Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

Clinical Infectious Diseases, May 2016

Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996–1997, 1998–1999, 2000–2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years’ duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts.

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Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

CID Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study Margaret T. May 15 Jorg-Janne Vehreschild 14 Adam Trickey 15 Niels Obel 12 Peter Reiss 19 20 Fabrice Bonnet 17 18 Murielle Mary-Krause 22 Hasina Samji 21 Matthias Cavassini 16 Michael John Gill 9 Leah C. Shepherd 10 Heidi M. Crane 7 Antonella d'Arminio Monforte 8 Greer A. Burkholder 5 Margaret M. Johnson 6 Paz Sobrino-Vegas 2 Pere Domingo 4 Robert Zangerle 0 Amy C. Justice 11 13 Timothy R. Sterling 1 José M. Miró 3 Jonathan A. C. Sterne 15 for the Antiretroviral Therapy Cohort Collaboration (ART-CC) 0 Medical University Innsbruck , Austria 1 Vanderbilt University School of Medicine , Nashville, Tennessee 2 Centro Nacional de Epidemiología, Instituto de Salud Carlos III , Madrid 3 Hospital Clinic-IDIBAPS, University of Barcelona , Spain 4 Department of Medicine, Autonomous University of Barcelona , Spain 5 Division of Infectious Disease, Department of Medicine, University of Alabama , Birmingham 6 Department of HIV Medicine, Royal Free London NHS Foundation Trust , United Kingdom 7 Center for AIDS Research, University of Washington , Seattle 8 Monforte Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan , Italy 9 Division of Infectious Diseases, University of Calgary , Canada 10 Research Department of Infection and Population Health, University College London Medical School , United Kingdom 11 Veterans Affairs Connecticut Healthcare System , West Haven, Connecticut 12 Department of Infectious Diseases, Copenhagen University Hospital , Denmark 13 Yale University School of Medicine , New Haven 14 Clinical Trials Unit II Infectious Diseases, University of Cologne , Germany 15 School of Social and Community Medicine, University of Bristol , United Kingdom 16 Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne , Switzerland 17 CHU de Bordeaux 18 Bordeaux University , ISPED, INSERM U897 19 Department of Internal Medicine, Division of Infectious Diseases , Center for Infection and Immunity-Amsterdam , Academic Medical Center , The Netherlands 20 Department of Global Health, Academic Medical Center, University of Amsterdam, and Amsterdam Institute of Global Health and Development HIV Monitoring Foundation 21 Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS , Vancouver , Canada 22 Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136) , Paris , France Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. - HIV/AIDS inhibitor has substantially improved the prognosis of human immunodeficiency virus type 1 (HIV-1)–infected patients since its introduction in high-income settings in 1996 [ 1 ]. ART suppresses HIV-1 replication, leading to declines in plasma HIV-1 RNA, increased CD4 T-cell counts, and, eventually, decreased morbidity and mortality [ 2 ]. Because patients have now been treated with ART for up to 20 years, it is of major interest to explore predictors of long-term prognosis. The Antiretroviral Therapy Cohort Collaboration (ART-CC) was initiated in 2000 by investigators from HIV cohort studies in North America and Euro (...truncated)


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Margaret T. May, Jorg-Janne Vehreschild, Adam Trickey, Niels Obel, Peter Reiss, Fabrice Bonnet, Murielle Mary-Krause, Hasina Samji, Matthias Cavassini, Michael John Gill, Leah C. Shepherd, Heidi M. Crane, Antonella d'Arminio Monforte, Greer A. Burkholder, Margaret M. Johnson, Paz Sobrino-Vegas, Pere Domingo, Robert Zangerle, Amy C. Justice, Timothy R. Sterling, José M. Miró, Jonathan A. C. Sterne. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study, Clinical Infectious Diseases, 2016, pp. 1571-1577, 62/12, DOI: 10.1093/cid/ciw183