RESUMO
OBJECTIVE: Evaluate the impact of switching from twice-daily zidovudine/lamivudine (AZT/3TC) to once-daily tenofovir DF plus emtricitabine (TDF/FTC) with efavirenz (EFV). DESIGN: Prospective, multicenter, single-arm 24-week trial. METHODS: Patients on EFV + AZT/3TC for > or =8 weeks with HIV-1 RNA <400 copies/mL were switched to EFV + TDF/FTC and assessed for safety/tolerability, virologic and immunologic responses, adherence, and quality of life at 4, 12, and 24 weeks. RESULTS: Of 402 patients, 2% discontinued for an adverse event (AE) and 1 patient for virologic failure. At 24 weeks, 87% had HIV RNA <400 copies/mL, and 74% versus 71% at baseline had undetectable (HIV RNA <50 copies/mL) viral load (ITT; M=F). Treatment-emergent AEs were infrequent (< or = 5%) with gastrointestinal complaints being the most common. At 24 weeks compared to baseline, hemoglobin (Hb) increased by a median of 0.6 g/dL (p < .001), and a decrease in creatinine clearance of 7.6 mL/min (p < .001) was observed. Fasting lipids decreased slightly (p < .02) in a subset of patients studied (n = 160). A higher percentage of patients reported being "very satisfied" with treatment and the absence of regimen side effects at 24 weeks versus baseline (p < .001). At 24 weeks, 86% of patients took > or = 95% of doses versus 78% at baseline (p = .002). CONCLUSION: Patients switched to EFV + TDF/FTC maintained virologic suppression and the regimen was well tolerated. Patients reported increased satisfaction with treatment and fewer were bothered by side effects.
Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Organofosfonatos/administração & dosagem , Zidovudina/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Idoso , Antirretrovirais/efeitos adversos , Creatinina/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Emtricitabina , Feminino , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Hemoglobinas/análise , Humanos , Lamivudina/efeitos adversos , Lipídeos/sangue , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Cooperação do Paciente , Satisfação do Paciente , Qualidade de Vida , RNA Viral/sangue , Tenofovir , Resultado do Tratamento , Carga Viral , Zidovudina/efeitos adversosRESUMO
A randomized, open-label, multicenter study was conducted to evaluate the therapeutic switch to a single-tablet formulation of efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) among virologically suppressed, HIV-1-infected subjects. Eligible subjects on stable antiretroviral therapy (ART) with HIV-1 RNA less than 200 copies per milliliter for 3 months or more were stratified by prior protease inhibitor (PI)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy and randomized (2:1) to EFV/FTC/TDF or to stay on their baseline regimen (SBR). Patient-reported measures were quality of life (QOL; SF-36 [version 2]), treatment adherence (visual analogue scale), preference of medication (POM), perceived ease of the regimen for condition (PERC), and a 20-item HIV symptom index. Overall, 203 subjects were randomized to EFV/FTC/TDF and 97 to SBR. Fifty-three percent of subjects had previously received a PI-based regimen; 47% an NNRTI-based therapy. Throughout the study, SF-36 summary scores did not differ significantly from baseline, regardless of previous ART or treatment allocation. Adherence was 96% or more in both groups at baseline and all subsequent study visits. At study conclusion, the EFV/FTC/TDF regimen was considered easier to follow than prior regimens by 97% and 96% of subjects previously receiving PI-based and NNRTI-based therapies, respectively. Overall, 91% of subjects switched to EFV/FTC/TDF indicated a preference over their prior therapy. Switching to EFV/FTC/TDF was associated with transient worsening/emergence of dizziness and sustained improvements in several other HIV-related symptoms. In conclusion, switching virologically suppressed, HIV-1-infected subjects from PI-based or NNRTI-based regimens to EFV/FTC/TDF was associated with maintained QOL and treatment adherence, and improved ease of use and treatment satisfaction.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV , Benzoxazinas , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Organofosfonatos , Inibidores da Transcriptase Reversa , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Ciclopropanos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Emtricitabina , Feminino , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Cooperação do Paciente , Preferência do Paciente , Porto Rico , Qualidade de Vida , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Índice de Gravidade de Doença , Comprimidos/administração & dosagem , Comprimidos/uso terapêutico , Tenofovir , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: To evaluate a simplification strategy for HIV-1-infected patients virologically suppressed on antiretroviral therapy (ART) by switching to a single-tablet regimen consisting of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). DESIGN: : Prospective, randomized, controlled, open-label, multicenter study. METHODS: Patients on stable ART with HIV-1 RNA <200 copies per milliliter for > or = 3 months were stratified by prior nonnucleoside reverse transcriptase inhibitor-based or protease inhibitor-based therapy and randomized (2:1) to simplify treatment to EFV/FTC/TDF or to stay on their baseline regimen (SBR). Efficacy and safety assessments were performed at baseline and at weeks 4, 12, 24, 36, and 48. Additional patient-reported outcomes included the following: adherence by visual analog scale, quality of life by SF-36 (v2) survey, HIV Symptom Index, and the Preference of Medication and Perceived Ease of the Regimen for Condition questionnaires. RESULTS: Three hundred patients (EFV/FTC/TDF 203, SBR 97) were evaluated (prior protease inhibitor-based ART, 53%; nonnucleoside reverse transcriptase inhibitor-based ART, 47%). The arms were well balanced at baseline with 88% males, 29% blacks, and a mean age of 43 years; CD4 was 540 cells per cubic millimeter, 96% had HIV-1 RNA <50 copies per milliliter, and 88% were on their first ART regimen. Through 48 weeks, 89% vs. 88% in the EFV/FTC/TDF vs. SBR arms, respectively, maintained HIV-1 RNA <200 copies per milliliter by time to loss of virologic response algorithm (intent to treat, noncompleters = failures) with the difference (95% confidence interval) between arms of 1.1% (-6.7% to 8.8%), indicating noninferiority of EFV/FTC/TDF vs. SBR. Similarly, maintenance of HIV-1 RNA <50 copies per milliliter by time to loss of virologic response algorithm was 87% vs. 85% for EFV/FTC/TDF vs. SBR, respectively [difference (95% confidence interval) 2.6% (-5.9% to 11.1%)]. Discontinuation rates were similar (EFV/FTC/TDF 11%, SBR 12%); more discontinuations for adverse events occurred in the EFV/FTC/TDF arm vs. SBR (5% vs. 1%), most commonly for nervous system symptoms. More patients withdrew consent in the SBR arm vs. EFV/FTC/TDF (7% vs. 2%). Estimated glomerular filtration rate (by Modification of Diet in Renal Disease) remained unchanged over 48 weeks in both arms (median change < 1 mL.min.1.73 m). A decrease in fasting triglycerides was observed at 48 weeks in the EFV/FTC/TDF vs. SBR arm (-20 vs. -3.0 mg/dL; P = 0.035). Adherence of > or = 96% was reported by visual analog scale in both arms at baseline and at all study visits. CONCLUSION: Simplification to EFV/FTC/TDF maintained high and comparable rates of virologic suppression vs. SBR through 48 weeks.