The benefit of immediate compared with deferred antiretroviral therapy on CD4⁺ cell count recovery in early HIV infection

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.