Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine.
AIDS
; 38(4): 455-464, 2024 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-37976073
OBJECTIVES: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as preexposure prophylaxis (PrEP), using ex-vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. DESIGN/METHODS: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex-vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, 2âh after two pills or 7 days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. RESULTS: Twelve and 11 men were analyzed in the 2 h-double dose and 7 days-single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144âpg/ml/mg (IQR[-259;-108]) for the 2 h-double dose group ( P â=â0.0005) and -179âpg/ml/mg (IQR [-253;-86]) for the 7 days-single dose group ( P â=â0.001), with no differences between groups ( P â=â0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at 7 days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose ( R â=â-0.84; P â=â0.0001). CONCLUSION: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2âh after a double dose or 7âdays of a daily dose. At 2âh, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
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HIV-1
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Soropositividade para HIV
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Fármacos Anti-HIV
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Profilaxia Pré-Exposição
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article