OBJECTIVE: To assess the impact of immediate vs. deferred antiretroviral therapy (ART) on CD4 recovery among individuals early in HIV infection.
DESIGN: Using serologic markers of early infection together with self-reported dates of infection and HIV diagnosis, ART-naive participants who were randomized to immediate vs. deferred ART in the Strategic Timing of Antiretroviral Treatment trial were classified into subgroups of duration of HIV infection at baseline. CD4 cell count recovery over follow-up according to duration of HIV infection was investigated.
METHODS: Three subgroups were defined: first, infected 6 months or less (n = 373); second, infected 6-24 months (n = 2634); and third, infected 24 months or longer (n = 1605). Follow-up CD4, CD8, and CD4 : CD8 ratio for the immediate and deferred ART groups were compared by subgroup using linear models. For the deferred ART group, decline to CD4 less than 350 cells/μl or AIDS according to infection duration was compared using time-to-event methods.
RESULTS: Follow-up CD4 cell count differences (immediate minus deferred) were greater for those recently infected (+231 cells/μl) compared with the two other subgroups (202 and 171 cells/μl; P < 0.001). CD4 : CD8 ratio treatment differences varied significantly (P < 0.001) according to duration of infection. In the deferred ART group, decline to CD4 less than 350 cells/μl or AIDS was greater among those recently infected (16.1 vs. 13.2 and 10.5 per 100 person years for those infected 6-24 and ≥24 months; P = 0.002).
CONCLUSION: In this randomized comparison of immediate vs. deferred ART, the CD4 cell count difference was greatest for those recently infected with HIV, emphasizing the importance of immediate ART initiation.
Bibliographical noteFunding Information:
The study was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH, grants UM1-AI068641 and UM1-AI120197), National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Additional support was provided by the HIV Prevention Trials Network sponsored by NIAID, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Drug Abuse, National Institute of Mental Health, and the Office of AIDS Research, of the NIH DHHS (UM1 AI068613), and NIAID (R01 AI095068).
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- CD4 recovery
- Strategic Timing of Antiretroviral Treatment
- antiretroviral therapy
- early infection