RESUMO
OBJECTIVES: Distal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre-existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV-infected Thai individuals naïve to ARV therapy. METHODS: Distal leg and proximal thigh ENFDs were quantified in HIV-infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8-oxo-deoxyguanine (8-oxo-dG) break frequencies. RESULTS: In 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2-26.6) for the distal leg and 31.7 (26.2-40.0) for the proximal thigh. By linear regression, lower CD4 count (P < 0.01), older age (P < 0.01), increased body mass index (BMI) (P = 0.04), increased height (P = 0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P = 0.02) were associated with lower distal leg ENFD. CONCLUSIONS: Older age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV-infected subjects free of neuropathy prior to initiation of first-time ARV therapy.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Soropositividade para HIV/fisiopatologia , Síndromes Neurotóxicas/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Polineuropatias/fisiopatologia , Adulto , Distribuição por Idade , Fármacos Anti-HIV/administração & dosagem , Índice de Massa Corporal , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Fibras Nervosas/patologia , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Polineuropatias/epidemiologia , Polineuropatias/etiologia , Valor Preditivo dos Testes , Estavudina/efeitos adversos , Tailândia/epidemiologiaRESUMO
OBJECTIVES: The aim of the study was to determine the incidence of, and risk factors for, nevirapine (NVP)-associated hepatotoxicity and rash in HIV-infected Thai men and women, including pregnant women, receiving NVP-containing highly active antiretroviral therapy (HAART). METHODS: NVP-containing HAART was prescribed to eligible men and women enrolled in the Prevention of Mother-To-Child Transmission of HIV (PMTCT) and MTCT-Plus programmes. All pregnant women received zidovudine (ZDV)/lamivudine (3TC)/NVP from >14 weeks of gestational age if their CD4 cell count was