Multidisciplinary assessment of the HIV-1 reservoir following switch from 3-drug to 2-drug antiretroviral regimens in virologically suppressed patients over an 18 months follow-up period. An observational, prospective pilot study

In people living with HIV-1 (PLWH), two-drug antiretroviral therapy (2DR-ART) regimens are increasingly being used with comparable efficacy and reduced drug toxicity compared to 3DR-ART. The aim of this project was to assess, in an observational, prospective pilot study, whether switching virologically suppressed PLWH from 3DR-ART to 2DR-ART has an impact on their HIV latent reservoir. PLWH who continued a 3DR-ART and PLWH that switched to 2DR-ART were investigated at enrolment (T0) and 18 months later (T1) for cell-associated HIV-RNA (CAR), HIV-DNA (CAD) and HIV intact proviruses (IP) in CD4+ T-cells. CAR was quantified using a digital PCR (dPCR) assay targeting LTR. CAD and IP were quantified by a triplex dPCR targeting LTR for CAD and psi and ENV regions of the HIV-1 genome for IP. All the assays were performed on a QIAcuity platform. Multivariate linear regression analysis was performed to identify predictors of CAR, CAD and IP changes over time (T1-T0). At baseline, there were no significant differences between 2DR and 3DR groups for CAD, CAR and IP. Among the three HIV-1 molecular parameters, there was a significant correlation between CAD(T0) and CAR(T0). No significant changes over time (T1 - T0) were observed for any of the three reservoir indicators, both in the overall population and within or between the 2DR and 3DR groups. In a regression model including treatment group, age, nadir and baseline CD4+ cell counts, zenith viral load, ART duration, and baseline CAD, CAR and IP values we found that higher baseline CD4+ counts was positively associated with changes of CAD, while zenith viral load and CAD(T0) were negatively associated with changes of IP. CAD and CAR were correlated with each other but not with IP at T0. CAD, IP and CAR values were stable over 18 months irrespective of treatment, reassuring that switching to 2DR does not affect the size of the viral reservoir in the medium term. Higher CAD values seem to predict larger decreases in the IP proportion, but prolonged follow-up is needed to establish the clinical utility of testing for molecular markers of the HIV reservoir before treatment simplification in PLWH.