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Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine.
Chawki, Sylvain; Goldwirt, Lauriane; Mouhebb, Mayssam El; Gabassi, Audrey; Taouk, Milad; Bichard, Iris; Loze, Bénédicte; Amara, Ali; Brand, Rhonda; Siegel, Aaron; McGowan, Ian; Costagliola, Dominique; Assoumou, Lambert; Molina, Jean-Michel; Delaugerre, Constance.
Afiliação
  • Chawki S; Université de Paris Cité, INSERM U-944, Institut Recherche Saint Louis.
  • Goldwirt L; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Service de Maladies Infectieuses.
  • Mouhebb ME; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Laboratoire de Pharmacologie Biologique.
  • Gabassi A; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique.
  • Taouk M; Université de Paris Cité, INSERM U-944, Institut Recherche Saint Louis.
  • Bichard I; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Service de Virologie.
  • Loze B; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Service de Gastro-entérologie, Paris, France.
  • Amara A; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Service de Maladies Infectieuses.
  • Brand R; Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Saint Louis, Service de Maladies Infectieuses.
  • Siegel A; Université de Paris Cité, INSERM U-944, Institut Recherche Saint Louis.
  • McGowan I; University of Pittsburgh, Magee-Women's Research Institute and Foundation, Pittsburgh, Pennsylvania, USA.
  • Costagliola D; University of Pittsburgh, Magee-Women's Research Institute and Foundation, Pittsburgh, Pennsylvania, USA.
  • Assoumou L; University of Pittsburgh, Magee-Women's Research Institute and Foundation, Pittsburgh, Pennsylvania, USA.
  • Molina JM; Orion Biotechnology, Ottawa, Ontario, Canada.
  • Delaugerre C; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique.
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, 2 h 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 -144 pg/ml/mg (IQR[-259;-108]) for the 2 h-double dose group ( P  = 0.0005) and -179 pg/ml/mg (IQR [-253;-86]) for the 7 days-single dose group ( P  = 0.001), with no differences between groups ( P  = 0.93). 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  = -0.84; P  = 0.0001). CONCLUSION: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 h after a double dose or 7 days of a daily dose. At 2 h, 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Soropositividade para HIV / Fármacos Anti-HIV / Profilaxia Pré-Exposição Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Soropositividade para HIV / Fármacos Anti-HIV / Profilaxia Pré-Exposição Idioma: En Ano de publicação: 2024 Tipo de documento: Article