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

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 = 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+ 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 = 53) vs. 23% (n = 10), P = 0.015]. These differences were confirmed when only the non-AIDS events occurring after ART resumption were analyzed [adjusted hazard ratio (aHR) = 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 = 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.

Antiretroviral Therapy Interruption (ATI) in HIV-1 Infected Patients Participating in Therapeutic Vaccine Trials: Surrogate Markers of Virological Response.

A functional Human immunodeficiency Virus (HIV) cure has been proposed as an alternative to antiretroviral treatment for life, and therapeutic vaccines represent one of the most promising approaches. The goal of therapeutic vaccination is to augment virus-specific immune responses that have an impact on HIV viral load dynamics. To date, the agreed feature to evaluate the effects of these therapeutic interventions is analytical antiretroviral treatment interruption (ATI), at least until we find a reliable biomarker that can predict viral control. Different host, immunologic, and virologic markers have been proposed as predictors of viral control during ATI after therapeutic interventions. This review describes the relevance of ATI and the different surrogate markers of virological control assessed in HIV therapeutic vaccine clinical trials.