Antiretroviral Therapy Within 2 Years of HIV Acquisition Is Associated With Fewer Viral Blips: A Retrospective Analysis of More Than 20 Years of Data From the US Military HIV Natural History Study

Abstract

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 US Military HIV Natural History Study with an estimated human immunodeficiency virus (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 defined as 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 through 2022, among 1413 participants on stable suppressive ART, 88 (6.2%) had at least one blip, including 68 (77.3%) with only a single blip. The overall incidence was 1.2 blips per 100 person-years (95% CI: .9-1.4). In multivariable modeling, ART initiation within 24 months of estimated HIV acquisition was independently associated with decreased hazard of viral blips compared with ART initiation after more than 24 months (0-6 months HR: 0.29 and 95% CI: .18-.48; 6-12 months HR: 0.43 and 95% CI: .31-.59; 12-24 months HR: 0.46 and 95% CI: .35-.60).

Conclusions: Participants who initiated ART within 2 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.

Keywords: acquired immunodeficiency syndrome; anti-HIV agents; antiretroviral agents; reservoir; viremia.

Graphical Abstract

Figure 1.

Annual trends in viral load testing and viral blip incidence. A, The number of viral load tests performed (red/right bars), number of participant visits completed (blue/left bars), and average testing rate calculated from these numbers (tests per visit, green line) for calendar years 1997–2022. B, The incidence of blips during these same calendar years, calculated as number of blips per 100 person-years of observation time. The following years have the same incidence rate (IR): 2003, 2005, and 2017 (IR = 0.5 per 100 person-years), 2007 and 2012 (IR = 0.4 per 100 person-years), 2008 and 2010 (IR = 1.2 per 100 person-years), and 2016 and 2018 (IR = 0.2 per 100 person-years).

Figure 2.

Kaplan–Meier survival curves for factors associated with time to first viral blip. Kaplan–Meier curves were generated to visually explore factors that were identified as having significant associations with time to first HIV RNA 401–1000 copies/mL in the multivariable model. These included (A) time from estimated HIV aquisition to ART initiation; (B) age; (C) sex; (D) race; (E) ART regimen; (F) ART adherence; (G) history of hepatitis B; and (H) history of hepatitis C. Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; INSTI, integrase strand transferase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.