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1.
Clin Infect Dis ; 79(1): 189-195, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38207125

RESUMO

BACKGROUND: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. METHODS: We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. RESULTS: Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. CONCLUSIONS: This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.


Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Piridonas , Rilpivirina , Falha de Tratamento , Humanos , Rilpivirina/uso terapêutico , Rilpivirina/farmacocinética , Rilpivirina/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Piridonas/farmacocinética , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Masculino , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , HIV-1/efeitos dos fármacos , HIV-1/genética , Pessoa de Meia-Idade , Adulto , Feminino , Países Baixos , Carga Viral/efeitos dos fármacos , Genótipo , Dicetopiperazinas
2.
Antivir Ther ; 22(8): 727-729, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28367828

RESUMO

The authors report the difficulties of preventing mother-to-child transmission in a pregnant HIV-infected woman with a phobia of swallowing pills. After multiple attempts and just as many failures, the authors ended up with cART consisting of small tablets of nevirapine, lamivudine and a continuous intravenous infusion of zidovudine given via an elastomeric pump at home. This case demonstrates the difficulties that HIV physicians can encounter in pregnant women who have difficulties in swallowing tablets. In exceptional circumstances, continuous infusion of zidovudine may be an option, even in an outpatient setting.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Transtornos Fóbicos/complicações , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/administração & dosagem , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/virologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/virologia , Resultado do Tratamento
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