RESUMO
OBJECTIVES: To evaluate the effects of sex and initial antiretroviral regimen on decay of HIV-RNA and virologic outcome. METHODS: We conducted a viral dynamics substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI) (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals. HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and 8 in A5142 participants. Two-phase viral decay was estimated in the substudy with biexponential mixed-effects modeling and compared using Wilcoxon tests. Week 1 HIV-RNA change was assessed as a predictor of virologic failure (HIV-RNA above 50 or 200â copies/ml) at weeks 24-96 using logistic regression. RESULTS: Sixty-eight individuals were enrolled in the substudy (median HIV-RNA 4.9 log(10) âcopies/ml). Median rates of phase 1 viral decay by treatment were 0.61(EFV/LPV), 0.53(LPV), and 0.63(EFV) per day. Phase 1 decay was significantly faster for EFV than LPV (Pâ=â0.023); other comparisons were not significant (Pâ>â0.11). Viral decay did not differ by sex (Pâ=â0.10). Week 1 HIV-RNA change, calculated in 571 participants of A5142, was greater for the EFV (median -1.47 log(10) âcopies/ml) than either the LPV/EFV or LPV groups (-1.21 and -1.16 log(10â) copies/ml, respectively; Pâ<â0.001). Week 1 HIV-RNA change was associated with virologic failure above 50 âcopies/âml at weeks 24 and 48 (Pâ<â0.018), but not above 200â copies/ml at these time points or for any value at week 96. CONCLUSION: Phase 1 decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV-RNA change predicted virologic outcome up to week 48, but not at week 96.
Assuntos
Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , RNA Viral/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Alcinos , Benzoxazinas/farmacologia , Benzoxazinas/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/metabolismo , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Fatores Sexuais , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection. METHODS: Open-label study in 753 subjects randomized equally to efavirenz or lopinavir/ritonavir(r) plus two nucleoside reverse-transcriptase inhibitor (NRTI) vs. the NRTI-sparing regimen of lopinavir/r plus efavirenz. Zidovudine, stavudine, or tenofovir with lamivudine was selected prior to randomization. Metabolic outcomes through 96 weeks were lipoatrophy, defined as at least 20% loss in extremity fat, and fasting serum lipids. RESULTS: Lipoatrophy by dual-energy X-ray absorptiometry at week 96 occurred in 32% [95% confidence interval (CI) 25-39%] of subjects in the efavirenz plus two NRTIs arm, 17% (95% CI 12-24) in the lopinavir/r plus two NRTIs arm, and 9% (95% CI 5-14) in the NRTI-sparing arm (P < or = 0.023 for all comparisons). Varying the definition of lipoatrophy (> or =10 to > or =40% fat loss) and correction for baseline risk factors did not affect the significant difference in lipoatrophy between the NRTI-containing regimens. Lipoatrophy was most frequent with stavudine-containing regimens and least frequent with tenofovir-containing regimens (P < 0.001), which were not significantly different from the NRTI-sparing regimen. Total cholesterol increases at week 96 were greatest in the NRTI-sparing arm (median +57 mg/dl) compared with the other two arms (+32-33 mg/dl; P < 0.001). Use of lipid-lowering agents was more common (25 vs. 11-13%) in the NRTI-sparing arm. CONCLUSION: Lipoatrophy was more frequent with efavirenz than lopinavir/r when combined with stavudine or zidovudine, and less frequent when either drug was combined with tenofovir. Lipoatrophy was least frequent with the NRTI-sparing regimen, but this benefit was offset by greater cholesterol elevations and the need for lipid-lowering agents.