Abstract
BACKGROUND: The impact of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) on rectal human immunodeficiency virus 1 (HIV-1) RNA dynamics and the factors associated with viral shedding remain poorly understood. METHODS: This 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-2-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. RESULTS: In total, 597 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 detectable rectal HIV-1 RNA level during intramuscular ART was 362 (range, 133-2216) 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 rectal RPV concentration was 3.07 (quartile 1-quartile 3, 2.83-3.35) log10 ng/swab, 1.6-fold above the 90% maximum effective concentration (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. CONCLUSIONS: Rectal 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.