Sharma, S et al. for the INSIGHT START Study Group. The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection. AIDS. July 1, 2019; 33(8):1335–44.

See also: CROI Seattle | February, 2017. Abstract #472

The Strategic Timing of Antiretroviral Treatment (START) study, randomly assigned 4684 HIV-positive adults with a CD4+ count of >500 cells/µl to begin ART or defer treatment until the CD4+ count decreased to 350 cells/µl. The study was stopped early in 2015 when on the basis of an interim analysis, the DSMB determined that the primary composite end point (any serious AIDS-related event, serious non-AIDS-related event, or death) occurred more often in the delayed treatment group. Prospective data from START participants continues to be collected and analyzed. This component of START evaluated immune recovery based on duration of HIV infection at baseline and CD4+ count at the time of ART initiation. The key outcome was to assess CD4+ cell count recovery after ART was started based on to duration of HIV infection. The authors use serologic markers of early HIV infection together with self-reported dates of infection and HIV diagnosis. They defined three subgroups: those infected 6 months or less (n = 373); those infected 6 to 24 months (n = 2634); and persons infected >24 months (n = 1605). Follow-up CD4+, CD8+, and CD4+/ CD8+ ratios for the immediate versus deferred ART groups were compared by subgroup. For the deferred ART group, decline to CD4+ count to < 350 or AIDS according to infection duration was compared using time-to-event methods. Collectively from START, over an average follow-up of 3 years, mean CD4+ count was 194 cells/µl greater in the immediate versus deferred ART group. However, follow-up CD4+ cell count differences (immediate minus deferred) were greater for those recently infected (+231 cells) compared with the two other subgroups (202 cells and 171 cells; P < 0.001). The CD4+/ CD8+ ratio treatment differences also varied significantly (P < 0.001) according to duration of infection. Of note, in the deferred ART group, decline in CD4+ counts to less than 350 cells/µl was greater among those recently infected (16.1, 13.2, and 10.5 per 100/person years for those infected from 6 to 24 months and ≥24 months; P = 0.002). The authors conclude that in this study of immediate compared to deferred ART, the CD4+ cell count decline was greatest for those recently infected with HIV, emphasizing the importance of early initiation of ART. The overall benefit of early ART from START may actually be understated as more than 90% of participants had been HIV-infected for 6 months or longer.

Author’s Commentary: This study continues to add further evidence of enhanced CD4+ recovery by starting ART as soon as possible after diagnosis. Preserving immune function is one of the key long-term benefits of ART. More data from this cohort will be forthcoming, as the follow-up of START participants is planned to continue through at least 2021.