Saracino, A., Calmy, A., Wit, S., Wittkop, L., Bucher, C., Montoliu, A., Raben, D., Prins, M., Meyer, L., Chene, G., Burns, F., Amo, J., Judd, Ali, Zangerle, Robert, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Amo, Julia, Obel, Niels, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miró, Josem, Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Sabin, Caroline, Teira, Ramon, Garrido, Myriam, Haerry, David, Wit, Stéphane, Miró, M., Costagliola, Dominique, d'Arminio-Monforte, Antonella, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Miró, Jose, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Valk, Marc, Migrant Health Working Group for the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in, Eurocoord, Castagna, Antonella, AII - Infectious diseases, APH - Global Health, Infectious diseases, APH - Aging & Later Life, Global Health, Monge, S, Mocroft, A, Sabin, A, Touloumi, G, Sighem, A, Abgrall, S, Dray-Spira, R, Spire, B, Castagna, A, Mussini, C, Zangerle, R, Hessamfar, M, Anderson, J, Hamouda, O, Ehren, K, Obel, N, Kirk, O, Antinori, A, Girardi, E, Saracino, A, Calmy, A, Wit, S, Wittkop, L, Bucher, C, Montoliu, A, Raben, D, Prins, M, Meyer, L, Chene, G, Burns, F, Amo, J, Judd, A, Warszawski, J, Dabis, F, Krause, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Bucher, H, Gibb, D, Fatkenheuer, G, Thorne, C, Stephan, C, Perez-Hoyos, S, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Miro, J, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Miro, M, Costagliola, D, d'Arminio-Monforte, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, and Valk, M
Subjects: Male, 0301 basic medicine, Latin Americans, HIV Infections, migrants, Anti-Retroviral Agents/therapeutic use, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Epidemiology, Pharmacology (medical), 030212 general & internal medicine, Immunovirological response, Young adult, ddc:616, Transients and Migrants, Health Policy, virus diseases, Middle Aged, Viral Load, 3. Good health, Europe, combination antiretroviral therapy, HIV, immunovirological response, sex, Infectious Diseases, Treatment Outcome, Anti-Retroviral Agents, RNA, Viral, Female, Sex, Viral load, Cohort study, Adult, Cart, Combination antiretroviral therapy, medicine.medical_specialty, Adolescent, HIV Infections/drug therapy, Young Adult, 03 medical and health sciences, Population Groups, medicine, Humans, RNA, Viral/blood, Aged, business.industry, Migrant, 030112 virology, Confidence interval, CD4 Lymphocyte Count, migrant, Institutional repository, Immunology, business, Demography
Abstract: Objectives: The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004-2013. Methods: Migrants were defined as those with geographical origin (GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB) and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios (sHRs) were used for time to virological response (VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements < 400 HIV-1 RNA copies/ml). Results: Of 32 817 individuals, 25 799 (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9% in men and 63.3% in women). Migrant men and women from SSA started at lower CD4 cell counts than NAT individuals, which remained lower over time. VR was â¥ 85% at 12 months for all groups except CRB women (77.7%). Compared with NAT men and women, lower VR was experienced by NAME [sHR 0.91; 95% confidence interval (CI) 0.86-0.97] and SSA (sHR 0.88; 95% CI 0.82-0.95) men and CRB (sHR 0.77; 85% CI 0.67-0.89) women, respectively. Conclusions: Immunovirological response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need.
Published: 2018

16. Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

Author: Rohner E., Butikofer L., Schmidlin K., Sengayi M., Maskew M., Giddy J., Garone D., Moore R. D., D'Souza G., Goedert J. J., Achenbach C., Gill M. J., Kitahata M. M., Patel P., Silverberg M. J., Castilho J., McGowan C., Chen Y. -M. A., Law M., Taylor N., Paparizos V., Bonnet F., Verbon A., Fatkenheuer G., Post F. A., Sabin C., Mocroft A., Le Moing V., Dronda F., Obel N., Grabar S., Spagnuolo V., Antinori A., Quiros-Roldan E., Mussini C., Miro J. M., Meyer L., Hasse B., Konopnicki D., Roca B., Barger D., Raben D., Clifford G. M., Franceschi S., Brockmeyer N., Chakraborty R., Egger M., Bohlius J., Judd A., Zangerle R., Touloumi G., Warszawski J., Dabis F., Krause M. M., Ghosn J., Leport C., Wittkop L., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Del Amo J., Thorne C., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Monforte A. D., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Tookey P., Casabona J., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Teira R., Garrido M., Haerry D., De Wit S., Costagliola D., D'Arminio-Monforte A., Chene G., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Furrer H., Guiguet M., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Schomaker M., Smit C., Sterne J., Thiebaut R., Torti C., Van Der Valk M., Tanser F., Vinikoor M., MacEte E., Wood R., Stinson K., Fatti G., Phiri S., Chimbetete C., Malisita K., Eley B., Fritz C., Hobbins M., Kamenova K., Fox M., Prozesky H., Technau K., Sawry S., Benson C. A., Bosch R. J., Kirk G. D., Boswell S., Mayer K. H., Grasso C., Hogg R. S., Harrigan P. R., Montaner J. S. G., Yip B., Zhu J., Salters K., Gabler K., Buchacz K., Brooks J. T., Gebo K. A., Carey J. T., Rodriguez B., Horberg M. A., Thorne J. E., Rabkin C., Margolick J. B., Jacobson L. P., Klein M. B., Rourke S. B., Rachlis A. R., Cupido P., Hunter-Mellado R. F., Mayor A. M., Deeks S. G., Martin J. N., Saag M. S., Mugavero M. J., Willig J., Eron J. J., Napravnik S., Crane H. M., Drozd D. R., Haas D., Rebeiro P., Turner M., Bebawy S., Rogers B., Justice A. C., Dubrow R., Fiellin D., Gange S. J., Anastos K., Althoff K. N., McKaig R. G., Freeman A. M., Lent C., Van Rompaey S. E., Morton L., McReynolds J., Lober W. B., Abraham A. G., Lau B., Zhang J., Jing J., Modur S., Wong C., Hogan B., Desir F., Liu B., You B., Cahn P., Cesar C., Fink V., Sued O., Dell'Isola E., Perez H., Valiente J., Yamamoto C., Grinsztejn B., Veloso V., Luz P., De Boni R., Wagner S. C., Friedman R., Moreira R., Pinto J., Ferreira F., Maia M., De Menezes Succi R. C., MacHado D. M., De Fatima Barbosa Gouvea A., Wolff M., Cortes C., Rodriguez M. F., Allendes G., Pape J. W., Rouzier V., Marcelin A., Perodin C., Luque M. T., Padgett D., Madero J. S., Ramirez B. C., Belaunzaran P., Vega Y. C., Gotuzzo E., Mejia F., Carriquiry G., McGowan C. C., Shepherd B. E., Sterling T., Jayathilake K., Person A. K., Rebeiro P. F., Giganti M., Duda S. N., Maruri F., Vansell H., Ly P. S., Khol V., Zhang F. J., Zhao H. X., Han N., Lee M. P., Li P. C. K., Lam W., Chan Y. T., Kumarasamy N., Saghayam S., Ezhilarasi C., Pujari S., Joshi K., Gaikwad S., Chitalikar A., Merati T. P., Wirawan D. N., Yuliana F., Yunihastuti E., Imran D., Widhani A., Tanuma J., Oka S., Nishijima T., Choi J. Y., Na S., Kim J. M., Sim B. L. H., Gani Y. M., David R., Kamarulzaman A., Syed Omar S. F., Ponnampalavanar S., Azwa I., Ditangco R., Uy E., Bantique R., Wong W. W., Ku W. W., Wu P. C., Ng O. T., Lim P. L., Lee L. S., Ohnmar P. S., Avihingsanon A., Gatechompol S., Phanuphak P., Phadungphon C., Kiertiburanakul S., Sungkanuparph S., Chumla L., Sanmeema N., Chaiwarith R., Sirisanthana T., Kotarathititum W., Praparattanapan J., Kantipong P., Kambua P., Ratanasuwan W., Sriondee R., Nguyen K. V., Bui H. V., Nguyen D. T. H., Nguyen D. T., Cuong D. D., An N. V., Luan N. T., Sohn A. H., Ross J. L., Petersen B., Cooper D. A., Law M. G., Jiamsakul A., Boettiger D. C., Ellis D., Bloch M., Agrawal S., Vincent T., Allen D., Smith D., Rankin A., Baker D., Templeton D. J., Jackson E., McCallum K., Ryder N., Sweeney G., Cooper D., Carr A., MacRae K., Hesse K., Finlayson R., Gupta S., Langton-Lockton J., Shakeshaft J., Brown K., Idle S., Arvela N., Varma R., Lu H., Couldwell D., Eswarappa S., Smith D. E., Furner V., Cabrera G., Fernando S., Cogle A., Lawrence C., Mulhall B., Boyd M., Petoumenos K., Puhr R., Huang R., Han A., Gunathilake M., Payne R., O'Sullivan M., Croydon A., Russell D., Cashman C., Roberts C., Sowden D., Taing K., Marshall P., Orth D., Youds D., Rowling D., Latch N., Warzywoda E., Dickson B., Donohue W., Moore R., Edwards S., Boyd S., Roth N. J., Lau H., Read T., Silvers J., Zeng W., Hoy J., Watson K., Bryant M., Price S., Woolley I., Giles M., Korman T., Williams J., Nolan D., Allen A., Guelfi G., Mills G., Wharry C., Raymond N., Bargh K., Templeton D., Medical Microbiology & Infectious Diseases, Global Health, Infectious diseases, APH - Aging & Later Life, AII - Infectious diseases, APH - Global Health, Graduate School, APH - Digital Health, APH - Personalized Medicine, Bohlius, Julia, Cohere In, Eurocoord, Castagna, Antonella, Rohner, E, Butikofer, L, Schmidlin, K, Sengayi, M, Maskew, M, Giddy, J, Garone, D, Moore, R, D'Souza, G, Goedert, J, Achenbach, C, Gill, M, Kitahata, M, Patel, P, Silverberg, M, Castilho, J, Mcgowan, C, Chen, Y, Law, M, Taylor, N, Paparizos, V, Bonnet, F, Verbon, A, Fatkenheuer, G, Post, F, Sabin, C, Mocroft, A, Le Moing, V, Dronda, F, Obel, N, Grabar, S, Spagnuolo, V, Antinori, A, Quiros-Roldan, E, Mussini, C, Miro, J, Meyer, L, Hasse, B, Konopnicki, D, Roca, B, Barger, D, Raben, D, Clifford, G, Franceschi, S, Brockmeyer, N, Chakraborty, R, Egger, M, Bohlius, J, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Dabis, F, Krause, M, Ghosn, J, Leport, C, Wittkop, L, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Thorne, C, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Monforte, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Teira, R, Garrido, M, Haerry, D, De Wit, S, Costagliola, D, D'Arminio-Monforte, A, Chene, G, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Furrer, H, Guiguet, M, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Torti, C, Van Der Valk, M, Tanser, F, Vinikoor, M, Macete, E, Wood, R, Stinson, K, Fatti, G, Phiri, S, Chimbetete, C, Malisita, K, Eley, B, Fritz, C, Hobbins, M, Kamenova, K, Fox, M, Prozesky, H, Technau, K, Sawry, S, Benson, C, Bosch, R, Kirk, G, Boswell, S, Mayer, K, Grasso, C, Hogg, R, Harrigan, P, Montaner, J, Yip, B, Zhu, J, Salters, K, Gabler, K, Buchacz, K, Brooks, J, Gebo, K, Carey, J, Rodriguez, B, Horberg, M, Thorne, J, Rabkin, C, Margolick, J, Jacobson, L, Klein, M, Rourke, S, Rachlis, A, Cupido, P, Hunter-Mellado, R, Mayor, A, Deeks, S, Martin, J, Saag, M, Mugavero, M, Willig, J, Eron, J, Napravnik, S, Crane, H, Drozd, D, Haas, D, Rebeiro, P, Turner, M, Bebawy, S, Rogers, B, Justice, A, Dubrow, R, Fiellin, D, Gange, S, Anastos, K, Althoff, K, Mckaig, R, Freeman, A, Lent, C, Van Rompaey, S, Morton, L, Mcreynolds, J, Lober, W, Abraham, A, Lau, B, Zhang, J, Jing, J, Modur, S, Wong, C, Hogan, B, Desir, F, Liu, B, You, B, Cahn, P, Cesar, C, Fink, V, Sued, O, Dell'Isola, E, Perez, H, Valiente, J, Yamamoto, C, Grinsztejn, B, Veloso, V, Luz, P, De Boni, R, Wagner, S, Friedman, R, Moreira, R, Pinto, J, Ferreira, F, Maia, M, De Menezes Succi, R, Machado, D, De Fatima Barbosa Gouvea, A, Wolff, M, Cortes, C, Rodriguez, M, Allendes, G, Pape, J, Rouzier, V, Marcelin, A, Perodin, C, Luque, M, Padgett, D, Madero, J, Ramirez, B, Belaunzaran, P, Vega, Y, Gotuzzo, E, Mejia, F, Carriquiry, G, Shepherd, B, Sterling, T, Jayathilake, K, Person, A, Giganti, M, Duda, S, Maruri, F, Vansell, H, Ly, P, Khol, V, Zhang, F, Zhao, H, Han, N, Lee, M, Li, P, Lam, W, Chan, Y, Kumarasamy, N, Saghayam, S, Ezhilarasi, C, Pujari, S, Joshi, K, Gaikwad, S, Chitalikar, A, Merati, T, Wirawan, D, Yuliana, F, Yunihastuti, E, Imran, D, Widhani, A, Tanuma, J, Oka, S, Nishijima, T, Choi, J, Na, S, Kim, J, Sim, B, Gani, Y, David, R, Kamarulzaman, A, Syed Omar, S, Ponnampalavanar, S, Azwa, I, Ditangco, R, Uy, E, Bantique, R, Wong, W, Ku, W, Wu, P, Ng, O, Lim, P, Lee, L, Ohnmar, P, Avihingsanon, A, Gatechompol, S, Phanuphak, P, Phadungphon, C, Kiertiburanakul, S, Sungkanuparph, S, Chumla, L, Sanmeema, N, Chaiwarith, R, Sirisanthana, T, Kotarathititum, W, Praparattanapan, J, Kantipong, P, Kambua, P, Ratanasuwan, W, Sriondee, R, Nguyen, K, Bui, H, Nguyen, D, Cuong, D, An, N, Luan, N, Sohn, A, Ross, J, Petersen, B, Cooper, D, Jiamsakul, A, Boettiger, D, Ellis, D, Bloch, M, Agrawal, S, Vincent, T, Allen, D, Smith, D, Rankin, A, Baker, D, Templeton, D, Jackson, E, Mccallum, K, Ryder, N, Sweeney, G, Carr, A, Macrae, K, Hesse, K, Finlayson, R, Gupta, S, Langton-Lockton, J, Shakeshaft, J, Brown, K, Idle, S, Arvela, N, Varma, R, Lu, H, Couldwell, D, Eswarappa, S, Furner, V, Cabrera, G, Fernando, S, Cogle, A, Lawrence, C, Mulhall, B, Boyd, M, Petoumenos, K, Puhr, R, Huang, R, Han, A, Gunathilake, M, Payne, R, O'Sullivan, M, Croydon, A, Russell, D, Cashman, C, Roberts, C, Sowden, D, Taing, K, Marshall, P, Orth, D, Youds, D, Rowling, D, Latch, N, Warzywoda, E, Dickson, B, Donohue, W, Edwards, S, Boyd, S, Roth, N, Lau, H, Read, T, Silvers, J, Zeng, W, Hoy, J, Watson, K, Bryant, M, Price, S, Woolley, I, Giles, M, Korman, T, Williams, J, Nolan, D, Allen, A, Guelfi, G, Mills, G, Wharry, C, Raymond, N, and Bargh, K
Subjects: Male, viruses, HIV Infections, Men who have sex with men, Cohort Studies, 0302 clinical medicine, Risk Factors, Antiretroviral therapy, Cohort study, HIV, Kaposi sarcoma, Adolescent, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Female, HIV-1, Humans, Middle Aged, Sarcoma, Kaposi, Viral Load, Young Adult, 030212 general & internal medicine, Articles and Commentaries, Incidence (epidemiology), Hazard ratio, virus diseases, Sarcoma, 3. Good health, Infectious Diseases, 030220 oncology & carcinogenesis, Cohort, Coinfection, Microbiology (medical), antiretroviral therapy, 610 Medicine & health, Kaposi, 03 medical and health sciences, SDG 3 - Good Health and Well-being, 360 Social problems & social services, medicine, cohort study, business.industry, medicine.disease, Confidence interval, business, Demography
Abstract: Background We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results We included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were
Published: 2017

17. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients

Author: Bouteloup V., Sabin C., Mocroft A., Gras L., Pantazis N., Le Moing V., d'Arminio Monforte A., Mary-Krause M., Roca B., Miro J. M., Battegay M., Brockmeyer N., Berenguer J., Morlat P., Obel N., De Wit S., Fatkenheuer G., Zangerle R., Ghosn J., Perez-Hoyos S., Campbell M., Prins M., Chene G., Meyer L., Dorrucci M., Torti C., Thiebaut R., Touloumi G., Warszawski J., Dabis F., Leport C., Wittkop L., Reiss P., Wit F., Bucher H., Gibb D., Amo J. D., Thorne C., Kirk O., Stephan C., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., Prieto L., Conejo P. R., Soriano-Arandes A., Rauch A., Mussini C., Tookey P., Casabona J., Castagna A., Deborah Konopnick, Goetghebuer T., Sonnerborg A., Teira R., Garrido M., Haerry D., Costagliola D., del Amo J., Raben D., Judd A., Barger D., Colin C., Schwimmer C., Termote M., Friis-Moller N., Kjaer J., Brandt R. S., Bohlius J., Cozzi-Lepri A., Davies M. -A., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Schomaker M., Smit C., Sterne J., van der Valk M., Wyss N., AII - Infectious diseases, APH - Global Health, Infectious diseases, APH - Aging & Later Life, Global Health, Bouteloup, V, Sabin, C, Mocroft, A, Gras, L, Pantazis, N, Le Moing, V, d'Arminio Monforte, A, Mary-Krause, M, Roca, B, Miro, Jm, Battegay, M, Brockmeyer, N, Berenguer, J, Morlat, P, Obel, N, De Wit, S, Fätkenheuer, G, Zangerle, R, Ghosn, J, Pérez-Hoyos, S, Campbell, M, Prins, M, Chêne, G, Dorrucci, M, Torti, C, Thiébaut, R, the Standard Reference Distribution of CD4 Response to HAART Project Team for the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in, Eurocoord, Castagna, Antonella, Miro, J, Fatkenheuer, G, Perez-Hoyos, S, Chene, G, Meyer, L, Thiebaut, R, Touloumi, G, Warszawski, J, Dabis, F, Leport, C, Wittkop, L, Reiss, P, Wit, F, Bucher, H, Gibb, D, Amo, J, Thorne, C, Kirk, O, Stephan, C, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Rauch, A, Mussini, C, Tookey, P, Casabona, J, Castagna, A, Deborah, K, Goetghebuer, T, Sonnerborg, A, Teira, R, Garrido, M, Haerry, D, Costagliola, D, del Amo, J, Raben, D, Judd, A, Barger, D, Colin, C, Schwimmer, C, Termote, M, Friis-Moller, N, Kjaer, J, Brandt, R, Bohlius, J, Cozzi-Lepri, A, Davies, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, van der Valk, M, Wyss, N, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Department of Infection and Population Health [London], University College of London [London] (UCL), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Department of Hygiene, Epidemiology and Medical Statistics [Athens], University of Athens Medical School [Athens], Université de Montpellier (UM), Università degli Studi di Milano [Milano] (UNIMI), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General De Castellon, Clinical and experimental neuroimmunology [IDIBAPS], Institut d'Investigacions Biomèdiques August Pi i Sunyer, University Hospital Basel [Basel], Ruhr-Universität Bochum [Bochum], Hospital General Universitario 'Gregorio Marañón' [Madrid], Hôpital Saint-André, University of Copenhagen = Københavns Universitet (KU), Université libre de Bruxelles (ULB), University Hospital of Cologne [Cologne], Universität Innsbruck [Innsbruck], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universitat Autònoma de Barcelona (UAB), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Istituto Superiore di Sanita [Rome], Università degli Studi 'Magna Graecia' di Catanzaro [Catanzaro, Italie] (UMG), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Milano = University of Milan (UNIMI), University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Superiore di Sanità (ISS), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École des Ponts ParisTech (ENPC)-École polytechnique (X)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), CRAHI-UPC, Edifici NEXUS 104-106, Calle Gran Capità 2-4, 08034 Barcelona, Spain, affiliation inconnue, Pork CRC Roseworthy, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Laboratoire Evolution, Génomes et Spéciation (LEGS), and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, Pediatrics, Percentile, longitudinal data, [SDV]Life Sciences [q-bio], CD4 response, HIV monitoring, antiretroviral treatment monitoring, longitudinal data, HIV Infections, Cohort Studies, 0302 clinical medicine, antiretroviral treatment monitoring, CD4 response, HIV monitoring, Adolescent, Adult, Aged, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Monitoring, Europe, Female, HIV-1, Humans, Middle Aged, Treatment Outcome, Viral Load, Young Adult, Interquartile range, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Epidemiology, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Health Policy, virus diseases, 3. Good health, Infectious Diseases, CD4-Positive T-Lymphocyte, Cohort, Viral load, Human, Cart, medicine.medical_specialty, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), medicine, business.industry, medicine.disease, 030112 virology, Antiretroviral therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Anti-Retroviral Agent, Cohort Studie, business
Abstract: Objectives: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. Methods: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged â¥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load â¤ 50 HIV-1 RNA copies/mL at 6 months (Â± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. Results: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/Î¼L. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/Î¼L. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of â¥ 100 cells/mL is generally required in order that patients stay âon trackâ (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Conclusions: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.
Published: 2017

18. Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

Author: Engsig, F. N., Zangerle, R., Katsarou, O., Dabis, F., Reiss, P., Gill, J., Porter, K., Sabin, C., Riordan, A., Fatkenheuer, G., Gutierrez, F., Raffi, F., Kirk, O., Mary-Krause, M., Stephan, C., de Olalla, P. G., Guest, J., Samji, H., Castagna, A., d'Arminio Monforte, A., Skaletz-Rorowski, A., Ramos, J., Lapadula, G., Mussini, C., Force, L., Meyer, L., Lampe, F., Boufassa, F., Bucher, H. C., De Wit, S., Burkholder, G. A., Teira, R., Justice, A. C., Sterling, T. R., M. Crane, H., Gerstoft, J., Grarup, J., May, M., Chene, G., Ingle, S. M., Sterne, J., Obel, N., Burkholder, G., Justice, A., R Sterling, T., Crane, H. M., Boulle, A., Brodt, H.-R., Casabona, J., Cavassini, M., Costagliola, D., D'Arminio Monforte, A., del Amo, J., Van Sighem, A., Hans-Ulrich Haerry, D., Hogg, R., Mocroft, A., Kitahata, M., Saag, M., Williams, M., Ingle, S., Touloumi, G., Warszawski, J., Krause, M. M., Ghosn, J., Leport, C., Wit, F., Prins, M., Gibb, D., Del Amo, J., Thorne, C., Perez-Hoyos, S., Hamouda, O., Gussenheimer-Bartmeyer, B., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Battegay, M., Rauch, A., Tookey, P., Miro, J. M., de Wit, S., Goetghebuer, T., Torti, C., Garrido, M., Judd, A., Conejo, P. R., Haerry, D., Weller, I., d'Arminio-Monforte, A., Colin, C., Schwimmer, C., Termote, M., Kjaer, J., Campbell, M., Raben, D., Bohlius, J., Bouteloup, V., Bucher, H., Cozzi-Lepri, A., Dorrucci, M., Egger, M., Engsig, F., Furrer, H., Lambotte, O., Lewden, C., Lodi, S., Lodwick, R., Matheron, S., Miro, J., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Reekie, J., Scherrer, A., Smit, C., Thiebaut, R., Wittkop, L., 2nd Blood Transfusion Center and Hemophilia Center, 'Laiko' General Hospital, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Micro et Nano Technologies (OMNT - UMS 2920), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Southern Alberta Clinic, Research Department of Infection and Population Health [London], University College of London [London] (UCL), Equipe Perception et design sonores, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), Equipe Interactions musicales temps-réel, Maladies infectieuses et tropicales, Université Pierre et Marie Curie - Paris 6 (UPMC), Institute of Biology, Neuchatel, Université de Neuchâtel (UNINE), School of Psychology, St Andrews, University of St Andrews [Scotland], Infectious Diseases, San Raffaele Scientific Institute, EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Laboratory of Inorganic Chemistry, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Princeton University, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Population Sciences, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Paläontologisches Institut und Museum, Universität Zürich [Zürich] (UZH), Laboratory, GD Deventer, Rigshospitalet [Copenhagen], Department of Social Medicine, University of Bristol [Bristol], Department of Infectious Diseases, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), School of Psychology and Neuroscience [University of St. Andrews], Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 1 Panthéon-Sorbonne (UP1), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Zürich [Zürich] = University of Zurich (UZH), Royal GD [Deventer], Copenhagen University Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Engsig, F. N., Zangerle, R., Katsarou, O., Dabis, F., Reiss, P., Gill, J., Porter, K., Sabin, C., Riordan, A., Fatkenheuer, G., Gutierrez, F., Raffi, F., Kirk, O., Mary-Krause, M., Stephan, C., De Olalla, P. G., Guest, J., Samji, H., Castagna, A., D'arminio Monforte, A., Skaletz-Rorowski, A., Ramos, J., Lapadula, G., Mussini, C., Force, L., Meyer, L., Lampe, F., Boufassa, F., Bucher, H. C., De Wit, S., Burkholder, G. A., Teira, R., Justice, A. C., Sterling, T. R., M. Crane, H., Gerstoft, J., Grarup, J., May, M., Chene, G., Ingle, S. M., Sterne, J., Obel, N., Engsig, F, Zangerle, R, Katsarou, O, Dabis, F, Reiss, P, Gill, J, Porter, K, Sabin, C, Riordan, A, Fatkenheuer, G, Gutierrez, F, Raffi, F, Kirk, O, Mary-Krause, M, Stephan, C, De Olalla, P, Guest, J, Samji, H, Castagna, A, D'arminio Monforte, A, Skaletz-Rorowski, A, Ramos, J, Lapadula, G, Mussini, C, Force, L, Meyer, L, Lampe, F, Boufassa, F, Bucher, H, De Wit, S, Burkholder, G, Teira, R, Justice, A, Sterling, T, M. Crane, H, Gerstoft, J, Grarup, J, May, M, Chene, G, Ingle, S, Sterne, J, Obel, N, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, and Infectious diseases
Subjects: Male, Oncology, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], HIV Infections, MESH: Logistic Models, Cohort Studies, MESH: Cause of Death, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Cause of Death, Medicine, HIV Infection, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Cohort Studies, Immunodeficiency, Cause of death, 0303 health sciences, MESH: Middle Aged, Hazard ratio, MESH: HIV Infections, Middle Aged, Viral Load, 3. Good health, Infectious Diseases, MESH: Substance-Related Disorders, HIV/AIDS, Female, MESH: Viral Load, Viral load, MESH: Heterosexuality, Human, Adult, Microbiology (medical), Cart, medicine.medical_specialty, Logistic Model, Anti-HIV Agents, Substance-Related Disorders, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Humans, sustained viral suppression, Heterosexuality, 030304 developmental biology, MESH: Humans, business.industry, Proportional hazards model, Risk Factor, Anti-HIV Agent, HIV, MESH: Adult, Substance-Related Disorder, medicine.disease, mortality, CD4 cell recovery, Confidence interval, MESH: Male, CD4 Lymphocyte Count, Logistic Models, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort Studie, business, MESH: Female
Abstract: Background. Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/μL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.Methods. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/μL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/μL) and Cox regression to identify associations with mortality.Results. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/μL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/μL. Individuals with CD4 ≤200 cells/μL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/μL. The increased mortality was seen across different patient groups and for all causes of death.Conclusions. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/μL have substantially increased long-term mortality. © The Author 2014.
Published: 2014

19. Predictors of CD4(+) T-cell counts of HIV type 1-infected persons after virologic failure of all 3 original antiretroviral drug classes

Author: Audelin, A., Castagna, A., Costagliola, D., Cozzi-Lepri, A., De Luca, A., De Wit, S., de Wolf, F., Dorrucci, M., Duval, X., Fatkenheuer, G., Garcia, F., Ghosn, J., Gunthard, H., Jansen, K., Judd, A., Ledergerber, B., Lo Caputo, S., Lodwick, R., Masquelier, B., Meyer, L., Mocroft, A., Mussini, C., Noguera-Julian, A., Obel, N., Paraskevis, D., Paredes, R., Perez-Hoyos, S., Phillips, A., Pillay, D., Podzamczer, D., Ramos, J. T., Stephan, C., Tookey, P. A., Torti, C., Touloumi, G., van Sighem, A., Warsawski, J., Zangerle, R., Warszawski, J., Dabis, F., Krause, M. M., Leport, C., Reiss, P., Prins, M., Bucher, H., Sabin, C., Gibb, D., Del Amo, J., Thorne, C., Kirk, O., Antinori, A., d'Arminio Monforte, A., Brockmeyer, N., Ramos, J., Battegay, M., Rauch, A., Tookey, P., Casabona, J., Miro, J. M., de Wit, S., Goetghebuer, T., Teira, R., Garrido, M., Haerry, D., Weller, I., d'Arminio-Monforte, A., Grarup, J., Chene, G., Bohlius, J., Bouteloup, V., Egger, M., Engsig, F., Furrer, H., Lambotte, O., Lewden, C., Matheron, S., Miro, J., Puoti, M., Reekie, J., Scherrer, A., Smit, C., Sterne, J., Thiebaut, R., von Wyl, V., Wittkop, L., Ledergerber, Bruno, Cohere, Cohort, Castagna, Antonella, Other departments, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Global Health, and Infectious diseases
Subjects: Adult, Male, medicine.medical_specialty, Efavirenz, Infectious Disease, HIV Infections, Settore MED/17 - MALATTIE INFETTIVE, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, antiretroviral agent, Internal medicine, Medicine, Immunology and Allergy, Humans, Protease inhibitor (pharmacology), HIV Infection, 030212 general & internal medicine, Anti-Retroviral Agents, CD4 Lymphocyte Count, Female, Middle Aged, Treatment Failure, Viral Load, Generalized estimating equation, HIV cohort study, business.industry, CD4 lymphocyte count, Raltegravir, Confidence interval, 3. Good health, VIROLOGIC FAILURE, Infectious Diseases, chemistry, 030220 oncology & carcinogenesis, Immunology, Cohort, triple-class virologic failure, HIV-1, Anti-Retroviral Agent, business, Viral load, medicine.drug, Human
Abstract: Background. Low CD4+ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4+ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4+ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4+ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/Î¼L [95% confidence interval CI, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/Î¼L [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of 5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and 186 cells/Î¼L, respectively (P
Published: 2013

20. The incidence of AIDS-defining illnesses at a current CD4 count ≥200 cells/μL in the post-combination antiretroviral therapy era

Author: Mocroft, A., Furrer, H. J., Miro, J. M., Reiss, P., Mussini, C., Kirk, O., Abgrall, S., Ayayi, S., Bartmeyer, B., Braun, D., Castagna, A., d'Arminio Monforte, A., Gazzard, B., Gutierrez, F., Hurtado, I., Jansen, K., Meyer, L., Munoz, P., Obel, N., Soler Palacin, P., Papadopoulos, A., Raffi, F., Ramos, J. T., Rockstroh, J. K., Salmon, D., Torti, Carlo, Warszawski, J., de Wit, S., Zangerle, R., Fabre Colin, C., Kjaer, J., Chene, G., Grarup, J., Lundgren, J. D., Furrer, H., Rockstroh, J., Lundgren, J., Miiro, J., Palacin, P. S., Torti, C., Ramos, J., Judd, A., Haerry, D., Weller, I., Casabona, J., Costagliola, D., Battegay, M., Prins, M., de Wolf, F., Colin, C., Schwimmer, C., Touzeau, G., Campbell, M., Bohlius, J., Bouteloup, V., Bucher, H., Cozzi Lepri, A., Dabis, F., Dorrucci, M., Egger, M., Engsig, F., Lambotte, O., Lewden, C., Lodwick, R., Matheron, S., Miro, J., Paredes, R., Phillips, A., Puoti, M., Reekie, J., Sabin, C., Scherrer, A., Smit, C., Sterne, J., Thiebaut, R., Thorne, C., von Wyl, V., Wittkop, L., Young, J., Mocroft, A., Furrer, H. J., Miro, J. M., Reiss, P., Mussini, C., Kirk, O., Abgrall, S., Ayayi, S., Bartmeyer, B., Braun, D., Castagna, A., D'Arminio Monforte, A., Gazzard, B., Gutierrez, F., Hurtado, I., Jansen, K., Meyer, L., Munoz, P., Obel, N., Soler-Palacin, P., Papadopoulos, A., Raffi, F., Ramos, J. T., Rockstroh, J. K., Salmon, D., Torti, C., Warszawski, J., De Wit, S., Zangerle, R., Fabre-Colin, C., Kjaer, J., Chene, G., Grarup, J., Lundgren, J. D., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, University of Zurich, and Mocroft, A
Subjects: Microbiology (medical), Adult, CD4-Positive T-Lymphocytes, Male, medicine.medical_specialty, Virologic suppression, AIDS defining illnesses, Human immunodeficiency virus (HIV), 610 Medicine & health, HIV Infections, Rate ratio, medicine.disease_cause, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, Cohort Studies, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), 360 Social problems & social services, Internal medicine, medicine, CART, Humans, 030212 general & internal medicine, Poisson regression, Poisson Distribution, 0303 health sciences, 030306 microbiology, business.industry, Incidence (epidemiology), Incidence, CD4, cART, immune reconstitution, virologic suppression, Anti-Retroviral Agents, CD4 Lymphocyte Count, Europe, Female, 2725 Infectious Diseases, Immune reconstitution, medicine.disease, Antiretroviral therapy, Confidence interval, 3. Good health, Infectious Diseases, Immunology, symbols, business, Viral load
Abstract: Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 μL between 1998 and 2010 were included. Incidence rates (per 1000 personyears of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/μL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/μL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/μL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/μL. Persons with a current CD4 of 500-749 cells/μL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/μL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/μL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/μL to 750-999 cells/μL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/μL compared to those with a CD4 count of 750-999 cells/μL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/μL. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Published: 2013

21. Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study

Author: Castagliola, D, Ledergerber, B, Torti, Carlo, van Sighem, A, Podzamczer, D, Mocroft, A, Dorrucci, M, Masquelier, B, de Luca, A, Jansen, K, De Wit, S, Obel, N, Fätkenheuer, G, Touloumi, G, Mussini, C, Castagna, A, Stephan, C, Garcia, F, Zangerle, R, Duval, X, Pérez Hoyos, S, Meyer, L, Ghosn, J, Fabre Colin, C, Kjaer, J, Chene, G, Grarup, J, Costagliola, D, Lodwick, R, Phillips, A, Pursuing Later Treatment Option II project team, Observational HIV Epidemiological Research Europe Group, Costagliola, D, Lodwick, R, Ledergerber, B, Collaboration Of Observational Hiv Epidemiological Research Europe (COHERE) Grp, Castagna, Antonella, Other departments, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, and Infectious diseases
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Anti-HIV Agents, HIV-1, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections, Humans, Middle Aged, RNA, Viral, Regression Analysis, Retrospective Studies, Young Adult, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), RNA, Viral -- blood, Internal medicine, medicine, HIV, AIDS, viral load, Protease inhibitor (pharmacology), 030212 general & internal medicine, Poisson regression, Young adult, Pathologie maladies infectieuses, HIV Infections -- blood -- drug therapy -- virology, 0303 health sciences, 030306 microbiology, business.industry, Incidence (epidemiology), Retrospective cohort study, Sciences bio-médicales et agricoles, medicine.disease, 3. Good health, Infectious Diseases, Immunology, symbols, RNA, Viral, Anti-HIV Agents -- therapeutic use, business, Viral load, Cohort study
Abstract: Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09., info:eu-repo/semantics/published
Published: 2012

22. Risk of virus transmission from well-treated patients with HIV?

Author: Gerstoft, J., Mathiesen, L., Jens Lundgren, Nielsen, H. I., Pedersen, C., Obel, N., and Laursen, A.
Subjects: Risk Factors, Sexual Behavior, Communicable Disease Control, HIV Seropositivity, Humans, HIV Infections, Viral Load, Heterosexuality
Abstract: Udgivelsesdato: 2009-Mar-23
Published: 2009

23. Response to combination antiretroviral therapy: Variation by age

Author: Collaboration of Observational HIV Epidemiological Research Europe Study Group, Sabin, Ca, Smith, Cj, d'Arminio Monforte, A, Battegay, M, Gabiano, C, Galli, L, Geelen, S, Gibb, D, Guiguet, M, Judd, A, Leport, C, Dabis, F, Pantazis, N, Porter, K, Raffi, F, Thorne, C, Torti, C, Walker, S, Warszawski, J, Wintergerst, U, Chene, G, Lundgren, J., Collaborators: Weller, I, Costagliola, D, Ledergerber, B, Lundgren, J, Touloumi, G, Meyer, L, Krause, Mm, Goujard, C, de Wolf, F, Reiss, P, Dorrucci, M, Sabin, C, Del Amo, J, Obel, N, Mocroft, A, Kirk, O, Staszewski, S, Perez Hoyos, S, Almeda, J, Antinori, A, Monforte, Ad, Tovo, Pier Angelo, Salzberger, B, Fatkenheuer, G, Ramos, J, Mussini, C, Tookey, P, Casabona, J, Miro, Jm, Castagna, A, de Wit, S, Teira, R, Garrido, M, Dedes, N, Phillips, A, Furrer, H, Egger, M, Newell, Ml, Sterne, J, Telentie, A., Sabin Caroline, A., Smith Colette, J., Monforte A., D'Arminio, Battegay, Manuel, Gabiano, Clara, Galli, Luisa, Geelen, Sibyl, Gibb, Diana, Guiguet, Marguerite, Judd, Ali, Leport, Catherine, Dabis, Francoi, Pantazis, Niko, Porter, Kholoud, Raffi, Francoi, Thorne, Claire, Torti, Carlo, Walker, Sarah, Warszawski, Josiane, Wintergerst, Uwe, Chene, Genevieve, Lundgren, Jen, Weller, Ian, Costagliola, Dominique, Ledergerber, Bruno, Touloumi, Giota, Meyer, Laurence, Krause Murielle, Mary, Goujard, Cecile, de Wolf, Frank, Reiss, Peter, Dorrucci, Maria, Sabin, Caroline, Del Amo, Julia, Obel, Niel, Mocroft, Amanda, Kirk, Ole, Staszewski, Schlomo, Perez Hoyos, Santiago, Almeda, Jesu, Antinori, Andrea, Tovo Pier, Angelo, Salzberger, Bernd, Fatkenheuer, Gerd, Ramos, Jose, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miro Jose, M., Castagna, Antonella, de Wit, Stephane, Teira, Ramon, Garrido, Myriam, Dedes, Niko, Phillips, Andrew, Furrer, Hansjakob, Egger, Matthia, Newell Marie, Louise, Sterne, Jonathan, Telenti, Amalio, Other departments, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Infectious diseases
Subjects: Pediatrics, clinical outcome, HIV Infections, Virological response, Cohort Studies, Antiretroviral Therapy, Highly Active, Immunology and Allergy, Immunological response, Age Factor, HIV Infection, Child, Aged, 80 and over, immunological response, Clinical outcome, Medicine (all), Hazard ratio, Age Factors, Middle Aged, Viral Load, Europe, Infectious Diseases, Treatment Outcome, Child, Preschool, combination antiretroviral therapy, RNA, Viral, Survival Analysi, Viral load, Cohort study, Human, Combination antiretroviral therapy, Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, Immunology, virological response, Infectious Disease, Age, Age Distribution, Acquired immunodeficiency syndrome (AIDS), medicine, Humans, Survival analysis, Aged, business.industry, Infant, Newborn, Anti-HIV Agent, Infant, medicine.disease, HIV infection, Antiretroviral therapy, Survival Analysis, Confidence interval, CD4 Lymphocyte Count, age, Cohort Studie, business
Abstract: Objective: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. Design and setting: Multicohort collaboration of 33 European cohorts. Subjects: Forty-nine thousand nine hundred and twenty-one anti retroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006. Outcome measures: Time from combination antiretroviral therapy initiation to HIV RNA less than 50copies/ml (virological response), CD4 increase of more than 100cells/mu l (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. Results: The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. Conclusion: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Objective: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. Design and Setting: Multicohort collaboration of 33 European cohorts. Subjects: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006. Outcome Measures: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/Î¼l (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. Results: The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. Conclusion: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance. Â© 2008 Wolters Kluwer Health / Lippincott Williams & Wilkins.
Published: 2008

24. A whole-genome association study of major determinants for host control of HIV-1 RID A-6681-2009 RID A-2073-2010 RID B-5656-2009 RID F-2587-2010 RID G-8810-2011

Author: Fellay, J, Shianna, Kv, Ge, Dl, Colombo, S, Ledergerber, B, Weale, M, Zhang, Kl, Gumbs, C, Castagna, A, Cossarizza, A, Cozzi Lepri, A, DE LUCA, Andrea, Easterbrook, P, Francioli, P, Mallal, S, Martinez Picado, J, Miro, Jm, Obel, N, Smith, Jp, Wyniger, J, Descombes, P, Antonarakis, Se, Letvin, Nl, Mcmichael, Aj, Haynes, Bf, Telenti, A, and Goldstein, Db
Subjects: Male, Genome, HIV Infections, HLA-C Antigens, Single Nucleotide, Viral Load, DNA-Binding Proteins, Female, Genes, MHC Class I, Genome, Human, Haplotypes, HIV-1, HLA-B Antigens, Humans, Immediate-Early Proteins, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Regression Analysis, MHC Class I, Genes, Polymorphism, Human
Published: 2007

25. Causes of death among Danish HIV patients compared with population controls in the period 1995-2008.

Author: Helleberg, M., Kronborg, G., Larsen, C., Pedersen, G., Pedersen, C., Gerstoft, J., and Obel, N.
Subjects: HIV infection epidemiology, CONFIDENCE intervals, CAUSES of death, EPIDEMIOLOGICAL research, HIV-positive persons, MORTALITY, POISSON distribution, POPULATION research, VIRAL load, CASE-control method, DATA analysis software, DESCRIPTIVE statistics
Abstract: Purpose: To compare the mortality and causes of death in human immunodeficiency syndrome (HIV) patients with the background population. Methods: All adult HIV patients treated in Danish HIV centers from 1995 to 2008 and 14 controls for each HIV patient were included. Age-adjusted mortality rates (MR) and mortality rate ratios (MRR) were estimated using direct standardization and Poisson regression analyses. Up to four contributory causes of death for each person were included in analyses of cause-specific MR. Results: A total of 5,137 HIV patients and 71,918 controls were followed for 37,838 and 671,339 person-years (PY), respectively. Among non-injection drug use (IDU) HIV patients, the acquired immune deficiency syndrome (AIDS)-related MR/1,000 PY declined dramatically from 122.9 [95 % confidence interval (CI) 106.8-141.4] in 1995 to 5.0 (95 % CI 3.1-8.1) in 2008. The non-AIDS-related MR did not change substantially from 6.9 (95 % CI 3.8-12.5) to 5.6 (95 % CI 3.6-8.8). The MR of unnatural causes declined from 6.9 (95 % CI 3.8-12.5) to 2.7 (95 % CI 1.4-5.1). The MRR of infections declined from 46.6 (95 % CI 19.6-110.9) to 3.3 (95 % CI 1.6-6.6). The MRR of other natural causes of death remained constant. Conclusions: After the introduction of highly active antiretroviral therapy (HAART), the AIDS-related mortality has decreased substantially, but the long-term exposure to HIV and HAART has not translated into increasing mortality from malignancy, cardiovascular, and hepatic diseases. [ABSTRACT FROM AUTHOR]
Published: 2012
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26. Risk of high-level viraemia in HIV-infected patients on successful antiretroviral treatment for more than 6 months.

Author: Engsig, F. N., Omland, L. H., Larsen, M. V., Rasmussen, L. D., Qvist, T., Gerstoft, J., and Obel, N.
Subjects: VIREMIA, HIV-positive persons, ANTIRETROVIRAL agents, AIDS patients, INFECTIOUS disease transmission
Abstract: Objectives According to the Swiss Federal Commission for HIV/AIDS, HIV-infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic. Methods A Danish, population-based nationwide cohort study of HIV-infected patients with VL <51 HIV-1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time. Results We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients. Conclusion The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low. [ABSTRACT FROM AUTHOR]
Published: 2010
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27. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013:a collaborative analysis of cohort studies

Author: M. John Gill, Adam Trickey, Marta Montero, Leah Shepherd, Ard van Sighem, Sophie Grabar, Sophie Patterson, Timothy R. Sterling, Michael S. Saag, Charles Cazanave, Robert Zangerle, Christoph Boesecke, Niels Obel, Heidi M. Crane, Jonathan A C Sterne, Vicky Hernando, Jorg-Janne Vehreschild, Matthias Cavassini, Margaret T May, Amy C. Justice, Suzanne M Ingle, Fiona C Lampe, Antonella d'Arminio Monforte, Antiretroviral Therapy Cohort Collaboration, Trickey, A., May, M.T., Vehreschild, J.J., Obel, N., Gill, M.J., Crane, H.M., Boesecke, C., Patterson, S., Grabar, S., Cazanave, C., Cavassini, M., Shepherd, L., Monforte, A.D., van Sighem, A., Saag, M., Lampe, F., Hernando, V., Montero, M., Zangerle, R., Justice, A.C., Sterling, T., Ingle, S.M., and Sterne, JAC
Subjects: 0301 basic medicine, Epidemiology, business.industry, Immunology, Hazard ratio, Human immunodeficiency virus (HIV), medicine.disease_cause, medicine.disease, Comorbidity, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Virology, Health care, medicine, Life expectancy, 030212 general & internal medicine, business, Viral load, Demography, Cohort study
Abstract: BackgroundHealth care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.MethodsWe analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.Findings88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.InterpretationEven in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.FundingUK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.
Published: 2017

28. CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus\textendashInfected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC)

Author: Trickey, Adam, May, Margaret T, Schommers, Philipp, Tate, Jan, Ingle, Suzanne M, Guest, Jodie L, Gill, M John, Zangerle, Robert, Saag, Mike, Reiss, Peter, Monforte, Antonella, Johnson, Margaret, Lima, Viviane D, Sterling, Tim R, Cavassini, Matthias, Wittkop, Linda, Costagliola, Dominique, Sterne, Jonathan a C, Boulle, Andrew, Stephan, Christoph, Miró, José M, Chêne, Geneviève, Dabis, François, Monforte, Antonella d'Arminio, Amo, Julia, van Sighem, Ard, Vehreschild, Jorg Janne, Gill, John, Guest, Jodie, Haerry, David Hans-Ulrich, Hogg, Robert, Justice, Amy, Shepherd, Leah, Obel, Niels, Crane, Heidi M, Smith, Colette, Saag, Michael, Sterling, Tim, Teira, Ramon, Williams, Matthew, Sterne, Jonathan, May, Margaret, Ingle, Suzanne, University of Bristol [Bristol], University Hospital of Cologne [Cologne], Yale University [New Haven], Atlanta Veterans Affairs Medical Center [Decatur, GA, États-Unis], University of Calgary, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Alabama at Birmingham [ Birmingham] (UAB), University of Amsterdam [Amsterdam] (UvA), Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], Università degli Studi di Milano = University of Milan (UNIMI), Royal Free London NHS Foundation Trust, University of British Columbia (UBC), Vanderbilt University School of Medicine [Nashville], Lausanne University Hospital, Université de Lausanne = University of Lausanne (UNIL), Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Public Health and Family Medicine, University of Cape Town, Universitätsklinikum Frankfurt, CHU Bordeaux [Bordeaux], Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], VA Connecticut Healthcare System, Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Alabama [Tuscaloosa] (UA), AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Antiretroviral Therapy Cohort Collaboration (ART-CC), Boulle, A., Stephan, C., Miro, J.M., Cavassini, M., Chêne, G., Costagliola, D., Dabis, F., Monforte, A.D., Del Amo, J., Van Sighem, A., Vehreschild, J.J., Gill, J., Guest, J., Haerry, D.H., Hogg, R., Justice, A., Shepherd, L., Obel, N., Crane, H.M., Smith, C., Reiss, P., Saag, M., Sterling, T., Teira, R., Williams, M., Zangerle, R., Sterne, J., May, M., Ingle, S., and Trickey, A.
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, CD4:CD8 ratio, [SDV]Life Sciences [q-bio], CD4-CD8 Ratio, HIV Infections, CD8-Positive T-Lymphocytes, North America/epidemiology, CD8 ratio, CD8 count, HIV, antiretroviral therapy, mortality [CD4], 0302 clinical medicine, Cause of Death, 030212 general & internal medicine, Young adult, Articles and Commentaries, Cause of death, Hazard ratio, Middle Aged, Viral Load, Prognosis, 3. Good health, Europe, Infectious Diseases, Cohort, Female, Viral load, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, HIV Infections/drug therapy, Article, Europe/epidemiology, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Lymphocyte Count, Aged, Proportional Hazards Models, business.industry, Proportional hazards model, 030112 virology, mortality, Confidence interval, Anti-HIV Agents/therapeutic use, North America, business, Biomarkers, Biomarkers/blood
Abstract: Summary Associations of CD4:CD8 ratio or CD8 count with all-cause and cause-specific mortality were too small for them to be useful as independent prognostic markers in addition to CD4 count in virally suppressed patients on antiretroviral therapy with high CD4 count., Background We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. Methods We used data from 13 European and North American cohorts of human immunodeficiency virus–infected, antiretroviral therapy (ART)–naive adults who started ART during 1996–2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0–0.40, 0.41–0.64 [reference], >0.64) and CD8 count (0–760, 761–1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines. Results During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00–1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01–1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. Conclusions In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.
Published: 2017

29. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: A multinational, multicohort European study

Author: Wittkop, Linda, Arsandaux, Julie, Trevino, Ana, van der Loeff, Maarten Schim, Anderson, Jane, van Sighem, Ard, Böni, Jürg, Brun-Vezinet, Françoise, Soriano, Vicente, Boufassa, Faroudy, Brockmeyer, Norbert, Calmy, Alexandra, Dabis, François, Jarrin, Inma, Dorrucci, Maria, Duque, Vitor, Fätkenheuer, Gerd, Zangerle, Robert, Ferrer, Elena, Porter, Kholoud, Judd, Ali, Sipsas, Nikolaos V., Lambotte, Olivier, Shepherd, Leah, Leport, Catherine, Morrison, Charles, Mussini, Cristina, Obel, Niels, Ruelle, Jean, Schwarze-Zander, Carolyne, Sonnerborg, Anders, Teira, Ramon, Torti, Carlo, Valadas, Emilia, Colin, Celine, Friis-Møller, Nina, Costagliola, Dominique, Thiebaut, Rodolphe, Chene, Geneviève, Matheron, Sophie, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Krause, Murielle Mary, Ghosn, Jade, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Del Amo, Julia, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Mirò, Jose M., Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Sabin, Caroline, Garrido, Myriam, Haerry, David, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Amo, Julia del, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Leroy, Valériane, Lodi, Sara, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, van der Valk, Marc, Wyss, Natasha, Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM), Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Infectious Diseases, Hospital Carlos III, Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Homerton University Hospital, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Universität Zürich [Zürich] = University of Zurich (UZH), Université Paris Diderot - Paris 7 (UPD7), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Ruhr-Universität Bochum [Bochum], Geneva University Hospital (HUG), CHU de Bordeaux Pellegrin [Bordeaux], Instituto de Salud Carlos III [Madrid] (ISC), CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto Superiore di Sanità (ISS), Hospitais da Universidade de Coimbra (H.U.C.), University of Coimbra [Portugal] (UC), University Hospital of Cologne [Cologne], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Hospitalet de Llobregat, University College of London [London] (UCL), National and Kapodistrian University of Athens (NKUA), Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHI 360, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospital Bonn, Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Sierrallana Hospital, Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Universidade de Lisboa = University of Lisbon (ULISBOA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infectious diseases, Wittkop, L, Arsandaux, J, Trevino, A, van der Loeff, M, Anderson, J, van Sighem, A, Böni, J, Brun-Vezinet, F, Soriano, V, Boufassa, F, Brockmeyer, N, Calmy, A, Dabis, F, Jarrin, I, Dorrucci, M, Duque, V, Fätkenheuer, G, Zangerle, R, Ferrer, E, Porter, K, Judd, A, Sipsas, N, Lambotte, O, Shepherd, L, Leport, C, Morrison, C, Mussini, C, Obel, N, Ruelle, J, Schwarze-Zander, C, Sonnerborg, A, Teira, R, Torti, C, Valadas, E, Colin, C, Friis-Møller, N, Costagliola, D, Thiebaut, R, Chene, G, Matheron, S, Touloumi, G, Warszawski, J, Meyer, L, Krause, M, Ghosn, J, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Pérez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Monforte, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Mirò, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sönnerborg, A, Sabin, C, Garrido, M, Haerry, D, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Amo, J, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Leroy, V, Lodi, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, van der Valk, M, Wyss, N, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Superiore di Sanita [Rome], Gestionnaire, Hal Sorbonne Université, Wittkop, Linda, Arsandaux, Julie, Trevino, Ana, Van Der Loeff V Schim, Maarten, Anderson, Jane, Van Sighem, Ard, Jurg, Boni, Brun-Vezinet, Francoise, Soriano, Vicente, Boufassa, Faroudy, Brockmeyer, Norbert, Calmy, Alexandra, Dabis, Francoi, Jarrin, Inma, Dorrucci, Maria, Duque, Vitor, Fãtkenheuer, Gerd, Zangerle, Robert, Ferrer, Elena, Porter, Kholoud, Judd, Ali, Sipsas, Nikolaos V, Lambotte, Olivier, Shepherd, Leah, Leport, Catherine, Morrison, Charle, Mussini, Cristina, Obel, Niel, Ruelle, Jean, Schwarze-Zander, Carolyne, Sonnerborg, Ander, Teira, Ramon, Torti, Carlo, Valadas, Emilia, Colin, Celine, Friis-Moller, Nina, Costagliola, Dominique, Thiebaut, Rodolphe, Chene, Geneviève, Matheron, Sophie, on behalf of the COHERE in EuroCoord and ACHIeV2e Study, Group, and Castagna, Antonella
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, Internationality, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Gastroenterology, Anti-HIV Agents/administration & dosage/adverse effects/therapeutic use, Viral/blood, Cohort Studies, 0302 clinical medicine, CD4 HIV, Pharmacology (medical), 030212 general & internal medicine, Cd4 cell count, ddc:616, Confounding, virus diseases, Middle Aged, Viral Load, 3. Good health, [SDV] Life Sciences [q-bio], Europe, HIV-2/drug effects, Infectious Diseases, HIV-1/drug effects, RNA, Viral, Female, Viral load, Cohort study, Microbiology (medical), Cart, Adult, medicine.medical_specialty, Anti-HIV Agents, 030106 microbiology, 03 medical and health sciences, Internal medicine, medicine, Humans, Pharmacology, business.industry, CD4-Positive T-Lymphocytes/immunology/virology, CD4 Lymphocyte Count, Institutional repository, HIV Infections/blood/drug therapy/immunology/virology, HIV-2, HIV-1, RNA, Panton–Valentine leukocidin, business
Abstract: Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm(3) were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12months were + 105 (95% CI 77-134) in HIV-2+ patients and + 202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm(3) in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm(3)/year lower (95% CI 5-44; P=0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2
Published: 2017

30. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Author: Chereau, Fanny, Madec, Yoann, Sabin, Caroline, Obel, Niels, Ruiz-Mateos, Ezequiel, Chrysos, Georgios, Fidler, Sarah, Lehmann, Clara, Zangerle, Robert, Wittkop, Linda, Reiss, Peter, Hamouda, Osamah, Perez, Vicente Estrada, Leal, Manuel, Mocroft, Amanda, De Olalla, Patricia Garcia, Ammassari, Adriana, Monforte, Antonella D'Arminio, Mussini, Cristina, Segura, Ferran, Castagna, Antonella, Cavassini, Matthias, Grabar, Sophie, Morlat, Philippe, De Wit, Stéphane, Lambotte, Olivier, Meyer, Laurence, Judd, Ali, Touloumi, Giota, Warszawski, Josiane, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Del Amo, Julia, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Miró, Jose Ma, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M., Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Fanny, C, Yoann, M, Caroline, S, Niels, O, Ezequiel, R, Georgios, C, Sarah, F, Clara, L, Robert, Z, Linda, W, Peter, R, Osamah, H, Vicente Estrada, P, Manuel, L, Amanda, M, Patricia Garcia De, O, Adriana, A, Antonella D’Arminio, M, Cristina, M, Ferran, S, Antonella, C, Matthias, C, Sophie, G, Philippe, M, Stéphane De, W, Olivier, L, Laurence, M, Puoti, M, Chereau, F, Madec, Y, Sabin, C, Obel, N, Ruiz-Mateos, E, Chrysos, G, Fidler, S, Lehmann, C, Zangerle, R, Wittkop, L, Reiss, P, Hamouda, O, Perez, Ve, Leal, M, Mocroft, A, De Olalla, Pg, Ammassari, A, Monforte, Ada, Mussini, C, Segura, F, Castagna, A, Cavassini, M, Grabar, S, Morlat, P, De Wit, S, Lambotte, O, Meyer, L, The HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), HIV Monitoring Foundation, Augustinus Foundation, European Commission, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), University College London Hospitals (UCLH), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Hospital Universitario Virgen del Rocío [Sevilla], Tzaneio General Hospital, Imperial College London, German Center for Infection Research - Partner Site Bonn-Cologne (DZIF), Universität Innsbruck [Innsbruck], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Robert Koch Institute [Berlin] (RKI), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), University of Milan, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Hospital Universitari Parc Taulí of Sabadell, Barcelona, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Université de Lausanne (UNIL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université de Lausanne = University of Lausanne (UNIL), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, AII - Infectious diseases, APH - Aging & Later Life, Global Health, Amsterdam institute for Infection and Immunity, HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Research Council (MRC)
Subjects: Male, HIV Infections, CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Immunodeficiency Viruses, HIV-1/immunology, Public and Occupational Health, lcsh:Science, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV-1, Humans, Viral Load, Viremia, Virus Replication, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), virus diseases, CD8-Positive T-Lymphocytes/drug effects, Antiretroviral Therapy, Highly Active/methods, Medical Microbiology, Viral Pathogens, Science & Technology - Other Topics, Human, Blood cells, Immunology, HIV Infections/drug therapy, Virus Replication/immunology, Men WHO Have Sex with Men, Cytotoxic T cells, Microbiology, Viremia/drug therapy, Microbial Pathogens, Science & Technology, lcsh:R, Organisms, Biology and Life Sciences, Anti-HIV Agent, NATURAL-HISTORY, CD8-Positive T-Lymphocyte, Anti-HIV Agents/therapeutic use, HIV CD4 AIDS, T-CELLS, Population Groupings, lcsh:Q, Preventive Medicine, Sexuality Groupings, RNA viruses, RNA LEVELS, lcsh:Medicine, PROGRESSION, ACTIVATION, INFECTION, Cellular types, Medicine and Health Sciences, HIV Infection, Medicine (all), Immune cells, HIV diagnosis and management, ABSENCE, Vaccination and Immunization, Multidisciplinary Sciences, Infectious Diseases, CD4-Positive T-Lymphocyte, Viruses, White blood cells, Pathogens, Research Article, Cell biology, Evolutionary Immunology, Infectious Disease Control, General Science & Technology, T cells, Antiretroviral Therapy, CD4-Positive T-Lymphocytes/drug effects, CD4 Lymphocyte Count/methods, Viral Evolution, Antiviral Therapy, Virology, MD Multidisciplinary, Retroviruses, Evolutionary Biology, Lentivirus, HIV, Viral Load/drug effects, Diagnostic medicine, Organismal Evolution, Animal cells, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, REPLICATION, People and Places, Microbial Evolution, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, CD8-Positive T-Lymphocytes/immunology, HIV Infections/immunology, HIV Infections/virology, Viral Load/immunology, Viremia/immunology, Viremia/virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, INVERSE PROBABILITY
Abstract: [Objective] HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control., [Methods] HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models., [Results] We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds., [Discussion] Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs., The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694.
Published: 2017

31. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Author: Andrea De Luca, Aaron J. Deutsch, Deepti Gurdasani, David W. Haas, Jean-François Zagury, Susan Buchbinder, Simon Mallal, Manjinder S. Sandhu, Steven M. Wolinsky, Cédric Coulonges, Laurence Meyer, Paul I.W. de Bakker, James I. Mullins, Daniëlle van Manen, Andrea Cossarizza, José M. Miró, Amy C. Weintrob, Tobias L. Lenz, Judith Dalmau, Olivier Lambotte, Niels Obel, James J. Goedert, Mary Carrington, Ma Luo, Arman Bashirova, David Goldstein, Gregory D. Kirk, Joshua T. Herbeck, Amalio Telenti, Paul J. McLaren, Patrick R. Shea, Javier Martinez-Picado, Cheryl A. Winkler, Bruce D. Walker, Istvan Bartha, Jacques Fellay, Ioannis Theodorou, Hanneke Schuitemaker, Guido Poli, Eric O. Johnson, Soumya Raychaudhuri, Other departments, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, Mclaren, Pj, Coulonges, C, Bartha, I, Lenz, Tl, Deutsch, Aj, Bashirova, A, Buchbinder, S, Carrington, Mn, Cossarizza, A, Dalmau, J, De Luca, A, Goedert, Jj, Gurdasani, D, Haas, Dw, Herbeck, Jt, Johnson, Eo, Kirk, Gd, Lambotte, O, Luo, M, Mallal, S, van Manen, D, Martinez Picado, J, Meyer, L, Miro, Jm, Mullins, Ji, Obel, N, Poli, Guido, Sandhu, M, Schuitemaker, H, Shea, Pr, Theodorou, I, Walker, Bd, Weintrob, Ac, Winkler, Ca, Wolinsky, Sm, Raychaudhuri, S, Goldstein, Db, Telenti, A, de Bakker, Pi, Zagury, Jf, and Fellay, J.
Subjects: Adult, Receptors, CCR5, infectious disease, Inheritance Patterns, Genome-wide association study, Peptide binding, Human leukocyte antigen, Biology, heritability, Research Support, Settore MED/17 - MALATTIE INFETTIVE, Polymorphism, Single Nucleotide, Genomics, GWAS, Heritability, HIV-1 control, Infectious disease, Journal Article, genomics, Humans, Genetic Predisposition to Disease, Allele, Amino Acids, Non-U.S. Gov't, Genotyping, Alleles, Genetic association, Genetics, Multidisciplinary, Research Support, Non-U.S. Gov't, Haplotype, Viral Load, Biological Sciences, Physical Chromosome Mapping, HLA-B Antigens, Host-Pathogen Interactions, HIV-1, Chromosomes, Human, Pair 3, Viral load, Genome-Wide Association Study
Abstract: Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between similar to 8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5 Delta 32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.
Published: 2015

32. Copy Number Variation of KIR Genes Influences HIV-1 Control

Author: Barton F. Haynes, Kevin V. Shianna, Galit Alter, Jeremy J. Martinson, Andrew J. McMichael, David Goldstein, Persephone Borrow, Steven M. Wolinsky, Anna C. Need, Aids Vaccine Immunology, Norman L. Letvin, Kimberly Pelak, Jay H. Bream, Dongliang Ge, Andrea De Luca, Maureen P. Martin, Javier Martinez-Picado, Thomas J. Urban, Jacques Fellay, Sheng Feng, Amalio Telenti, Beth D. Jamieson, Mary Carrington, NIAID Center for HIV/AIDS Vaccine Immunology, Haynes, B., Goldstein, D., Telenti, A., Ledergerber, B., Francioli, P., d'Arminio Monforte, A., De Luca, A., Castagna, A., Mallal, S., Martinez-Picado, J., Dalmau, J., Easterbrook, P., Obel, N., Cossarizza, A., Gatell, JM., Margolick, J., Phair, J., Detels, R., Rinaldo, C., Jacobson, L., Pelak, Kimberly, Need, Anna C., Fellay, Jacque, Shianna, Kevin V., Feng, Sheng, Urban, Thomas J., Ge, Dongliang, De Luca, Andrea, Martinez picado, Javier, Wolinsky, Steven M., Martinson, Jeremy J., Jamieson, Beth D., Bream, Jay H., Martin, Maureen P., Borrow, Persephone, Letvin, Norman L., Mcmichael, Andrew J., Haynes, Barton F., Telenti, Amalio, Carrington, Mary, Goldstein, David B., Alter, Galit, and Castagna, Antonella
Subjects: Immunology and Microbiology (all), Cell, Ly49 Receptor Repertoire, Kir3Ds1, Lymphocyte Activation, Virus Replication, Virus Type-1 Infection, Cohort Studies, 0302 clinical medicine, Receptors, KIR, Models, Gene Duplication, Receptors, Genetics of the Immune System, Killer Cells, Copy-number variation, Biology (General), Receptor, DNA Copy Number Variation, Genetics, 0303 health sciences, General Neuroscience, Viral Load, 3. Good health, KIR, Killer Cells, Natural, medicine.anatomical_structure, Immunological, Nk Cells, Natural, Disease Progression, DNA Copy Number Variations, HIV-1/immunology, HIV-1/physiology, Humans, Killer Cells, Natural/metabolism, Killer Cells, Natural/physiology, Models, Immunological, Receptors, KIR/genetics, Receptors, KIR/metabolism, Inhibitory Receptors, General Agricultural and Biological Sciences, KIR3DL1, Viral load, Natural-Killer-Cells, Research Article, Human, HIV-1, QH301-705.5, Immunology, chemical and pharmacologic phenomena, Biology, Settore MED/17 - MALATTIE INFETTIVE, General Biochemistry, Genetics and Molecular Biology, Molecular Genetics, 03 medical and health sciences, MHC class I, medicine, otorhinolaryngologic diseases, Genome-Wide Association Studies, Gene, 030304 developmental biology, Mhc Class-I, Neuroscience (all), Biochemistry, Genetics and Molecular Biology (all), General Immunology and Microbiology, Human Genetics, Molecular biology, Viral replication, Agricultural and Biological Sciences (all), biology.protein, Hla Class-I, Cutting Edge, Cohort Studie, 030215 immunology
Abstract: The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control., A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection., Author Summary There is marked intrinsic variation in the extent to which individuals are able to control HIV-1. We have identified a genetic copy number variable region (CNV) in humans that plays a significant role in the control of HIV-1. This CNV is located in the genomic region that encodes the killer cell immunoglobulin-like receptors (KIRs) and specifically affects the KIR3DS1 and KIR3DL1 genes, encoding two KIRs that interact with human leukocyte antigen B (HLA-B) ligands. KIRs are expressed on the surface of natural killer (NK) cells, which serve as important players in the innate immune response, and are involved in the recognition of infected and malignant cells through a loss or alteration in “self” ligands. We use both genetic association and functional evidence to show a strong interaction between KIR3DL1 and KIR3DS1, indicating that increasing gene counts for KIR3DL1 confer increasing levels of protection against HIV-1, but only in the presence of at least one copy of KIR3DS1. This effect was associated with a dramatic increase in the abundance of KIR3DS1+ NK cells in the peripheral blood, and strongly associated with a more robust capacity of peripheral NK cells to suppress HIV-1 replication in vitro. This work provides one of the few examples of an association between a relatively common CNV and a human complex trait.

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32 results on '"Obel, N"'

1. Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

2. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.

3. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

4. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients.

5. No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010.

6. Poor CD4 response despite viral suppression is associated with increased non-AIDS-related mortality among HIV patients and their parents.

7. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

8. Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study.

9. Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years.

10. The insufficient suppression of viral load by saquinavir hard gel is reversible: a retrospective cohort study.

11. The Incidence of AIDS-Defining Illnesses at a Current CD4 Count ≥200 Cells/μL in the Post—Combination Antiretroviral Therapy Era

12. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

13. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

14. CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies

15. Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

16. Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

17. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients

18. Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

19. Predictors of CD4(+) T-cell counts of HIV type 1-infected persons after virologic failure of all 3 original antiretroviral drug classes

20. The incidence of AIDS-defining illnesses at a current CD4 count ≥200 cells/μL in the post-combination antiretroviral therapy era

21. Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study

22. Risk of virus transmission from well-treated patients with HIV?

23. Response to combination antiretroviral therapy: Variation by age

24. A whole-genome association study of major determinants for host control of HIV-1 RID A-6681-2009 RID A-2073-2010 RID B-5656-2009 RID F-2587-2010 RID G-8810-2011

25. Causes of death among Danish HIV patients compared with population controls in the period 1995-2008.

26. Risk of high-level viraemia in HIV-infected patients on successful antiretroviral treatment for more than 6 months.

27. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013:a collaborative analysis of cohort studies

28. CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus\textendashInfected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC)

29. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: A multinational, multicohort European study

30. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

31. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

32. Copy Number Variation of KIR Genes Influences HIV-1 Control

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