High rate of long-term clinical events after antiretroviral therapy resumption in HIV-positive patients exposed to antiretroviral therapy interruption

Abstract

Objective: We analyzed the incidence rate of long-term events in patients on antiretroviral therapy (ART) previously exposed to therapy interruption.Design: A single-center cohort study involving participants in ART interruptions (ARTI) clinical trials (n ¼ 10) was conducted.Methods: Non-AIDS events after ART resumption were analyzed. A control group not exposed to ARTI was randomly selected from the same cohort and a propensity score of belonging to ARTI group was estimated based on age, sex, CD4 þ nadir value, time from HIV diagnosis to ARTI, time from HIV diagnosis to starting ART and time of suppressed viral load, and used to adjust effect estimates.Results: One hundred and eighty-one patients were included, 136 in ARTI and 45 in the control arm. Median time of known HIV-1 infection was 21 years and median time from ART resumption to first non-AIDS event was 5.2 years. A significantly higher proportion of patients with ARTI had an event as compared with control group [raw percentages: 43% (n ¼ 53) vs. 23% (n ¼ 10), P ¼ 0.015]. These differences were confirmed when only the non-AIDS events occurring after ART resumption were analyzed [adjusted hazard ratio (aHR) ¼ 2.43, 95% confidence interval (CI) 1.15-5.12]. The logistic model adjusted for the propensity score indicated that patients with an ARTI had a four-fold higher risk of having at least one non-AIDS event (P ¼ 0.002). Conclusion:We found a higher risk of having at least one non-AIDS event years after ART resumption in HIV-infected patients exposed to ARTI as compared with controls. These data should be taken into consideration for future functional cure clinical trials.

Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021

“…This should include the development of home-based tests that may not necessarily require high sensitivity as long as testing is performed frequently 55 . Finally, emerging evidence suggests that virus replication during an ATI may be associated with some long-term adverse events 56 , so careful follow up of participants in ATI studies will be necessary.…”

Analytical treatment interruption: detection of an increase in the latent, inducible HIV-1 reservoir more than a decade after viral resuppression

“…Although raising several debatable ethical concerns [2][3][4] , analytical treatment interruption (ATI) studies are increasingly being used to assess the efficacy of novel therapeutic strategies designed to target the viral reservoir and/or control HIV-1 in absence of ART [5][6][7] . Findings from past and recent studies indicate that HIV-1 viremia during ATI may be associated with long-term adverse clinical events, clearly warranting vigilant follow-up of ATI study participants [8][9][10] . One particular area of concern is the heightened risk of HIV-1 reservoir reseeding during ATI.…”