Early ART initiation up to 2 years after HIV onset protects against viral blips

The initiation of antiretroviral therapy (ART) within 2 years of HIV acquisition is associated with reduced risk for viral blips, indicating reservoir plasticity may extend past the acute disease phase, as well as the possibility of a smaller reservoir size. These study results were published in Clinical Infectious Diseases.

Viral blips are common among individuals with HIV infection on ART and appear to be due to random biological fluctuations.

Researchers sourced data for this analysis from the United States Military HIV Natural History Study, an ongoing study comprising military personnel that began in 1986. The researchers sought to confirm the time period for which early ART initiation reduces the frequency of viral blips in patients with HIV infection. Patients (N=1413) included in the analysis started ART between 1996 and 2022 and were evaluated for viral blips on the basis of time from estimated HIV seroconversion to ART initiation. A viral blip was defined as an HIV RNA level of 401 to 1000 copies/mL.

Among patients included in the final analysis, 96.3% were men, 42.7% were aged between 18 and 29 years at ART initiation, 40.2% started ART at least 2 years after HIV onset, 42.0% were Black, and 45.5% were on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART.

A total of 88 (6.2%) patients experienced viral blips after achieving HIV virologic suppression with ART, of whom 77.3% had a single blip event, 14.8% had 2 blips, 4.5% had 3 blips, and 3.4% had 4 blips. Between 1999 and 2020, the overall blip incidence decreased from 12.5 (95% CI, 7.7-20.4) to 0.6 (95% CI, 0.1-4.4) per 100 person-years.

Compared with those who experienced no viral blips, the subset of patients with viral blips were older at ART initiation (median, 34.9 vs 31.6 years), exhibited a longer time period from HIV acquisition to ART initiation (median, 33.9 vs 16.6 months; P <.0001), had lower rates of NNRTI use (28.4% vs 46.6%; P <.0001), and showed worse ART adherence (P <.0001). Additional between-group analyses indicated patients with blips were more likely to have a history of hepatitis B infection (75.8% vs 53.4%; P <.0001) and CD4⁺ counts at or below 200 cells/mm³ at ART initiation (17.0% vs 9.1%; P £.0307).

In a multivariable analysis, the highest risk for viral blips was associated with the use of unboosted protease inhibitors (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.59-4.03) when compared with the use of NNRTI-based regimens. Patients with a history of hepatitis B infection also exhibited increased risk for viral blips (aHR, 1.22; 95% CI, 1.02-1.46).

The researchers noted shorter time (<24 months) from HIV acquisition to ART initiation was protective against viral blips. Other factors associated with reduced risk for viral blips were as follows:

• Prior hepatitis C infection (aHR, 0.38; 95% CI, 1.02-1.46);
• Integrase strand transfer inhibitor use (aHR, 0.44; 95% CI, 0.28-0.69);
• Consistently high ART adherence (aHR 0.25; 95% CI, 0.20-0.31);
• Black race (aHR, 0.64; 95% CI, 0.53-0.77);
• Hispanic/other race (aHR, 0.48; 95% CI, 0.35-0.67); and,
• Age of 30 to 39 years at ART initiation (aHR, 0.59; 95% CI, 0.44-0.78).

Further analysis was performed after the definition of viral blip was expanded to include HIV RNA levels between 51 and 1000 copies/mL. The researchers noted similar findings, as the risk for viral blips remained lower in patients who initiated ART earlier vs later than 24 months after HIV acquisition.

Limitations of this study include the potential lack of generalizability to more diverse patient populations.

According to the researchers, “[O]ur findings suggest that the window of opportunity to intervene with ART and achieve a beneficial effect in preventing blips may extend to two years after HIV acquisition.”

By Jessica Nye, PhD

References:

Crowell TA, Hsieh H-C, Wang X, et al; for the Infectious Disease Clinical Research Program (IDCRP) HIV Working Group. 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. Clin Infect Dis. Published online March 10, 2025. doi:10.1093/cid/ciaf103