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. 2025 Apr 15;231(4):e792-e802.
doi: 10.1093/infdis/jiaf117.

Impact of Switching to Long-Acting Injectable Cabotegravir Plus Rilpivirine on Rectal HIV-1 RNA Shedding and Implications for Transmission Risk

Mar Masiá  1   2   3   4 , Marta Fernández-González  1   3   4 , Christian Ledesma  1   4 , Maria Losada-Echeberría  5 , Nieves Gonzalo-Jiménez  3   6 , Paula Mascarell  1   2   3 , Javier García-Abellán  1   2   3   4 , Leandro López  1   3   4 , Melissa Bello-Pérez  1   4 , Sergio Padilla  1   2   3   4 , Felix Gutiérrez  1   2   3   4
Affiliations

Impact of Switching to Long-Acting Injectable Cabotegravir Plus Rilpivirine on Rectal HIV-1 RNA Shedding and Implications for Transmission Risk

Mar Masiá et al. J Infect Dis. .

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.

Keywords: HIV transmission risk; cabotegravir; pharmacokinetic; rectal shedding; rilpivirine.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
HIV-1 RNA levels in plasma and rectal secretions by study visit: (A) HIV-1 RNA levels in plasma; and (B) HIV-1 RNA levels in rectum. Baseline, at day of first intramuscular injection; and at 1, 3, 5, 7, and 9 months after the first intramuscular injection. The dashed lines represent the limit of detection of HIV-1 RNA < 50 (1.69 log10) copies/mL in plasma and <50 copies/swab in rectum. Limit values of viral load considered of low/lower risk of transmission are also represented in both compartments: 200 (2.30 log10) copies/mL (A) and copies/swab (B) and 1000 (3 log10) copies/mL (A) and copies/swab (B).
Figure 2.
Figure 2.
Rectal rilpivirine trough concentrations according to rectal HIV-1 RNA levels. The circles represent individual data observations. The lines and bars form a boxplot displaying the data distribution, including the median, first, and third quartiles. The whiskers extend up to 1.5 times the IQR. The shaded area represents a density distribution plot.
See this image and copyright information in PMC

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