Background:  Therapy in early HIV infection followed by treatment interruption may enhance viral control and allow deferral of chronic therapy. We hypothesized that individuals treated during acute HIV-1 infection (usual estimated infection in prior 14 days) would have better viral control than those treated during recent HIV-1 infection (usual estimated infection in prior 14 to 180 days) 24 weeks after treatment interruption.

Methods:  Subjects entered a phase II multicenter prospective non-randomized trial of ritonavir-boosted protease inhibitor-based antiretroviral therapy stratified by acute infection vs recent infection with predefined criteria. If subjects sustained ≥52 weeks of viral suppression <50 copies/mL, treatment was interrupted. If rebound viremia occurred (> 5000 copies/mL on 3 consecutive visits or >50,000 copies/mL on 2 visits), a second treatment course was initiated and, if successful in suppressing viremia was again followed by treatment interruption. The primary study endpoint was maintaining a plasma viral load <5000 copies/mL for 24 weeks following first or second treatment interruption.

Results:  Between July 1999 and September 2003, 121 subjects were enrolled at 15 AIDS Clinical Trials Group (ACTG) sites. Of the 121 enrolled subjects, 115 were men, the median age was 34 years; 84 were white, and 114 had no history of injection drug use. Median CD4⁺ T cell count at baseline was 535 (25^th to 75^th percentile, 422 to 753) cells/mm³ and median baseline viral load was higher in the AI (210,000 copies/mL) than in the recently infected (43,000 copies/mL) group. Baseline resistance mutations were approximately 15% in each group. The 73 subjects (28 acute infections, 45 recent infections) who entered the first treatment interruption form the primary endpoint analysis population. The primary endpoint of sustained virologic suppression <5000 copies/mL was achieved in 29 (40%) of the 73. There was no significant difference (p = 0.81) in virologic success between those with acute infections (43%, 95%CI 24 to 63%) and those with recent infections (38%, 95%CI 24 to 53%). Successful outcomes were more common in the combined trial population with baseline viral load <100,000/mL 22 of 46 (48%) than in those with >100,000/mL, 7 of 27 (26%). Treatment was in general well tolerated.

Conclusions:  Of subjects treated during acute or recent infection, 40%sustained a viral load <5000 copies/mL after 24 weeks of treatment interruption. There was no significant difference between the 2 groups. Even earlier intervention may be required to improve outcome of primary HIV infection.