Antiretroviral Therapy within Two Years of HIV Acquisition is Associated with Fewer Viral Blips: A Retrospective Analysis of Over 20 Years of Data from the U.S. Military HIV Natural History Study.

Background: Viral blips have been associated with larger reservoir size and slower decay. Earlier antiretroviral therapy (ART) initiation may decrease the risk of blips.

Methods: We analyzed participants from the U.S. Military HIV Natural History Study with an estimated HIV seroconversion date, viral suppression ≤400 copies/mL within 1 year after starting ART, and at least 3 HIV RNA measurements after suppression. A blip was HIV RNA 401-1000 copies/mL preceded and followed by HIV RNA ≤400 copies/mL without changing ART. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors potentially associated with the time from viral suppression to first blip.

Results: From 1996-2022, 1,413 participants on stable suppressive ART had a median age at HIV diagnosis of 29.2 years (interquartile range 24.9-35.4) and 1361 (96.3%) were males. Viral blips were observed in 88 (6.2%) participants, 68 (77.3%) of whom had a single blip. The overall incidence was 1.2 blips per 100 person-years (95% CI 0.9-1.4). In multivariable modeling, ART initiation within 24 months of estimated HIV acquisition was independently associated with decreased hazard of viral blips as compared to ART initiation after more than 24 months (0-6 months HR 0.29 [95% CI 0.18-0.48]; 6-12 months HR 0.43 [95% CI 0.31-0.59]; 12-24 months HR 0.46 [95% CI 0.35-0.60]).

Conclusions: Participants who initiated ART within two years of HIV acquisition had lower hazard of blips, potentially reflecting smaller reservoir size and suggesting reservoir plasticity that extends beyond the acute phase of HIV.