Virologically suppressed individuals with historical rilpivirine resistance-associated mutations maintained suppression after switching to long-acting CAB/

The impact of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) on rectal HIV-1 RNA dynamics and the factors associated with viral shedding remain poorly understood.MethodsThis prospective study evaluated HIV-1 RNA dynamics by analyzing sequential paired plasma and rectal fluid samples from virologically-suppressed individuals who transitioned from oral antiretroviral therapy (ART) to every-two-month CAB/RPV (preceded or not by oral lead-in), over a 9-month follow-up period. RPV trough concentrations were measured in 384 rectal samples.Results597 plasma and 561 rectal samples from 90 participants were analyzed. HIV-1 RNA >50 (>1.69 log10) copies/swab was detected in 14.7% (59/401) of rectal samples (42.2% of participants) during intramuscular CAB/RPV, and in 17.5% (28/160) of rectal samples (29% of participants) during oral ART. Median (range) detectable rectal HIV-1 RNA level during intramuscular ART was 362 (226-659) copies/swab. The frequency and quantity of rectal shedding did not differ between groups with/without oral lead-in. No correlation was observed between rectal shedding and detectable plasma HIV-1 RNA. Median (Q1-Q3) rectal RPV concentration was 3.07 (2.83-3.35) log10 ng/swab, 1.6-fold above the EC90 for rectal tissue, and did not correlate with rectal HIV-1 RNA levels. Rectal shedding was associated with plasma pre-ART HIV-1 RNA >5 log10 in multivariate Cox regression, but was unrelated to established predictors of virological failure with CAB/RPV.ConclusionRectal HIV-1 shedding is common during bimonthly intramuscular CAB/RPV treatment and is also observed with oral ART. Shedding was independent of concurrent plasma HIV-1 RNA and rectal RPV concentrations, and was associated with pre-ART viral load.

This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK).MethodsA prospective cohort study was conducted on people with human immunodeficiency virus (HIV, PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB + RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma human immunodeficiency virus type 1 (HIV-1) viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes.ResultsAmong 173 patients with a median (interquartile range [IQR]) follow-up of 11.1(7.1–13.2) months and 789 pre-dose measurements, 38.7% experienced VL ≥ 20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in 2 cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis (adjusted hazard ratio [AHR]: 1.49 per log10 VL, 95% confidence interval [CI]: 1.04–2.12, P = .027), detectable viremia on oral ART (AHR: 2.45, 95% CI: 1.29–4.65, P = .006), and the level of viral suppression at transition (AHR: 0.38, 95% CI: .19–.75, P = .004). We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models.ConclusionsNon-sustained viral suppression in PWH transitioning from stable oral ART to CAB + RPV LA was linked to preexisting factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.