30 results on '"Schomaker, Michael"'
Search Results
2. High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.
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Nyakato P, Christ B, Anderegg N, Muhairwe J, Jefferys L, van Dijk J, Vinikoor MJ, van Lettow M, Chimbetete C, Phiri SJ, Egger M, Ballif M, Yiannoutsos CT, Schomaker M, Kassanjee R, Davies MA, and Cornell M
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- Child, Infant, Young Adult, Humans, Adolescent, Anti-Retroviral Agents therapeutic use, Africa, Southern epidemiology, Proportional Hazards Models, Lost to Follow-Up, HIV Infections drug therapy, Anti-HIV Agents therapeutic use
- Abstract
Background: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost., Methods: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer., Results: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]., Conclusions: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2022
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3. The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy.
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Kerschberger B, Boulle A, Kuwengwa R, Ciglenecki I, and Schomaker M
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- Adolescent, Adult, Antitubercular Agents therapeutic use, Eswatini, Female, Humans, Male, Middle Aged, Patient Dropouts, Policy, Public Sector, Retrospective Studies, Survival Analysis, Time-to-Treatment, Tuberculosis drug therapy, World Health Organization, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections epidemiology, Tuberculosis epidemiology
- Abstract
Rapid initiation of antiretroviral therapy (ART) is recommended for people living with human immunodeficiency virus (HIV), with the option to start treatment on the day of diagnosis (same-day ART). However, the effect of same-day ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under a treat-all policy in Nhlangano (Eswatini) during 2014-2016, either on the day of HIV care enrollment (same-day ART) or 1-14 days thereafter (early ART). Directed acyclic graphs, flexible parametric survival analysis, and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on a composite unfavorable treatment outcome (loss to follow-up, death, viral failure, treatment switch). Of 1,328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavorable outcome was higher, 1.48 (95% confidence interval: 1.16, 1.89), for same-day ART compared with early ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavorable outcome under same-day ART compared with 21.2% under early ART (difference: 7.7%; 1.3%-14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrollment and a similar hazard thereafter. We found an increased risk with same-day ART. A limitation was that possible silent transfers that were not captured., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)
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- 2021
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4. Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.
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Nyakato P, Schomaker M, Sipambo N, Technau KG, Fatti G, Rabie H, Tanser F, Eley B, Euvrard J, Wood R, Tsondai PR, Yiannoutsos CT, Cornell M, and Davies MA
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- Adolescent, Adult, Africa, Southern, Child, Female, Humans, Male, Retrospective Studies, South Africa epidemiology, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
- Abstract
Background and Objectives: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with non-perinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence., Design: A retrospective cohort study., Methods: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004-2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs., Results: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex., Conclusions: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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5. Increased Mortality With Delayed and Missed Switch to Second-Line Antiretroviral Therapy in South Africa.
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Bell Gorrod H, Court R, Schomaker M, Maartens G, and Murphy RA
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- Adult, CD4 Lymphocyte Count, Cohort Studies, Humans, Middle Aged, South Africa epidemiology, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections mortality
- Abstract
Background: After failure of first-line antiretroviral therapy (ART) in the public sector, delayed or missed second-line ART switch is linked with poor outcomes in patients with advanced HIV., Setting: We investigated delayed or missed second-line ART switch after confirmed virologic failure in the largest private sector HIV cohort in Africa., Methods: We included HIV-infected adults with confirmed virologic failure after 6 months of nonnucleoside reverse-transcriptase inhibitor-based ART. We estimated the effect of timing of switch on the hazard of death using inverse probability of treatment weighting of marginal structural models. We adjusted for time-dependent confounding of CD4 count, viral load, and visit frequency., Results: Five thousand seven hundred forty-eight patients (53% female) with confirmed virologic failure met inclusion criteria; the median age was 40 [interquartile range (IQR): 35-47], advanced HIV was present in 48% and the prior duration of nonnucleoside reverse-transcriptase inhibitor-based ART was 1083 days (IQR: 665-1770). Median time to confirmation of virologic failure and to second-line switch was 196 (IQR: 136-316) and 220 days (IQR: 65-542), respectively. Switching to second-line ART after confirmed failure compared with remaining on first-line ART reduced risk of subsequent death [adjusted hazard ratio: 0.47 (95% confidence interval: 0.36 to 0.63)]. Compared with patients who experienced delayed switch, those switched immediately had a lower risk of death, regardless of CD4 cell count., Conclusions: Delayed or missed switch to second-line ART after confirmed first-line ART failure is common in the South African private sector and associated with mortality. Novel interventions to minimize switch delay should be tested and not limited to those with advanced disease at treatment failure.
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- 2020
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6. PS-SiZer map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration.
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Harezlak J, Sarwat S, Wools-Kaloustian K, Schomaker M, Balestre E, Law M, Kiertiburanakul S, Fox M, Huis In 't Veld D, Musick BS, and Yiannoutsos CT
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- Adult, Africa, Africa, Southern, Anti-HIV Agents therapeutic use, Biomarkers blood, Computer Simulation, Data Interpretation, Statistical, Female, Humans, Longitudinal Studies, Male, Anti-HIV Agents pharmacology, Body Weight drug effects, HIV Infections drug therapy, HIV Infections physiopathology, Weight Gain
- Abstract
Objectives: We extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy., Methods: We propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain., Results: Through simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens., Discussion: PS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves., Competing Interests: The authors have declared that no competing interests exist.
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- 2020
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7. HIV programmatic outcomes following implementation of the 'Treat-All' policy in a public sector setting in Eswatini: a prospective cohort study.
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Kerschberger B, Schomaker M, Jobanputra K, Kabore SM, Teck R, Mabhena E, Mthethwa-Hleza S, Rusch B, Ciglenecki I, and Boulle A
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- Adolescent, Adult, Anti-HIV Agents administration & dosage, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Eligibility Determination, Eswatini, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pregnancy, Proportional Hazards Models, Prospective Studies, Public Sector, Standard of Care, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
- Abstract
Introduction: The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini., Methods: This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm
3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure., Results: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine., Conclusions: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)- Published
- 2020
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8. Feasibility of antiretroviral therapy initiation under the treat-all policy under routine conditions: a prospective cohort study from Eswatini.
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Kerschberger B, Jobanputra K, Schomaker M, Kabore SM, Teck R, Mabhena E, Lukhele N, Rusch B, Boulle A, and Ciglenecki I
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- Adult, Anti-HIV Agents administration & dosage, CD4 Lymphocyte Count, Eligibility Determination, Eswatini, Feasibility Studies, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pregnancy, Proportional Hazards Models, Prospective Studies, Time-to-Treatment, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
- Abstract
Introduction: The World Health Organization recommends the Treat-All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource-poor settings. We assessed the feasibility of Treat-All compared with standard of care (SOC) under routine conditions., Methods: This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat-All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm
3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan-Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions., Results: Of the 1726 (57.3%) patients enrolled under Treat-All and 1287 (42.7%) under SOC, cumulative three-month ART initiation was higher under Treat-All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat-All, ART initiation was higher in pregnant women (vs. non-pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV-positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3-month ART initiation was similar in both interventions (91% to 92%) although Treat-All initiated patients more quickly during the first month after HIV care enrolment., Conclusions: ART initiation was high under Treat-All and without evidence of de-prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long-term impact of Treat-All on patient outcomes., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)- Published
- 2019
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9. Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.
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Kerschberger B, Schomaker M, Ciglenecki I, Pasipamire L, Mabhena E, Telnov A, Rusch B, Lukhele N, Teck R, and Boulle A
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- Adult, Anti-HIV Agents administration & dosage, CD4 Lymphocyte Count, Eligibility Determination, Eswatini, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Pregnancy, Program Evaluation, Proportional Hazards Models, Public Sector statistics & numerical data, Retrospective Studies, Rural Population, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Medication Adherence statistics & numerical data, Time-to-Treatment statistics & numerical data
- Abstract
Objectives: To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland)., Methods: This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates., Results: Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm
3 ). The active treatment cohort expanded 8.4-fold, ART coverage increased 8.0-fold (7.1% in 2006 vs. 56.8% in 2014) and 12-month crude ART retention improved from 71% to 86%. Compared with the pre-decentralisation period (2006-2007), attrition decreased by 5% (adjusted hazard ratio [aHR] 0.95, 95% confidence interval 0.88-1.02) during HIV-TB service decentralisation (2008-2010), by 17% (aHR 0.83, 0.75-0.92) during service consolidation (2011-2012), and by 20% (aHR 0.80, 0.71-0.90) during further treatment expansion (2013-2014). The risk of attrition was higher for young age, male sex, pathological baseline haemoglobin and biochemistry results, more toxic drug regimens, WHO III/IV staging and low CD4 cell count; access to a telephone was protective., Conclusions: Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)- Published
- 2019
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10. Twelve-year mortality in adults initiating antiretroviral therapy in South Africa.
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Cornell M, Johnson LF, Wood R, Tanser F, Fox MP, Prozesky H, Schomaker M, Egger M, Davies MA, and Boulle A
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- Adolescent, Adult, Aged, Aged, 80 and over, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections epidemiology, HIV Infections immunology, Humans, Male, Middle Aged, South Africa epidemiology, Survival Analysis, Viral Load, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections mortality
- Abstract
Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa., Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004-2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of follow-up was the secondary outcome., Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02-3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007-2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIV-negative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4 strata. Three-quarters of patients had VLs in their last year, and 86% of these were virally suppressed., Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale-up, testing and initiating men on ART must be a national priority.
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- 2017
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11. Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children Ages 1-5 Years: A Causal Modeling Analysis.
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Schomaker M, Davies MA, Malateste K, Renner L, Sawry S, N'Gbeche S, Technau KG, Eboua F, Tanser F, Sygnaté-Sy H, Phiri S, Amorissani-Folquet M, Cox V, Koueta F, Chimbete C, Lawson-Evi A, Giddy J, Amani-Bosse C, Wood R, Egger M, and Leroy V
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- Burkina Faso, CD4 Lymphocyte Count, Causality, Child, Preschool, Cohort Studies, Cote d'Ivoire, Databases, Factual, Female, Ghana, HIV Infections immunology, HIV Infections mortality, Humans, Infant, Malawi, Male, Senegal, South Africa, Time Factors, Togo, Zimbabwe, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, Child Development, Early Medical Intervention, HIV Infections drug therapy
- Abstract
Background: There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions., Methods: ART-naïve children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation., Results: About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count <750 cells/mm³ or CD4% <25% was 0.2% (95% CI = -0.2%; 0.3%), and the difference in the mean height-for-age z-scores of those who survived was -0.02 (95% CI = -0.04; 0.01). Younger children ages 1-2 and children in West Africa had worse outcomes., Conclusions: Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, although we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below 750/25%.
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- 2016
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12. A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment.
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Johnson LF, Dorrington RE, Laubscher R, Hoffmann CJ, Wood R, Fox MP, Cornell M, Schomaker M, Prozesky H, Tanser F, Davies MA, and Boulle A
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- Adolescent, Adult, Child, Child, Preschool, Female, HIV Infections drug therapy, Humans, Infant, Male, South Africa epidemiology, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections mortality, Registries
- Abstract
Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART)., Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes., Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults)., Conclusions: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.
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- 2015
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13. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.
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Kerschberger B, Boulle AM, Kranzer K, Hilderbrand K, Schomaker M, Coetzee D, Goemaere E, and Van Cutsem G
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- Adult, Ambulatory Care Facilities, Female, Health Resources, Humans, Male, Middle Aged, Retrospective Studies, South Africa, Time Factors, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Viral Load drug effects
- Abstract
Introduction: Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART., Methods: This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models., Results: In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001)., Conclusions: A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.
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- 2015
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14. Simultaneous Treatment of Missing Data and Measurement Error in HIV Research Using Multiple Overimputation.
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Schomaker M, Hogger S, Johnson LF, Hoffmann CJ, Bärnighausen T, and Heumann C
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- CD4 Lymphocyte Count, Computer Simulation, HIV Infections immunology, HIV Infections mortality, HIV Infections virology, Humans, Proportional Hazards Models, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, Bias, Data Interpretation, Statistical, HIV Infections drug therapy, Models, Statistical, Survival Analysis
- Abstract
Background: Both CD4 count and viral load in HIV-infected persons are measured with error. There is no clear guidance on how to deal with this measurement error in the presence of missing data., Methods: We used multiple overimputation, a method recently developed in the political sciences, to account for both measurement error and missing data in CD4 count and viral load measurements from four South African cohorts of a Southern African HIV cohort collaboration. Our knowledge about the measurement error of ln CD4 and log10 viral load is part of an imputation model that imputes both missing and mismeasured data. In an illustrative example, we estimate the association of CD4 count and viral load with the hazard of death among patients on highly active antiretroviral therapy by means of a Cox model. Simulation studies evaluate the extent to which multiple overimputation is able to reduce bias in survival analyses., Results: Multiple overimputation emphasizes more strongly the influence of having high baseline CD4 counts compared to both a complete case analysis and multiple imputation (hazard ratio for >200 cells/mm vs. <25 cells/mm: 0.21 [95% confidence interval: 0.18, 0.24] vs. 0.38 [0.29, 0.48], and 0.29 [0.25, 0.34], respectively). Similar results are obtained when varying assumptions about measurement error, when using p-splines, and when evaluating time-updated CD4 count in a longitudinal analysis. The estimates of the association with viral load are slightly more attenuated when using multiple imputation instead of multiple overimputation. Our simulation studies suggest that multiple overimputation is able to reduce bias and mean squared error in survival analyses., Conclusions: Multiple overimputation, which can be used with existing software, offers a convenient approach to account for both missing and mismeasured data in HIV research.
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- 2015
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15. Age in antiretroviral therapy programmes in South Africa: a retrospective, multicentre, observational cohort study.
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Cornell M, Johnson LF, Schomaker M, Tanser F, Maskew M, Wood R, Prozesky H, Giddy J, Stinson K, Egger M, Boulle A, and Myer L
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- Adult, Age Factors, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, Follow-Up Studies, HIV Infections mortality, Humans, Male, Needs Assessment organization & administration, Retrospective Studies, Risk Factors, South Africa epidemiology, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Program Development, Public Health
- Abstract
Background: As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status., Methods: In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age., Findings: Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older., Interpretation: Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV., Funding: National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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16. Do increasing rates of loss to follow-up in antiretroviral treatment programs imply deteriorating patient retention?
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Johnson LF, Estill J, Keiser O, Cornell M, Moolla H, Schomaker M, Grimsrud A, Davies MA, and Boulle A
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- Bias, Computer Simulation, HIV Infections mortality, Humans, Medication Adherence, Research Design, Survival Analysis, Time Factors, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Lost to Follow-Up
- Abstract
In several studies of antiretroviral treatment (ART) programs for persons with human immunodeficiency virus infection, investigators have reported that there has been a higher rate of loss to follow-up (LTFU) among patients initiating ART in recent years than among patients who initiated ART during earlier time periods. This finding is frequently interpreted as reflecting deterioration of patient retention in the face of increasing patient loads. However, in this paper we demonstrate by simulation that transient gaps in follow-up could lead to bias when standard survival analysis techniques are applied. We created a simulated cohort of patients with different dates of ART initiation. Rates of ART interruption, ART resumption, and mortality were assumed to remain constant over time, but when we applied a standard definition of LTFU, the simulated probability of being classified LTFU at a particular ART duration was substantially higher in recently enrolled cohorts. This suggests that much of the apparent trend towards increased LTFU may be attributed to bias caused by transient interruptions in care. Alternative statistical techniques need to be used when analyzing predictors of LTFU--for example, using "prospective" definitions of LTFU in place of "retrospective" definitions. Similar considerations may apply when analyzing predictors of LTFU from treatment programs for other chronic diseases., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2014
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17. Virologic response in children treated with abacavir-compared with stavudine-based antiretroviral treatment: a South African multi-cohort analysis.
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Technau KG, Schomaker M, Kuhn L, Moultrie H, Coovadia A, Eley B, Rabie H, Wood R, Cox V, Vizcaya LS, Muchiri E, and Davies MA
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- Adolescent, Child, Cohort Studies, Female, HIV Infections epidemiology, HIV Infections virology, Humans, Male, South Africa epidemiology, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, Dideoxynucleosides therapeutic use, HIV isolation & purification, HIV Infections drug therapy, Stavudine therapeutic use
- Abstract
Background: Initiation criteria and pediatric antiretroviral treatment regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use of abacavir (ABC)-based regimens at 1 large site: here, we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration., Methods: Data for 9543 antiretroviral treatment-naïve children <16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at 6 clinics in Johannesburg and Cape Town, South Africa, were analyzed with χ tests and logistic regression to evaluate viral suppression at 6 and 12 months., Results: Prevalence of viral suppression at 6 months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, P < 0.0001). Among 3189 children started on a d4T-based EFV regimen, a higher proportion (86%) achieved suppression at 6 months compared with 391 children started on ABC-containing EFV regimens (78%, P < 0.0001). Relative benefit of d4T versus ABC on 6-month suppression remained in multivariate analysis after adjustment for pretreatment characteristics, cohort and year of program [LPV/r: odds ratio = 0.57 (confidence interval: 0.46-0.72); EFV: odds ratio = 0.46 (confidence interval: 0.32-0.65)]., Conclusions: This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line antiretroviral treatment in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long-term outcomes.
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- 2014
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18. Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen.
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Moholisa RR, Schomaker M, Kuhn L, Meredith S, Wiesner L, Coovadia A, Strehlau R, Martens L, Abrams EJ, Maartens G, and McIlleron H
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- Antiretroviral Therapy, Highly Active, Child, Preschool, Drug Monitoring, Female, Humans, Infant, Male, Retrospective Studies, Treatment Failure, Treatment Outcome, Viral Load, Viremia, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors therapeutic use, HIV-1
- Abstract
Background: Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml., Methods: A total of 237 HIV-infected children aged 4-42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml., Results: The median (IQR) pretreatment CD4(+) T-lymphocyte percentage was 18.80% (12.70-25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were -2.17 (-3.35--2.84) and -3.34 (-4.57--3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11-12.42) at median (IQR) 3.50 h (2.67-4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores., Conclusions: Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail.
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- 2014
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19. When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa.
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Schomaker M, Egger M, Ndirangu J, Phiri S, Moultrie H, Technau K, Cox V, Giddy J, Chimbetete C, Wood R, Gsponer T, Bolton Moore C, Rabie H, Eley B, Muhe L, Penazzato M, Essajee S, Keiser O, and Davies MA
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- Africa, Southern, Anti-HIV Agents therapeutic use, Child, Preschool, Cohort Studies, Cooperative Behavior, Disease Progression, Drug Administration Schedule, Humans, Models, Biological, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, HIV Infections drug therapy
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Background: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%., Methods and Findings: ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data., Conclusions: The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.
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- 2013
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20. Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
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McIlleron HM, Schomaker M, Ren Y, Sinxadi P, Nuttall JJ, Gous H, Moultrie H, Eley B, Merry C, Smith P, Haas DW, and Maartens G
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- Alkynes, Anti-HIV Agents administration & dosage, Benzoxazines administration & dosage, Child, Child, Preschool, Cyclopropanes, Cytochrome P-450 CYP2B6, Drug Interactions, Female, Genotype, HIV Infections complications, Humans, Male, Plasma chemistry, Tuberculosis complications, Anti-HIV Agents pharmacokinetics, Antitubercular Agents therapeutic use, Aryl Hydrocarbon Hydroxylases genetics, Benzoxazines pharmacokinetics, HIV Infections drug therapy, Rifampin therapeutic use, Tuberculosis drug therapy
- Abstract
Objectives: An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis., Design: Plasma efavirenz concentrations were compared in 40 children during concomitant treatment for tuberculosis and HIV-1, after stopping rifampicin, and in a control group of children without tuberculosis. Associations with antituberculosis treatment, metabolizer genotype (based on CYP2B6 516G→T, 983T→C, and 15582C→T), weight, and time after dose were evaluated., Results: Compared to children with extensive metabolizer genotypes, efavirenz concentrations were increased 1.42-fold (95% confidence interval, CI 0.94–2.15) and 2.85-fold (95% CI 1.80–4.52) in children with intermediate and slow metabolizer genotypes, respectively. Concomitant antituberculosis treatment increased efavirenz concentrations 1.49-fold (95% CI 1.10–2.01) in children with slow metabolizer genotypes, but did not affect efavirenz concentrations in extensive or intermediate metabolizer genotypes. After adjustment for dose/kg, each kilogram of weight was associated with a 2.8% (95% CI 0.9–4.7) decrease in efavirenz concentrations. Despite higher milligram per kilogram doses, a higher proportion of children in the lowest weight band (10–13.9 kg) had efavirenz concentrations less than 1.0 mg/l than larger children., Conclusion: Antituberculosis treatment was not associated with reduced efavirenz concentrations in children, which does not support increased efavirenz doses. Children with slow metabolizer genotype have increased efavirenz concentrations during antituberculosis treatment, likely due to isoniazid inhibiting enzymes involved in accessory metabolic pathways for efavirenz.
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- 2013
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21. CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa.
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Hoffmann CJ, Schomaker M, Fox MP, Mutevedzi P, Giddy J, Prozesky H, Wood R, Garone DB, Egger M, and Boulle A
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- Adolescent, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections drug therapy, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, RNA, Viral blood, South Africa epidemiology, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections immunology, HIV Infections mortality
- Abstract
Background: In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information., Methods: We analyzed data from a large multicohort study in South Africa, where HIV RNA is routinely monitored. Adult HIV-positive patients initiating cART between 2003 and 2010 were included. Mortality was analyzed in Cox models; CD4 count slope by HIV RNA level was assessed using linear mixed models., Results: About 44,829 patients (median age: 35 years, 58% female, median CD4 count at cART initiation: 116 cells/mm) were followed up for a median of 1.9 years, with 3706 deaths. Mean CD4 count slopes per week ranged from 1.4 [95% confidence interval (CI): 1.2 to 1.6] cells per cubic millimeter when HIV RNA was <400 copies per milliliter to -0.32 (95% CI: -0.47 to -0.18) cells per cubic millimeter with >100,000 copies per milliliter. The association of CD4 slope with mortality depended on current CD4 count: the adjusted hazard ratio (aHRs) comparing a >25% increase over 6 months with a >25% decrease was 0.68 (95% CI: 0.58 to 0.79) at <100 cells per cubic millimeter but 1.11 (95% CI: 0.78 to 1.58) at 201-350 cells per cubic millimeter. In contrast, the aHR for current CD4 count, comparing >350 with <100 cells per cubic millimeter, was 0.10 (95% CI: 0.05 to 0.20)., Conclusions: Absolute CD4 count remains a strong risk for mortality with a stable effect size over the first 4 years of cART. However, CD4 count slope and HIV RNA provide independently added to the model.
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- 2013
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22. Immune recovery after starting ART in HIV-infected patients presenting and not presenting with tuberculosis in South Africa.
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Schomaker M, Egger M, Maskew M, Garone D, Prozesky H, Hoffmann CJ, Boulle A, and Fenner L
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- AIDS-Related Opportunistic Infections drug therapy, AIDS-Related Opportunistic Infections immunology, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, HIV Infections drug therapy, Humans, Male, South Africa, Tuberculosis drug therapy, Tuberculosis immunology, Viral Load, AIDS-Related Opportunistic Infections complications, Anti-HIV Agents therapeutic use, HIV Infections complications, HIV Infections immunology, Tuberculosis complications
- Abstract
We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.
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- 2013
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23. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies.
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Johnson LF, Mossong J, Dorrington RE, Schomaker M, Hoffmann CJ, Keiser O, Fox MP, Wood R, Prozesky H, Giddy J, Garone DB, Cornell M, Egger M, and Boulle A
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- Adult, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections drug therapy, HIV Seropositivity, Humans, Male, Middle Aged, Sex Factors, South Africa epidemiology, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections mortality, Life Expectancy
- Abstract
Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults., Methods and Findings: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations., Conclusions: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.
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- 2013
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24. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.
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Cornell M, Schomaker M, Garone DB, Giddy J, Hoffmann CJ, Lessells R, Maskew M, Prozesky H, Wood R, Johnson LF, Egger M, Boulle A, and Myer L
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- Adolescent, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections epidemiology, Humans, Male, Middle Aged, Risk Factors, Sex Factors, South Africa epidemiology, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections mortality
- Abstract
Background: Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART., Methods and Findings: Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22-1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12-1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86-1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located., Conclusions: HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors' Summary.
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- 2012
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25. High unreported mortality in children and youth (<25 years) living with HIV who were lost to care from antiretroviral therapy programs in Southern Africa: results from a multi-country tracing study
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Nyakato, Patience, Christ, Benedikt, Anderegg, Nanina, Muhairwe, Josephine, Jefferys, Laura, van Dijk, Janneke, Vinikoor, Michael J, van Lettow, Monique, Chimbetete, Cleophas, Phiri, Sam J, Egger, Matthias, Ballif, Marie, Yiannoutsos, Constantin T, Schomaker, Michael, Kassanjee, Reshma, Davies, Mary-Ann, and Cornell, Morna
- Subjects
Adolescent ,Anti-HIV Agents ,Infant ,HIV Infections ,610 Medicine & health ,Africa, Southern ,Young Adult ,Infectious Diseases ,Anti-Retroviral Agents ,360 Social problems & social services ,Humans ,Pharmacology (medical) ,Lost to Follow-Up ,Child ,Proportional Hazards Models - Abstract
BACKGROUND Antiretroviral therapy (ART) program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS Among 680 children and youth aged
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- 2022
26. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study
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Wang, Qing, De Luca, Andrea, Smith, Colette, Zangerle, Robert, Sambatakou, Helen, Bonnet, Fabrice, Smit, Colette, Schommers, Philipp, Thornton, Alicia, Berenguer, Juan, Peters, Lars, Spagnuolo, Vincenzo, Ammassari, Adriana, Antinori, Andrea, Roldan, Eugenia Quiros, Mussini, Cristina, Miro, Jose M., Konopnicki, Deborah, Fehr, Jan, Campbell, Maria A., Termote, Monique, Bucher, Heiner C., De Wit, Stéphane, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Castagna, Antonella, Del Amo, Julia, Mocroft, Amanda, Raben, Dorthe, Chêne, Geneviève, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Sabin, Caroline, Gibb, Diana, Fätkenheuer, Gerd, Obel, Niels, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, D'Arminio Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Rauch, Andri, Tookey, Pat, Casabona, Jordi, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Judd, Ali, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Wyss, Natasha, Barger, Diana, Schwimmer, Christine, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Wang, Q, De Luca, A, Smith, C, Zangerle, R, Sambatakou, H, Bonnet, F, Smit, C, Schommers, P, Thornton, A, Berenguer, J, Peters, L, Spagnuolo, V, Ammassari, A, Antinori, A, Roldan, E, Mussini, C, Miro, J, Konopnicki, D, Fehr, J, Campbell, M, Termote, M, Bucher, H, Puoti, M, University of Zurich, Bucher, Heiner C, Quiros Roldan, E, Miro, Jm, Campbell, Ma, Bucher, Hc, on behalf of The Hepatitis Coinfection and Non Hodgkin Lymphoma project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, and Castagna, Antonella
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Male ,Lymphoma ,Hepatitis B Surface Antigen ,HIV Infections ,medicine.disease_cause ,Cohort Studies ,10234 Clinic for Infectious Diseases ,0302 clinical medicine ,Risk Factors ,HIV Infection ,030212 general & internal medicine ,Viral ,Chronic ,media_common ,Incidence (epidemiology) ,Hepatitis B Core Antigen ,Lymphoma, Non-Hodgkin ,Hazard ratio ,virus diseases ,General Medicine ,Hepatitis C ,Hepatitis B ,Hepatitis B Core Antigens ,Hepatitis Antibodie ,030220 oncology & carcinogenesis ,RNA, Viral ,Female ,hepatitis c and b ,Cohort study ,Human ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,Biomarkers ,Hepatitis Antibodies ,Hepatitis B Surface Antigens ,Hepatitis B, Chronic ,Hepatitis C, Chronic ,Humans ,Immunoglobulin G ,Hepatitis C virus ,Non-Hodgkin ,610 Medicine & health ,Settore MED/17 - MALATTIE INFETTIVE ,03 medical and health sciences ,Internal medicine ,Internal Medicine ,medicine ,media_common.cataloged_instance ,HIV HCV NHL HBV ,European union ,Hepatitis B virus ,business.industry ,Risk Factor ,Anti-HIV Agent ,Biomarker ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,medicine.disease ,digestive system diseases ,2724 Internal Medicine ,Immunology ,RNA ,Cohort Studie ,business - Abstract
Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.
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- 2017
27. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: A multinational, multicohort European study
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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
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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
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- 2017
28. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers
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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)
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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.
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- 2017
29. Anti-V3/Glycan and Anti-MPER Neutralizing Antibodies, but Not Anti-V2/Glycan Site Antibodies, Are Strongly Associated with Greater Anti-HIV-1 Neutralization Breadth and Potency.
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Jacob, Rajesh Abraham, Moyo, Thandeka, Schomaker, Michael, Abrahams, Fatima, Pujol, Berta Grau, and Dorfman, Jeffrey R.
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IMMUNOGLOBULINS , *GLYCANS , *ANTI-HIV agents , *NEUTRALIZATION (Chemistry) , *ANTIGENS - Abstract
The membrane-proximal external region (MPER), the V2/glycan site (initially defined by PG9 and PG16 antibodies), and the V3/glycans (initially defined by PGT121-128 antibodies) are targets of broadly neutralizing antibodies and potential targets for anti-HIV-1 antibody-based vaccines. Recent evidence shows that antibodies with moderate neutralization breadth are frequently attainable, with 50% of sera from chronically infected individuals neutralizing>50% of a large, diverse set of viruses. Nonetheless, there is little systematic information addressing which specificities are preferentially targeted among such commonly found, moderately broadly neutralizing sera. We explored associations between neutralization breadth and potency and the presence of neutralizing antibodies targeting the MPER, V2/glycan site, and V3/glycans in sera from 177 antiretroviral-naive HIV-1-infected (>1 year) individuals. Recognition of both MPER and V3/glycans was associated with increased breadth and potency. MPER-recognizing sera neutralized 4.62 more panel viruses than MPER-negative sera (95% prediction interval [95% PI], 4.41 to 5.20), and V3/glycan-recognizing sera neutralized 3.24 more panel viruses than V3/glycan-negative sera (95% PI, 3.15 to 3.52). In contrast, V2/glycan site-recognizing sera neutralized only 0.38 more panel viruses (95% PI, 0.20 to 0.45) than V2/glycan site-negative sera and no association between V2/glycan site recognition and breadth or potency was observed. Despite autoreactivity of many neutralizing antibodies recognizing MPER and V3/glycans, antibodies to these sites are major contributors to neutralization breadth and potency in this cohort. It may therefore be appropriate to focus on developing immunogens based upon the MPER and V3/glycans. [ABSTRACT FROM AUTHOR]
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- 2015
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30. Convergence of Mortality Rates among Patients on Antiretroviral Therapy in South Africa and North America
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Susana Monge, Jodie L. Guest, M. John Gill, Daniela Garone, James Ndirangu, Kathrin Ehren, Colin Campbell, Robert S. Hogg, Matthew P. Fox, Olivia Keiser, Jonathan A C Sterne, Heidi M. Crane, Amy C. Justice, Michael S. Saag, Antonella Castagna, Dominique Costagliola, Michael Schomaker, Janet Giddy, Suzanne M Ingle, Fiona C Lampe, Andrew Boulle, Peter Reiss, Bryan E. Shepherd, François Dabis, Margaret T May, Matthias Egger, Boulle, Andrew, Schomaker, Michael, May, Margaret T., Hogg, Robert S., Shepherd, Bryan E., Monge, Susana, Keiser, Olivia, Lampe, Fiona C., Giddy, Janet, Ndirangu, Jame, Garone, Daniela, Fox, Matthew, Ingle, Suzanne M., Reiss, Peter, Dabis, Francoi, Costagliola, Dominique, Castagna, Antonella, Ehren, Kathrin, Campbell, Colin, Gill, M. John, Saag, Michael, Justice, Amy C., Guest, Jodie, Crane, Heidi M., Egger, Matthia, Sterne, Jonathan A. C., Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, Department of Public Health and Family Medicine, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Global Health
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Male ,Viral Diseases ,Epidemiology ,lcsh:Medicine ,HIV Infections ,Plant Science ,Global Health ,Biochemistry ,Cohort Studies ,South Africa ,Antiretroviral Therapy, Highly Active ,Case fatality rate ,Medicine and Health Sciences ,Medicine ,Public and Occupational Health ,Viral load ,HIV Infection ,Prospective Studies ,Cooperative Behavior ,education.field_of_study ,Death rates ,Mortality rate ,General Medicine ,Middle Aged ,Antiretroviral therapy ,3. Good health ,AIDS ,Europe ,Infectious Diseases ,Cohort ,Female ,Developed country ,Research Article ,Human ,Biotechnology ,Cohort study ,Adult ,Anti-HIV Agents ,Population ,Sexually Transmitted Diseases ,Developing country ,610 Medicine & health ,Infectious Disease Epidemiology ,Follow-Up Studie ,Acquired immunodeficiency syndrome (AIDS) ,360 Social problems & social services ,parasitic diseases ,Humans ,Mortality ,education ,Molecular Biology ,business.industry ,lcsh:R ,Biology and Life Sciences ,HIV ,Anti-HIV Agent ,Cell Biology ,Plant Pathology ,medicine.disease ,Social Epidemiology ,Prospective Studie ,North America ,HIV-1 ,Cohort Studie ,business ,Follow-Up Studies ,Demography - Abstract
Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary, Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count, Editors' Summary Background AIDS has killed about 36 million people since the first recorded case of the disease in 1981, and a similar number of people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other serious infections. Early in the AIDS epidemic, HIV-positive people usually died within 10 years of becoming infected. In 1996, effective antiretroviral therapy (ART) became available and, for people living in high-income countries, HIV infection became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. Then, in 2003, the international community began to work towards achieving universal access to ART. By the end of 2012, nearly two-thirds of HIV-positive people (nearly 10 million individuals) living in low- and middle-income countries who were eligible for treatment because their CD4 cell count had fallen below 350/mm3 blood or because they had developed an AIDS-defining condition were receiving treatment. Why Was This Study Done? It is known that a larger proportion of HIV-positive patients starting ART die during the first year of treatment in sub-Saharan Africa than in Europe and North America. This difference arises in part because patients in resource-limited settings tend to have lower CD4 counts when they start treatment than patients in wealthy countries. However, the lack of reliable data on mortality (death) in resource-limited settings has made it hard to compare longer-term outcomes in different settings. Information on the long-term outcomes of HIV-positive patients receiving ART in resource-limited countries is needed to guide the development of appropriate health systems and treatment regimens in these settings. In this collaborative analysis of prospective cohort studies, the researchers compare mortality up to 4 years on ART in South Africa, Europe, and North America. A prospective cohort study follows a group of individuals over time to see whether differences in specific characteristics at the start of the study affect subsequent outcomes. A collaborative analysis combines individual patient data from several studies. What Did the Researchers Do and Find? The researchers combined data from four South Africa cohorts of HIV-positive patients starting ART included in the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration with data from six North American cohorts and nine European cohorts included in the ART Cohort Collaboration (ART-CC). The South African cohorts were chosen because unusually for studies undertaken in countries in sub-Saharan Africa the vital status of patients (whether they had died) who had been lost to follow-up in these cohorts could be obtained from the national population register. Patients in South Africa began treatment with more advanced disease (indicated by a lower average CD4 count) than patients in Europe or North America. Notably, high early mortality after starting ART in South Africa occurred mainly in patients starting ART with a CD4 count below 50 cells/mm3. The cumulative mortality after 4 years of ART was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. After adjusting for patient characteristics at ART initiation, the mortality rate among patients beginning ART was initially lower in Europe and North American than in South Africa. However, although the adjusted mortality rate in Europe remained lower than the rate in South Africa, the rate in North America was higher than that in South Africa between 24 and 48 months on ART. What Do These Findings Mean? Although the linkage to national vital registration systems (databases of births and deaths) undertaken in this collaborative analysis is likely to have greatly reduced bias due to under-ascertainment of mortality, the accuracy of these findings may still be limited by differences in how this linkage was undertaken in different settings. Nevertheless, these findings suggest that mortality among HIV-infected patients receiving ART in South Africa, although initially higher than in Europe and North America, rapidly declines with increasing duration on ART and, after 4 years of treatment, approaches the rate seen in high-income settings. Intriguingly, these findings also highlight the relatively higher late mortality in North America compared to either Europe or South Africa, a result that needs to be investigated to explore the extent to which differences in mortality ascertainment, patient characteristics and comorbidities, or health systems and treatment regimens contribute to variations in outcomes among HIV-positive patients in various settings. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001718. This study is further discussed in a PLOS Medicine Perspective by Agnes Binagwaho and colleagues Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART, on HIV and AIDS in sub-Saharan Africa, and on HIV and AIDS in South Africa (in English and Spanish) The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infections: recommendations for a public health approach are available The 2013 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it Information about the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration and about the ART Cohort Collaboration is available Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
- Published
- 2014
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