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1.
J Neurovirol ; 21(5): 525-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26002840

RESUMO

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.


Assuntos
Antirretrovirais/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia , Células Receptoras Sensoriais/patologia , Adulto , Estudos Transversais , Feminino , Humanos , Perna (Membro) , Masculino , Fatores de Risco , Pele/inervação , Estavudina/efeitos adversos , Tenofovir/efeitos adversos , Tailândia , Zidovudina/efeitos adversos
2.
Antivir Ther ; 17(8): 1521-31, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23220732

RESUMO

BACKGROUND: Due to superior long-term toxicity profiles, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF) are preferred over stavudine (d4T) for first-line antiretroviral regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anaemia. METHODS: We randomized (1:1:1) 150 treatment-naive Thai HIV-infected adults with CD4(+) T-cell count <350 cells/mm(3) to arm 1 (24-week GPO-VIR S30(®) [d4T plus lamivudine (3TC) plus nevirapine (NVP)] followed by 48-week GPO-VIR Z250(®) [AZT plus 3TC plus NVP]), arm 2 (72-week GPO-VIR Z250(®)) or arm 3 (72-week TDF plus emtricitabine [FTC] plus NVP). Haemoglobin (Hb), dual energy x-ray absorptiometry, neuropathic signs, estimated glomerular filtration rate (eGFR), CD4(+) T-cell count, plasma HIV RNA and adherence were assessed. RESULTS: In an intention-to-treat analysis, mean Hb decreased from baseline to week 24 in arm 2 compared with arm 1 (-0.19 versus 0.68 g/dl; P=0.001) and arm 3 (0.48 g/dl; P=0.010). Neuropathic signs were more common in arm 2 compared with arm 3 (20.4 versus 4.2%; P=0.028) at week 24. There were no differences in changes in peripheral fat and eGFR from baseline to weeks 24 and 72 among arms. CD4(+) T-cell count increased more in arm 1 than arms 2 and 3 from baseline to week 24 (168 versus 117 and 118 cells/mm(3); P=0.01 and 0.02, respectively) but the increase from baseline to week 72 was similar among arms. CONCLUSIONS: A 24-week d4T lead-in therapy caused less anaemia and greater initial CD4(+) T-cell count increase than initiating treatment with AZT. This strategy could be considered in patients with baseline anaemia or low CD4(+) T-cell count. If confirmed in a larger study, this may guide global recommendations on antiretroviral initiation where AZT is more commonly used than TDF.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adenina/administração & dosagem , Adenina/análogos & derivados , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Contagem de Linfócito CD4 , Dieta , Esquema de Medicação , Substituição de Medicamentos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/virologia , Hemoglobinas/metabolismo , Humanos , Lamivudina/administração & dosagem , Masculino , Nevirapina/administração & dosagem , Organofosfonatos/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estavudina/administração & dosagem , Tenofovir , Resultado do Tratamento , Carga Viral , Zidovudina/administração & dosagem
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