The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals

Abstract

Background: The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved.

Methods: A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group).

Results: At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings.

Conclusions: Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment.

Clinical trials registration: NCT00090779.

Figure 1.

Time to meeting eligibility criteria for initiation or reinitiation of antiretroviral therapy (ART) for the immediate treatment (IT) and deferred treatment (DT) groups over the 96 weeks of the study; times were significantly longer in the IT group (P < .001; log–rank test).

Figure 2.

Time to meeting eligibility criteria for initiation or reinitiation of antiretroviral therapy (ART) for the immediate treatment (IT) and deferred treatment (DT) groups. The time origin for the IT group was the time when ART was interrupted (week 36), and the time origin for the DT group was week 0. The curves remain significantly different (P = .035 by log–rank test), but the analysis includes only those in the IT group who continued ART through week 36 (n = 49), compared with all in the DT group (n = 64), and therefore it is not a truly randomized comparison.