Effectiveness of second-generation integrase strand-transfer inhibitor-based regimens for antiretroviral-experienced people with HIV who had viral rebound

Abstract

Background: Antiretroviral regimens containing a second-generation integrase strand-transfer inhibitor (INSTI) plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) are the recommended therapy for people with HIV (PWH) who are antiretroviral-naïve or on stable antiretroviral therapy (ART) with viral suppression. Real-world data on the virologic effectiveness of co-formulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among PWH with virologic failure while receiving other ART remain sparse.

Methods: We retrospectively reviewed the medical records of PWH who had viral rebound with plasma HIV RNA >1000 copies/mL and were switched to either dolutegravir combined with 2 NRTIs or BIC/FTC/TAF. The primary end point was re-achieving viral suppression within the first 48 weeks of switch. The association between NRTI-related resistance-associated mutations (RAMs) and virologic effectiveness was examined.

Results: Seventy-nine PWH with viral rebound while receiving other antiretroviral regimens were included. Within the first 48 weeks of switch, the overall probability of re-achieving viral suppression was 79.7% (82.5% [33/40] and 76.9% [30/39] for BIC/FTC/TAF and dolutegravir-based regimens, respectively, p = 0.78). PWH with a higher CD4 lymphocyte count (adjusted odds ratio, per 100-cell/mm³ increase, 1.41; 95% confidence interval, 1.02-1.95) were more likely to re-achieve viral suppression. Among PWH switching to BIC/FTC/TAF who had pre-existing RAMs to NRTIs before switch, 14 of 15 (93.3%) successfully achieved viral suppression.

Conclusions: Switching to BIC/FTC/TAF and dolutegravir-based regimens could re-achieve viral suppression in four-fifth of the PWH who experienced viral rebound during treatment with other antiretroviral regimens. Pre-existing NRTI-related RAMs did not have adverse impact on the effectiveness of dolutegravir combined with 2 NRTIs or BIC/FTC/TAF.

Keywords: Bictegravir; Dolutegravir; Genetic barrier; Nucleoside reverse-transcriptase inhibitor; Resistance-associated mutation; Salvage therapy; Virologic failure.