RESUMO
BACKGROUND: Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF. METHODS: A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50â copies/mL or one VL of ≥200â copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms. RESULTS: Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive. CONCLUSIONS: This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.
Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Piridonas , Triazóis , Carga Viral , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Piridonas/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , França , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Triazóis/uso terapêutico , Genótipo , Mutação , Transcriptase Reversa do HIV/genética , Terapia Antirretroviral de Alta Atividade , Resultado do TratamentoRESUMO
Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.
Assuntos
Coinfecção , Infecções por HIV , Anticorpos Anti-Hepatite , Hepatite D , Vírus Delta da Hepatite , Carga Viral , Humanos , Mauritânia/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Masculino , Adulto , Feminino , Prevalência , Vírus Delta da Hepatite/genética , Anticorpos Anti-Hepatite/sangue , Coinfecção/epidemiologia , Coinfecção/virologia , Hepatite D/epidemiologia , Hepatite D/complicações , Pessoa de Meia-Idade , Prognóstico , Hepatite B/epidemiologia , Hepatite B/complicações , Hepatite B/virologia , Genótipo , Adulto Jovem , Vírus da Hepatite B/genéticaRESUMO
In 2022, the World Health Organization (WHO) estimated that hepatitis B virus (HBV) infections caused 1.5 million deaths, mostly attributable to complications from chronic infections, cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of a vaccine, 296 million people were chronically infected in 2019. Asia and Africa are the continents most affected by this infection, with around 100 million people infected in Africa as a whole.Hepatitis Delta or D virus (HDV), which is a "satellite" virus of HBV, is often misunderstood and its diagnosis remains neglected. However, it is associated with acute fulminant forms and chronic forms of hepatitis leading to a more rapid evolution towards cirrhosis and HCC than during HBV mono-infection. Research on these two viruses HBV and HDV has progressed a lot in recent years, and new treatments are currently in development.In people living with the human immunodeficiency virus (PlHIV), liver disease is a major cause of morbidity and mortality. Due to common modes of transmission, dual or triple HIV/HBV or HIV/HBV/HDV infections are relatively common, particularly in HBV endemic regions such as Africa. However, while today most co-infected patients benefit from effective treatment against both HIV and HBV, the latter is not active against HDV. In Africa, hepatitis B and D have already been the subject of several studies. However, the frequency and clinical consequences of these co-infections have been little studied in the general population and in PlHIV.This review seeks to update the epidemiological and clinical data and the therapeutic perspectives of HDV co-infections or triple infections (HIV-HBV-HDV) in Africa.