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1. Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy

Author

Cain, Lauren E, Saag, Michael S, Petersen, Maya, May, Margaret T, Ingle, Suzanne M, Logan, Roger, Robins, James M, Abgrall, Sophie, Shepherd, Bryan E, Deeks, Steven G, Gill, M John, Touloumi, Giota, Vourli, Georgia, Dabis, François, Vandenhende, Marie-Anne, Reiss, Peter, van Sighem, Ard, Samji, Hasina, Hogg, Robert S, Rybniker, Jan, Sabin, Caroline A, Jose, Sophie, del Amo, Julia, Moreno, Santiago, Rodríguez, Benigno, Cozzi-Lepri, Alessandro, Boswell, Stephen L, Stephan, Christoph, Pérez-Hoyos, Santiago, Jarrin, Inma, Guest, Jodie L, Monforte, Antonella D’Arminio, Antinori, Andrea, Moore, Richard, Campbell, Colin NJ, Casabona, Jordi, Meyer, Laurence, Seng, Rémonie, Phillips, Andrew N, Bucher, Heiner C, Egger, Matthias, Mugavero, Michael J, Haubrich, Richard, Geng, Elvin H, Olson, Ashley, Eron, Joseph J, Napravnik, Sonia, Kitahata, Mari M, Van Rompaey, Stephen E, Teira, Ramón, Justice, Amy C, Tate, Janet P, Costagliola, Dominique, Sterne, Jonathan AC, Hernán, Miguel A, and Systems, and the HIV-CAUSAL Collaboration on behalf of the Antiretroviral Therapy Cohort Collaboration the Centers for AIDS Research Network of Integrated Clinical

Subjects
Epidemiology, Health Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Sexually Transmitted Infections, HIV/AIDS, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Observational Studies as Topic, Randomized Controlled Trials as Topic, Survival Analysis, United Kingdom, Viral Load, HIV, antiretroviral therapy, inverse-probability weighting, observational studies, mortality, dynamic strategies, Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems, and the HIV-CAUSAL Collaboration, Statistics, Public Health and Health Services, Public health
Abstract

BackgroundWhen a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).MethodsWe review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.ResultsOf 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.ConclusionsAlthough our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

Published
2016

2. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries

Author

Caniglia, Ellen C, Sabin, Caroline, Robins, James M, Logan, Roger, Cain, Lauren E, Abgrall, Sophie, Mugavero, Michael J, Hernandez-Diaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Dabis, Francois, Moore, Richard R, Reiss, Peter, van Sighem, Ard, Mathews, William C, del Amo, Julia, Moreno, Santiago, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Olson, Ashley, Justice, Amy C, Tate, Janet P, Bucher, Heiner C, Egger, Matthias, Touloumi, Giota, Sterne, Jonathan A, Costagliola, Dominique, Saag, Michael, and Hernán, Miguel A

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Infectious Diseases, Clinical Research, HIV/AIDS, Prevention, Infection, Good Health and Well Being, AIDS-Related Complex, Anti-HIV Agents, CD4 Lymphocyte Count, Cohort Studies, Developed Countries, Europe, HIV Infections, Humans, Prospective Studies, RNA, Viral, United States, Viral Load, HIV, CD4 cell count, HIV RNA, monitoring, observational studies, mortality, Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration, Clinical Sciences, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract

ObjectiveTo illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).DesignProspective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems.MethodsAntiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes.ResultsIn 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies.ConclusionsOur findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Published
2016

3. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

Author

Caniglia, Ellen C, Sabin, Caroline, Robins, James M, Logan, Roger, Cain, Lauren E, Abgrall, Sophie, Mugavero, Michael J, Hernandez-Diaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Dabis, Francois, Moore, Richard R, Reiss, Peter, van Sighem, Ard, Mathews, William C, Del Amo, Julia, Moreno, Santiago, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Olson, Ashley, Justice, Amy C, Tate, Janet P, Bucher, Heiner C, Egger, Matthias, Touloumi, Giota, Sterne, Jonathan A, Costagliola, Dominique, Saag, Michael, Hernán, Miguel A, and Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration

Subjects
Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration, Humans, HIV Infections, AIDS-Related Complex, RNA, Viral, Anti-HIV Agents, CD4 Lymphocyte Count, Viral Load, Cohort Studies, Prospective Studies, Developed Countries, United States, Europe, HIV, CD4 cell count, HIV RNA, monitoring, observational studies, mortality, RNA, Viral, Virology, Clinical Sciences, Public Health and Health Services
Abstract

ObjectiveTo illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).DesignProspective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems.MethodsAntiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes.ResultsIn 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies.ConclusionsOur findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Published
2016

4. A systematic review of definitions of extreme phenotypes of HIV control and progression.

Author

Gurdasani, Deepti, Iles, Louise, Dillon, David, Young, Elizabeth, Olson, Ashley, Naranbhai, Vivek, Fidler, Sarah, Gkrania-Klotsas, Effrossyni, Post, Frank, Kellam, Paul, Porter, Kholoud, and Sandhu, Manjinder

Subjects
Disease Progression, HIV Infections, HIV Long-Term Survivors, Humans, Phenotype, Terminology as Topic
Abstract

The study of individuals at opposite ends of the HIV clinical spectrum can provide invaluable insights into HIV biology. Heterogeneity in criteria used to define these individuals can introduce inconsistencies in results from research and make it difficult to identify biological mechanisms underlying these phenotypes. In this systematic review, we formally quantified the heterogeneity in definitions used for terms referring to extreme phenotypes in the literature, and identified common definitions and components used to describe these phenotypes. We assessed 714 definitions of HIV extreme phenotypes in 501 eligible studies published between 1 January 2000 and 15 March 2012, and identified substantial variation among these. This heterogeneity in definitions may represent important differences in biological endophenotypes and clinical progression profiles of individuals selected by these, suggesting the need for harmonized definitions. In this context, we were able to identify common components in existing definitions that may provide a framework for developing consensus definitions for these phenotypes in HIV infection.

Published
2014

5. HIV incidence in the Estonian population in 2013 determined using the HIV-1 limiting antigen avidity assay

Author

Soodla, P., Simmons, R., Huik, K., Pauskar, M., Jõgeda, E. -L., Rajasaar, H., Kallaste, E., Maimets, M., Avi, R., Murphy, G., Porter, K., Lutsar, I., Del Amo, Julia, Meyer, Laurence, Bucher, Heiner C., Chêne, Geneviève, Hamouda, Osamah, Pillay, Deenan, Prins, Maria, Rosinska, Magda, Sabin, Caroline, Touloumi, Giota, Olson, Ashley, Cartier, Andrea, Fradette, Lorraine, Walker, Sarah, Babiker, Abdel, De Luca, Andrea, Fisher, Martin, Muga, Roberto, Kelleher, Tony, Cooper, David, Grey, Pat, Finlayson, Robert, Bloch, Mark, Ramacciotti, Tim, Gelgor, Linda, Smith, Don, Zangerle, Robert, Gill, John, Dabis, Francois, Thiebaut, Rodolphe, Costagliola, Dominique, Guiguet, Marguerite, Vanhems, Philippe, Chaix, Marie-Laure, Ghosn, Jade, Boufassa, Faroudy, Meixenberger, Karolin, Bannert, Norbert, Bartmeyer, Barbara, Antoniadou, Anastasia, Chrysos, Georgios, Daikos, Georgios L., Pantazis, Nikos, Katsarou, Olga, Rezza, Giovanni, Dorrucci, Maria, Monforte, Antonella d'Arminio, Geskus, Ronald, van der Helm, Jannie, Schuitemaker, Hanneke, Sannes, Mette, Brubakk, Oddbjorn, Kran, Anne-Marte Bakken, Rosinska, Magdalena, Tor, Jordi, de Olalla, Patricia Garcia, Cayla, Joan, Moreno, Santiago, Monge, Susana, del Romero, Jorge, Pérez-Hoyos, Santiago, Sönnerborg, Anders, Günthard, Huldrych, Scherrer, Alexandra, Malyuta, Ruslan, Johnson, Anne, Phillips, Andrew, Morrison, Charles, Price, Matt A., Giaquinto, Carlo, Grarup, Jesper, Kirk, Ole, Bailey, Heather, Volny Anne, Alain, Panteleev, Alex, Thorne, Claire, Aboulker, Jean-Pierre, Albert, Jan, Asandi, Silvia, De Wit, Stéphane, Reiss, Peter, Gatell, José, Karpov, Igor, Ledergerber, Bruno, Møller, Claus, Rakhmanova, Aza, Rockstroh, Jürgen, Sandhu, Manjinder, Dedes, Nikos, Pizzuti, David, Faggion, Silvia, Raben, Dorthe, Schwimmer, Christine, Scott, Martin, APH - Global Health, Infectious diseases, Epidemiology and Data Science, Experimental Immunology, APH - Aging & Later Life, and Global Health

Subjects
Male, 0301 basic medicine, HIV Infections, Immunoenzyme Techniques, 0302 clinical medicine, Epidemiology, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, media_common, Aged, 80 and over, education.field_of_study, Transmission (medicine), Incidence, Health Policy, Incidence (epidemiology), virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Female, epidemiology, Viral load, Adult, Estonia, medicine.medical_specialty, Adolescent, 030106 microbiology, Population, Eastern Europe, recent infection testing algorithm, Young Adult, recent HIV infection, 03 medical and health sciences, Internal medicine, medicine, Humans, HIV serological assay, media_common.cataloged_instance, European union, Seroconversion, education, Aged, injecting drug users, Diagnostic Tests, Routine, business.industry, Public health, HIV, Immunology, HIV-1, business
Abstract

OBJECTIVES: Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. METHODS: All individuals aged ≥18 years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. RESULTS: Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33 years (IQR: 28–42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. CONCLUSIONS: These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaigns.

Published
2017

6. Limiting Cumulative HIV Viremia Copy-Years by Early Treatment Reduces Risk of AIDS and Death

Author

Olson, Ashley D., Walker, A. Sarah, Suthar, Amitabh B., Sabin, Caroline A., Bucher, Heiner C., Jarrín, Inmaculada, Moreno, Santiago, Pérez-Hoyos, Santiago, Porter, Kholoud, Ford, Deborah, Universitat Autònoma de Barcelona, Unión Europea. Comisión Europea. 7 Programa Marco, and Medical Research Council (Reino Unido)

Subjects
0301 basic medicine, Cart, Adult, Male, medicine.medical_specialty, Adolescent, Viremia copy-years, Human immunodeficiency virus (HIV), CD4 cell count, Viremia, HIV Infections, medicine.disease_cause, when to start, 03 medical and health sciences, Young Adult, cART initiation, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), When to start, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Young adult, Seroconversion, seroconverters, viremia copy-years, Acquired Immunodeficiency Syndrome, business.industry, Proportional hazards model, Hazard ratio, CART initiation, virus diseases, Epidemiology and Prevention, Middle Aged, medicine.disease, 030112 virology, 3. Good health, CD4 Lymphocyte Count, Seroconverters, Infectious Diseases, HIV-RNA, Immunology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, business
Abstract

Supplemental Digital Content is Available in the Text., Background: Viremia copy-years (VCY), a time-updated measure of cumulative HIV exposure, predicts AIDS/death; although its utility in deciding when to start combination antiretroviral therapy (cART) remains unclear. We aimed to assess the impact of initiating versus deferring cART on risk of AIDS/death by levels of VCY both independent of and within CD4 cell count strata ≥500 cells per cubic millimeter. Methods: Using Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) data, we created a series of nested “trials” corresponding to consecutive months for individuals ≥16 years at seroconversion after 1995 who were cART-naive and AIDS-free. Pooling across all trials, time to AIDS/death by CD4, and VCY strata was compared in those initiating vs. deferring cART using Cox models adjusted for: country, sex, risk group, seroconversion year, age, time since last HIV-RNA, and current CD4, VCY, HIV-RNA, and mean number of previous CD4/HIV-RNA measurements/year. Results: Of 9353 individuals, 5312 (57%) initiated cART and 486 (5%) acquired AIDS/died. Pooling CD4 strata, risk of AIDS/death associated with initiating vs. deferring cART reduced as VCY increased. In patients with high CD4 cell counts, ≥500 cells per cubic millimeter, there was a trend for a greater reduction for those initiating vs. deferring with increasing VCY (P = 0.09), with the largest benefit in the VCY ≥100,000 copy-years/mL group [hazard ratio (95% CI) = 0.41 (0.19 to 0.87)]. Conclusions: For individuals with CD4 ≥500 cells per cubic millimeter, limiting the cumulative HIV burden to

Published
2016

7. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment

Author

Pantazis, Nikos, Touloumi, Giota, Meyer, Laurence, Olson, Ashley, Costagliola, Dominique, Kelleher, Anthony D, Lutsar, Irja, Chaix, Marie-Laure, Fisher, Martin, Moreno, Santiago, Porter, Kholoud, Department of Hygiene, Epidemiology and Medical Statistics [Athens], University of Athens Medical School [Athens], 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), Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Kirby Institute for Infection and Immunity in Society (UNSW), University of New South Wales [Sydney] (UNSW), Department of Microbiology, University of Tartu, Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), HIV/GUM Research [Brigton], Brighton and Sussex University Hospitals - NHS Trust (BSUH), Infectious Diseases Department [Madrid], Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH)-Universidad de Alcalá - University of Alcalá (UAH), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and d'Eggis, Gilles

Subjects
Adult, Male, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adolescent, Anti-HIV Agents, virus diseases, HIV, HIV Infections, Middle Aged, Viral Load, virologic response, CD4 Lymphocyte Count, Europe, Young Adult, Treatment Outcome, Withholding Treatment, Antiretroviral Therapy, Highly Active, immunologic response, Humans, Female, Longitudinal Studies, early/primary HIV infection, treatment reinitiation, transient combination antiretroviral treatment, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI).Design: Longitudinal observational study.Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models.Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (~80 cells/µl; P < 0.001) and retained significantly higher CD4+ cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+ cell count, differences in CD4+ cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment.Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

Published
2016

8. Children and young people with perinatal HIV in Europe: epidemiological situation in 2014 and implications for the future

Author

del Amo, Julia, Conejo, Pablo Rojo, Sabin, Caroline, Warszawski, Josiane, Gennotte, Anne-Francoise, Nadal, David, Gibb, Diana, Judd, Ali, Thorne, Claire, Olson, Ashley, Lodi, Sara, Pantazis, Nikos, Termote, Monique, Ledergerber, Bruno, Kristensen, Dennis, Brandt, Rikke Salbøl, Saidi, Yacine, Burns, Fiona, Chêne, Geneviève, Costagliola, Dominique, Giaquinto, Carlo, Grarup, Jesper, Kirk, Ole, Meyer, Laurence, Bailey, Heather, Anne, Alain Volny, Panteleev, Alex, Phillips, Andrew, Porter, Kholoud, Aboulker, Jean-Pierre, Albert, Jan, Asandi, Silvia, Monforte, Antonella d'Arminio, de Wit, Stéphane, Reiss, Peter, Gatell, José, Clínic, Fundació Privada, Bíomèdica, Recerca, Hamouda, Osamah, Karpov, Igor, Lundgren, Jens, Malyuta, Ruslan, Møller, Claus, Prins, Maria, Rakhmanova, Aza, Rockstroh, Jürgen, Rosinska, Magda, Sandhu, Manjinder, Touloumi, Giota, Cooper, David, Global Health, and Infectious diseases

Subjects
Adult, medicine.medical_specialty, Adolescent, Epidemiology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Perinatal hiv, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Virology, Environmental health, Surveys and Questionnaires, Journal Article, Medicine, Humans, 030212 general & internal medicine, 030505 public health, business.industry, Research Support, Non-U.S. Gov't, Public Health, Environmental and Occupational Health, Infant, Newborn, Infectious Disease Transmission, Vertical, Europe, Cohort, Female, 0305 other medical science, business
Abstract

Accurate ascertainment of the number of children living with human immunodeficiency virus (HIV) is important to plan paediatric and adolescent health services. In Europe, the first generation of perinatally HIV-infected survivors are transferring to adult care and their health needs are unknown. We undertook an online survey of HIV cohort studies participating in the EuroCoord Network of Excellence to ascertain the number of perinatally HIV-infected (pHIV) patients included, to compare it with those published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) and to assess the ability of countries to follow up pHIV patients after transfer to adult care. At the end of 2013, 16 countries in EuroCoord reported 8,229 pHIV patients in follow-up in cohorts, compared with 5,160 cumulative diagnoses reported by the ECDC in the same area. Follow-up of pHIV patients after transfer to adult care varied. It is likely that the number of diagnoses of perinatal HIV reported to ECDC is an underestimate, although this varies by country. Further work is needed to refine estimates and encourage follow-up in adult HIV cohorts to investigate long-term outcomes and improve the care of the next generation of children with HIV.

Published
2015

9. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Author

The HIV-CAUSAL Collaboration, Lodi, Sara, del Amo, Julia, Moreno, Santiago, Bucher, Heiner C, Furrer, Hansjakob, Logan, Roger, Sterne, Jonathan, Pérez-Hoyos, Santiago, Jarrín, Inma, Phillips, Andrew, Olson, Ashley, van Sighem, Ard, Reiss, Peter, Sabin, Caroline, Jose, Sophie, Justice, Amy, Goulet, Joseph, Miró, José M, Ferrer, Elena, Meyer, Laurence, Seng, Rémonie, Vourli, Georgia, Antoniadou, Anastasia, Dabis, Francois, Vandenhede, Mari-Anne, Costagliola, Dominique, Abgrall, Sophie, and Hernán, Miguel A

Subjects
Adult, Male, Adolescent, Lymphoma, Antiretroviral Therapy, HIV Infections, Medical and Health Sciences, Young Adult, Rare Diseases, Neoplasms, Virology, Behavioral and Social Science, Genetics, Humans, Tuberculosis, Highly Active, unmasking, Aged, Cancer, AIDS-Related Opportunistic Infections, Incidence, Developed Countries, Psychology and Cognitive Sciences, virus diseases, HIV, Hematology, Middle Aged, Biological Sciences, immune reconstitution inflammatory syndrome, United States, Europe, Infectious Diseases, Good Health and Well Being, Anti-Retroviral Agents, HIV/AIDS, Female, Infection, inverse probability weighting
Abstract

BackgroundThere is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.MethodsWe identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, had CD4 cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4 cell count and HIV-RNA via inverse probability weighting.ResultsOut of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.ConclusionWith the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Published
2014

10. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Author

Lodi, Sara, Del Amo, Julia, Moreno, Santiago, Bucher, H. C., Furrer, Hansjakob, Logan, Roger, Sterne, Jonathan, Pérez-Hoyos, Santiago, Jarrín, Inma, Phillips, Andrew, Olson, Ashley, Van Sighem, Ard, Reiss, Peter, Sabin, C., Jose, Sophie, Justice, Amy, Goulet, Joseph, Miró, José M., Ferrer, Elena, Meyer, Laurence, Seng, Rémonie, Vourli, Georgia, Antoniadou, Anastasia, Dabis, Francois, Vandenhede, Mari Anne, Costagliola, Dominique, Abgrall, S., Hernán, Miguel A., Hernan, Miguel, Bansi, L., Hill, T., Dunn, D., Porter, K., Glabay, A., Orkin, C., Thomas, R., Jones, K., Fisher, M., Perry, N., Pullin, A., Churchill, D., Gazzard, B., Nelson, M., Asboe, D., Bulbeck, S., Mandalia, S., Clarke, J., Delpech, V., Anderson, J., Munshi, S., Post, F., Easterbrook, P., Khan, Y., Patel, P., Karim, F., Duffell, S., Gilson, R., Man, S. L., Williams, I., Gompels, M., Dooley, D., Schwenk, A., Ainsworth, J., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Ismajani Puradiredja, D., Phillips, A., Walsh, J., Weber, J., Kemble, C., Mackie, N., Winston, A., Leen, C., Wilson, A., Bezemer, D. O., Gras, L. A.J., Kesselring, A. M., Van Sighem, A. I., Zaheri, S., Van Twillert, G., Kortmann, W., Branger, J., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T.M., Wit, F. W.M.N., Godfried, M. H., Reiss, P., Van Der Poll, T., Nellen, F. J.B., Lange, J. M.A., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Van Der Valk, M., Grijsen, M. L., Wiersinga, W. J., Brinkman, K., Blok, W. L., Frissen, P. H.J., Schouten, W. E.M., Van Den Berk, G. E.L., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M.E., Lauw, F. N., Van Eeden, A., Verhagen, D. W.M., Van Agtmael, M. A., Perenboom, R. M., Claessen, F. A.P., Bomers, M., Peters, E. J.G., Richter, C., Van Der Berg, J. P., Gisolf, E. H., Schippers, E. F., Van Nieuwkoop, C., Van Elzakker, E. P., Leyten, E. M.S., Gelinck, L. B.S., Pronk, M. J.H., Bravenboer, B., Kootstra, G. J., Delsing, C. E., Sprenger, H. G., Doedens, R., Scholvinck, E. H., Van Assen, S., Bierman, W. F.W., Soetekouw, R., Ten Kate, R. W., Van Vonderen, M. G.A., Van Houte, D. P.F., Kroon, F. P., Van Dissel, J. T., Arend, S. M., De Boer, M. G.J., Jolink, H., Ter Vollaard, H. J.M., Bauer, M. P., Weijer, S., El Moussaoui, R., Lowe, S., Schreij, G., Oude Lashof, A., Posthouwer, D., Koopmans, P. P., Keuter, M., Van Der Ven, A. J.A.M., Ter Hofstede, H. J.M., Dofferhoff, A. S.M., Warris, A., Van Crevel, R., Van Der Ende, M. E., De Vries-Sluijs, T. E.M.S., Schurink, C. A.M., Nouwen, J. L., Nispen Tot Pannerden, M. H., Verbon, A., Rijnders, B. J.A., Van Gorp, E. C.M., Hassing, R. J., Smeulders, A. W.M., Hartwig, N. G., Driessen, G. J.A., Den Hollander, J. G., Pogany, K., Juttmann, J. R., Van Kasteren, M. E.E., Hoepelman, A. I.M., Mudrikova, T., Schneider, M. M.E., Jaspers, C. A.J.J., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W.M., Barth, R. E., Geelen, S. P.M., Wolfs, T. F.W., Bont, L. J., Van Den Berge, M., Stegeman, A., Groeneveld, P. H.P., Alleman, M. A., Bouwhuis, J. W., Barin, F., Burty, C., Duvivier, C., Enel, P., Fredouille-Heripret, L., Gasnault, J., Khuong, M. A., Mahamat, A., Pilorgé, F., Tattevin, P., Salomon, Valérie, Jacquemet, N., Costagliola, D., Grabar, S., Guiguet, M., Lanoy, E., Lièvre, L., Mary-Krause, M., Selinger-Leneman, H., Lacombe, J. M., Potard, V., Bricaire, F., Herson, S., Katlama, C., Simon, A., Desplanque, N., Girard, P. M., Meynard, J. L., Meyohas, M. C., Picard, O., Cadranel, J., Mayaud, C., Pialoux, G., Clauvel, J. P., Decazes, J. M., Gérard, L., Molina, J. M., Diemer, M., Sellier, P., Bentata, M., Honoré, P., Jeantils, V., Tassi, S., Mechali, D., Taverne, B., Bouvet, E., Crickx, B., Ecobichon, J. L., Matheron, S., Picard-Dahan, C., Yeni, P., Berthé, H., Dupont, C., Chandemerle, C., Mortier, E., De Truchis, P., Tisne-Dessus, D., Weiss, L., Salmon, D., Auperin, I., Gilquin, J., Roudière, L., Viard, J. P., Boue, F., Fior, R., Delfraissy, J. F., Goujard, C., Jung, C., Lesprit, Ph, Vittecoq, D., Fraisse, P., Lang, J. M., Rey, D., Beck-Wirth, G., Stahl, J. P., Lecercq, P., Gourdon, F., Laurichesse, H., Fresard, A., Lucht, F., Bazin, C., Verdon, R., Chavanet, P., Arvieux, C., Michelet, C., Choutet, P., Goudeau, A., Maître, M. F., Hoen, B., Eglinger, P., Faller, J. P., Borsa-Lebas, F., Caron, F., Reynes, J., Daures, J. P., May, T., Rabaud, C., Berger, J. L., Rémy, G., Arlet-Suau, E., Cuzin, L., Massip, P., Thiercelin Legrand, M. F., Pontonnier, G., Viget, N., Yasdanpanah, Y., Dellamonica, P., Pradier, C., Pugliese, P., Aleksandrowicz, K., Quinsat, D., Ravaux, I., Tissot-Dupont, H., Delmont, J. P., Moreau, J., Gastaut, J. A., Poizot Martin, I., Retornaz, F., Soubeyrand, J., Galinier, A., Ruiz, J. M., Allegre, T., Blanc, P. A., Bonnet-Montchardon, D., Lepeu, G., Granet-Brunello, P., Esterni, J. P., Pelissier, L., Cohen-Valensi, R., Nezri, M., Chadapaud, S., Laffeuillade, A., Billaud, E., Raffi, F., Boibieux, A., Peyramond, D., Livrozet, J. M., Touraine, J. L., Cotte, L., Trepo, C., Strobel, M., Bissuel, F., Pradinaud, R., Sobesky, M., Cabié, A., Gaud, C., Contant, M., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Haerry, D., Fux, C. A., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez De Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Casabona, J., Gallois, A., Esteve, A., Podzamczer, D., Murillas, J., Gatell, J. M., Manzardo, C., Tural, C., Clotet, B., Ferrer, E., Riera, M., Segura, F., Navarro, G., Force, L., Vilaró, J., Masabeu, A., García, I., Guadarrama, M., Cifuentes, C., Dalmau, D., Jaen, Agustí, C., Montoliu, A., Pérez, I., Gargoulas, Freyra, Blanco, J. L., Garcia-Alcaide, F., Martínez, E., Mallolas, J., López-Dieguez, M., García-Goez, J. F., Sirera, G., Romeu, J., Jou, A., Negredo, E., Miranda, C., Capitan, M. C., Saumoy, M., Imaz, A., Tiraboschi, J. M., Murillo, O., Bolao, F., Peña, C., Cabellos, C., Masó, M., Vila, A., Sala, M., Cervantes, M., Jose Amengual, Ma, Navarro, M., Penelo, E., Barrufet, P., Bejarano, G., Molina, J., Alvaro, M., Mercadal, J., Fernandez, Juanse, Ospina, Jesus E., Muñoz, M. A., Caro-Murillo, A. M., Sobrino, P., Jarrín, I., Gomez Sirvent, J. L., Rodríguez, P., Aleman, M. R., Alonso, M. M., Lopez, A. M., Hernandez, M. I., Soriano, V., Labarga, P., Barreiro, P., Medrano, J., Rivas, P., Herrero, D., Blanco, F., Vispo, M. E., Martín, L., Ramírez, G., De Diego, M., Rubio, R., Pulido, F., Moreno, V., Cepeda, C., Hervás, Rl, Iribarren, J. A., Arrizabalaga, J., Aramburu, M. J., Camino, X., Rodrí-guez-Arrondo, F., Von Wichmann, M. A., Pascual, L., Goenaga, M. A., Gutierrez, F., Masia, M., Ramos, J. M., Padilla, S., Sanchez-Hellín, V., Bernal, E., Escolano, C., Montolio, F., Peral, Y., Berenguer, J., Lopez, J. C., Miralles, P., Cosín, J., Sanchez, M., Gutierrez, I., Ramírez, M., Padilla, B., Vidal, F., Sanjuan, M., Peraire, J., Veloso, S., Vilades, C., Lopez-Dupla, M., Olona, M., Vargas, M., Aldeguer, J. L., Blanes, M., Lacruz, J., Salavert, M., Montero, M., Cuéllar, S., De Los Santos, I., Sanz, J., Oteo, J. A., Blanco, J. R., Ibarra, V., Metola, L., Sanz, M., Pérez-Martínez, L., Sola, J., Uriz, J., Castiello, J., Reparaz, J., Arriaza, M. J., Irigoyen, C., Moreno, S., Antela, A., Casado, J. L., Dronda, F., Moreno, A., Pérez, M. J., López, D., Gutiérrez, C., Hernández, B., Pumares, M., Martí, P., García, L., Page, C., García, F., Hernández, J., Peña, A., Muñoz, L., Parra, J., Viciana, P., Leal, M., López-Cortés, L. F., Trastoy, M., Mata, R., Justice, A. C., Fiellin, D. A., Rimland, D., Jones-Taylor, C., Oursler, K. A., Titanji, R., Brown, S., Garrison, S., Rodriguez-Barradas, M., Masozera, N., Goetz, M., Leaf, D., Simberkoff, M., Blumenthal, D., Leung, J., Butt, A., Hoffman, E., Gibert, C., Peck, R., Mattocks, K., Braithwaite, S., Brandt, C., Bryant, K., Cook, R., Conigliaro, J., Crothers, K., Chang, J., Crystal, S., Day, N., Erdos, J., Freiberg, M., Kozal, M., Gandhi, N., Gaziano, M., Gerschenson, M., Good, B., Gordon, A., Goulet, J. L., Hernán, M. A., Kraemer, K., Lim, J., Maisto, S., Miller, P., Mole, L., O'Connor, P., Papas, R., Robins, J. M., Rinaldo, C., Roberts, M., Samet, J., Tierney, B., Whittle, J., Babiker, A., Brettle, R., Darbyshire, J., Goldberg, D., Hawkins, D., Jaffe, H., Johnson, A., McLean, K., Pillay, D., Cursley, Adam, Ewings, Fiona, Fairbrother, Keith, Louisa Gnatiuc, S. L., Murphy, Brendan, Douglas, G., Kennedy, N., Pritchard, J., Andrady, U., Rajda, N., Maw, R., McKernan, S., Drake, S., Gilleran, G., White, D., Ross, J., Toomer, S., Hewart, R., Wilding, H., Woodward, R., Dean, G., Heald, L., Horner, P., Glover, S., Bansaal, D., Eduards, S., Carne, C., Browing, M., Das, R., Stanley, B., Estreich, S., Magdy, A., O'Mahony, C., Fraser, P., Hayman, B., Jebakumar, S. P.R., Joshi, U., Ralph, S., Wade, A., Mette, R., Lalik, J., Summerfield, H., El-Dalil, A., France, J. A., White, C., Robertson, R., Gordon, S., McMillan, S., Morris, S., Lean, C., Vithayathil, K., McLean, L., Winter, A., Gale, D., Jacobs, S., Tayal, S., Short, L., Green, S., Williams, G., Sivakumar, K., Bhattacharyya, N. D., Monteiro, E., Minton, J., Dhar, J., Nye, F., De Souza, C. B., Isaksen, A., McDonald, L., Franca, A., William, L., Jendrulek, I., Peters, B., Shaunak, S., El-Gadi, S., Easterbrook, P. J., Mazhude, C., Johnstone, R., Fakoya, A., McHale, J., Waters, A., Kegg, S., Mitchell, S., Byrne, P., Rice, P., Fidler, S., Mullaney, S. A., McCormack, S., David, D., Melville, R., Phillip, K., Balachandran, T., Mabey-Puttock, S., Sukthankar, A., Murphy, C., Wilkins, E., Ahmad, S., Haynes, J., Evans, E., Ong, E., Grey, R., Meaden, J., Bignell, C., Loay, D., Peacock, K., Girgis, M. R., Morgan, B., Palfreeman, A., Wilcox, J., Tobin, J., Tucker, L., Saeed, A. M., Chen, F., Deheragada, A., Williams, O., Lacey, H., Herman, S., Kinghorn, D., Devendra, V. S., Wither, J., Dawson, S., Rowen, D., Harvey, J., Bridgwood, A., Singh, G., Chauhan, M., Kellock, D., Young, S., Dannino, S., Kathir, Y., Rooney, G., Currie, J., FitzGerald, M., Devendra, S., Keane, F., Booth, G., Green, T., Arumainayyagam, J., Chandramani, S., Rajamanoharan, S., Robinson, T., Curless, E., Gokhale, R., Tariq, A., Luzzi, G., Fairley, I., Wallis, F., Smit, E., Ward, F., Loze, B., Morlat, P., Bonarek, M., Bonnet, F., Nouts, C., Louis, I., Reliquet, V., Sauser, F., Biron, C., Mounoury, O., Hue, H., Brosseau, D., Ghosn, J., Rannou, M. T., Bergmann, J. F., Badsi, E., Rami, A., Parrinello, M., Samanon-Bollens, D., Campa, P., Tourneur, M., Desplanques, N., Jeanblanc, F., Chiarello, P., Makhloufi, D., Blanc, A. P., Allègre, T., Baillat, V., Lemoing, V., Merle De Boever, C., Tramoni, C., Sobesky, G., Abel, S., Beaujolais, V., Slama, L., Chakvetadze, C., Berrebi, V., Fournier, I., Gerbe, J., Koffi, K., Augustin-Normand, C., Miailhes, P., Thoirain, V., Brochier, C., Souala, F., Ratajczak, M., Beytoux, J., Jacomet, C., Rouveix, E., Morelon, S., Olivier, C., Lortholary, O., Dupont, B., Maignan, A., Ragnaud, J. M., Raymond, I., Leport, C., Jadand, C., Jestin, C., Longuet, P., Boucherit, S., Sereni, D., Lascoux, C., Prevoteau, F., Sobel, A., Levy, Y., Lelievre, J. D., Lascaux, A. S., Dominguez, S., Dumont, C., Aumâitre, H., Delmas, B., Saada, M., Medus, M., Guillevin, L., Tahi, T., Yazdanpanah, Y., Pavel, S., Marien, M. C., Drenou, B., Beck, C., Benomar, M., Tubiana, R., Ait Mohand, H., Chermak, A., Ben Abdallah, S., Touam, F., Drobacheff, C., Folzer, A., Obadia, M., Prudhomme, L., Bonnet, E., Balzarin, F., Pichard, E., Chennebault, J. M., Fialaire, P., Loison, J., Galanaud, P., Boué, F., Bornarel, D., Six, M., Ferret, P., Batisse, D., Gonzales-Canali, G., Devidas, A., Chevojon, P., Turpault, I., Lafeuillade, A., Cheret, A., Philip, G., Morel, P., Timsit, J., Amirat, N., Brancion, C., Cabane, J., Tredup, J., Stein, A., Ravault, I., Chavanet, C., Buisson, M., Treuvetot, S., Nau, P., Bastides, F., Boyer, L., Wassoumbou, S., Oksenhendeler, E., Bernard, L., Domart, Y., Merrien, D., Greder Belan, A., Gayraud, M., Bodard, L., Meudec, A., Beuscart, C., Daniel, C., Pape, E., Vinceneux, P., Simonpoli, A. M., Zeng, A., Fournier, L., Fuzibet, J. G., Sohn, C., Rosenthal, E., Quaranta, M., Chaillou, S., Sabah, M., Audhuy, B., Schieber, A., Moreau, P., Niault, M., Vaillant, O., Huchon, G., Compagnucci, A., De Lacroix Szmania, I., Richier, L., Lamaury, I., Saint-Dizier, F., Garipuy, D., Drogoul, M. P., Fabre, G., Lambert De Cursay, G., Abraham, B., Perino, C., Lagarde, P., David, F., Roche-Sicot, J., Saraux, J. L., Leprêtre, A., Fampin, B., Uludag, A., Morin, A. S., Bletry, O., Zucman, D., Regnier, A., Girard, J. J., Quinsat, D. T., Heripret, L., Grihon, F., Houlbert, D., Ruel, M., Chemlal, K., Debab, Y., Tremollieres, F., Perronne, V., Slama, B., Perré, P., Miodovski, C., Guermonprez, G., Dulioust, A., Boudon, P., Malbec, D., Patey, O., Semaille, C., Deville, J., Remy, G., Béguinot, I., Chambrin, V., Pignon, C., Estocq, G. A., Levy, A., Duracinsky, M., Le Bras, P., Ngussan, M. S., Peretti, D., Medintzeff, N., Lambert, T., Segeral, O., Lezeau, P., Laurian, Y., Piketty, C., Karmochkine, M., Eliaszewitch, M., Jayle, D., Kazatchkine, M., Colasante, U., Duval, X., Nouaouia, W., Vilde, J. L., Bollens, D., Binet, D., Diallo, B., Fonquernie, L., Lagneau, J. L., Launay, O., Pietrie, M. P., Sicard, D., Stieltjes, N., Michot, J., Bourdillon, F., Obenga, G., Escaut, L., Bolliot, C., Schneider, L., Iguertsira, M., Tomei, C., Dhiver, C., Tissot Dupont, H., Vallon, A., Gallais, J., Gallais, H., Durant, J., Mondain, V., Perbost, I., Cassuto, J. P., Karsenti, J. M., Venti, H., Ceppi, C., Krivitsky, J. A., Bouchaud, O., Honore, P., Delgado, J., Rouzioux, C., Burgard, M., Boufassa, L., Peynet, J., Pérez-Hoyos, S., Del Amo, J., Alvarez, D., Monge, S., Muga, R., Sanvisens, A., Tor, J., Rivas, I., Vallecillo, G., Del Romero, J., Raposo, P., Rodríguez, C., Vera, M., Hurtado, I., Belda, J., Fernandez, E., Alastrue, I., Santos, C., Tasa, T., Juan, A., Trullen, J., Garcia De Olalla, P., Cayla, J., Masdeu, E., Knobel, H., Mirò, J. M., Sambeat, M. A., Guerrero, R., Rivera, E., Marco, A., Quintana, M., Gonzalez, C., Castilla, J., Guevara, M., De Mendoza, C., Zahonero, N., Ortíz, M., Paraskevis, D., Touloumi, G., Pantazis, N., Bakoyannis, G., Gioukari, V., Antoniadou, A., Papadopoulos, A., Petrikkos, G., Daikos, G., Psichogiou, M., Gargalianos-Kakolyris, P., Xylomenos, G., Katsarou, O., Kouramba, A., Ioannidou, P., Kordossis, T., Kontos, A., Lazanas, M., Chini, M., Tsogas, N., Panos, G., Paparizos, V., Leuow, K., Kourkounti, S., Sambatakou, H., Mariolis, I., Skoutelis, A., Papastamopoulos, V., Baraboutis, I., Internal medicine, APH - Aging & Later Life, Pediatric surgery, CCA - Innovative therapy, ICaR - Circulation and metabolism, ICaR - Ischemia and repair, Graduate School, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Global Health, Center of Experimental and Molecular Medicine, APH - Amsterdam Public Health, AII - Inflammatory diseases, and ARD - Amsterdam Reproduction and Development

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Opportunistic infection, AIDS-Related Opportunistic Infections, Immunology, Population, Retinitis, HIV Infections, Article, 17 Psychology And Cognitive Sciences, Young Adult, Immune reconstitution inflammatory syndrome, Antiretroviral Therapy, Highly Active, Neoplasms, Virology, Internal medicine, medicine, Humans, Immunology and Allergy, education, Inverse probability weighting, Aged, education.field_of_study, business.industry, Developed Countries, Incidence, Progressive multifocal leukoencephalopathy, Hazard ratio, HIV, virus diseases, 11 Medical And Health Sciences, Middle Aged, 06 Biological Sciences, medicine.disease, United States, Europe, Infectious Diseases, Anti-Retroviral Agents, Unmasking, Female, Cytomegalovirus retinitis, business
Abstract

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting.Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Published
2014

11. An Evaluation of HIV Elite Controller Definitions within a Large Seroconverter Cohort Collaboration.

Author

Olson, Ashley D., Meyer, Laurence, Prins, Maria, Thiebaut, Rodolphe, Gurdasani, Deepti, Guiguet, Marguerite, Chaix, Marie-Laure, Amornkul, Pauli, Babiker, Abdel, Sandhu, Manjinder S., and Porter, Kholoud

Subjects
*HIV infections, *THERAPEUTICS, *SEXUALLY transmitted diseases, *PHENOTYPES, *DISEASE progression, *FOLLOW-up studies (Medicine), *CD4 antigen, *LONG-term non-progressors
Abstract

Background: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. Methods: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). Results: Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm3. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up≥ six months, or with 90% of measurements <400 copies/ml over ≥10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5–19.0 for non-ECs compared to ECs). Conclusions: ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥10 years be used to define this phenotype. [ABSTRACT FROM AUTHOR]

Published
2014
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12. The importance of viral blips and duration of therapy initiated in primary infection in maintaining viral control after stopping cART.

Author

Fidler, Sarah, Olson, Ashley, Fox, Julie, Phillips, Andrew, Morrison, Charles, Thornhill, John, Bucher, Heiner, Muga, Roberto, and Porter, Kholoud

Subjects
*VIRAL load, *HIV infections, *HIV-positive persons, *THERAPEUTICS, *RNA
Abstract

Introduction After achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA rebounds to pre-treatment values for the majority due to the presence of an inaccessible viral reservoir. There is some evidence that cART during primary HIV infection (PHI) limits the reservoir size, optimizing the chance of maintaining viral control off cART. Data are required to predict possible viral controllers for treatment interruption following cART. This analysis aims to investigate the effect of cART duration and the rate of viral blips while on cART initiated in PHI, and other factors on maintaining viral control for those stopping cART. Material and Methods Using CASCADE data on HIV seroconverters, we characterized virologic blip (viral suppression on cART followed by a single HIV-RNA above a blip threshold and a subsequent measure below the threshold without cART change) rates for those starting cART within six months of seroconversion (SC). Using Cox models, we examined the effect of the following factors on time to virologic rebound (HIV-RNA>1000) after cART stop: cART duration, severity/rate of blips on cART, time from SC to cART start, cART class, SC year, SC age, CD4 at cART start/stop, sex and HIV risk group. Results The 660 individuals initiating cART in PHI were mostly male (91%), seroconverting between 1995 and 2012, with a median (IQR) age of 34 (29, 41) years mostly infected through sex between men (73%). Median cART duration was 14.8 (7.0, 31.7) months initiated at a median 1.9 (0.5, 3.9) months post SC. 13 (11, 16), 9 (7, 11), 6 (5, 9) and 7 (6, 10)% of individuals experienced blips >50, 100, 200 and 400 copies/mL, respectively. Of those who experienced blips, most (77-90%, depending on blip threshold) experienced just one. Among 250 individuals with undetectable HIV-RNA at cART stop, median time to rebound was 1.6 (0.30, 5.8) months. Time on cART was the only factor independently associated with control after stopping, HR for rebound=0.91 (0.86, 0.98) per extra six months spent on cART, HR for ever blipping >400 copies/mL while on cART=0.88 (0.40, 1.93). Conclusions Blips occur in about 10% of individuals who initiate cART in PHI, most of who experience only one blip, but was not predictive of subsequent virologic rebound. Increasing time spent on cART initiated in PHI could increase time of virological suppression after cART stop. [ABSTRACT FROM AUTHOR]

Published
2014
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