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1.
J Antimicrob Chemother ; 78(2): 497-503, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36512383

RESUMO

BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/uso terapêutico , Homossexualidade Masculina , Integrases , Piridonas/uso terapêutico , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
2.
Infect Control Hosp Epidemiol ; 24(10): 724-30, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14587931

RESUMO

OBJECTIVE: To assess the prevalence of HIV antiretroviral resistance among source patients for occupational HIV exposures. DESIGN: Blood and data (eg, stage of HIV, previous antiretroviral drug therapy, and HIV RNA viral load) were collected from HIV-infected patients who were source patients for occupational exposures. SETTING: Seven tertiary-care medical centers in five U.S. cities (San Diego, California; Miami, Florida; Boston, Massachusetts; Albany, New York; and New York, New York [three sites]) during 1998 to 1999. PARTICIPANTS: Sixty-four HIV-infected patients who were source patients for occupational exposures. RESULTS: Virus from 50 patients was sequenced; virus from 14 patients with an undetectable (ie, < 400 RNA copies/mL) viral load could not be sequenced. Overall, 19 (38%) of the 50 patients had primary genotypic mutations associated with resistance to reverse transcriptase or protease inhibitors. Eighteen of the 19 viruses with primary mutations and 13 wild type viruses were phenotyped by recombinant assays; 19 had phenotypic resistance to at least one antiretroviral agent. Of the 50 source patients studied, 26 had taken antiretroviral agents in the 3 months before the occupational exposure incident. Sixteen (62%) of the 26 drug-treated patients had virus that was phenotypically resistant to at least one drug. Four (17%) of 23 untreated patients had phenotypically resistant virus. No episodes of HIV transmission were observed among the exposed HCWs. CONCLUSIONS: There was a high prevalence of drug-resistant HIV among source patients for occupational HIV exposures. Healthcare providers should use the drug treatment information of source patients when making decisions about post-exposure prophylaxis.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Pessoal de Saúde , Exposição Ocupacional/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Genótipo , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Exposição Ocupacional/análise , Fenótipo , Prevalência , Estados Unidos
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