RESUMO
BACKGROUND: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24 RESULTS: Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups. CONCLUSION: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Organofosfonatos , Inibidores da Transcriptase Reversa , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Criança , Método Duplo-Cego , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Masculino , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir , Resultado do Tratamento , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
BACKGROUND: Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label extension phase. METHOD: Patients in 3 countries completing the d4T treatment phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the extension phase. RESULTS: At the time of switch, 100% and 99% of patients (n = 85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA <400 and <50 copies/mL. At 144 weeks after the switch, 89% (missing = failure) had HIV RNA <400 copies/mL and 87% had HIV RNA <50 copies/mL. Mean CD4 cell count increased 155 cells/mm3. No patient had virologic failure. Significant decreases from switch to week 144 in mean fasting total cholesterol (-22 mg/dL, p < .0001) and triglycerides (-78 mg/dL, p < .0001) were observed. Mean limb fat increased significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p < .0001). CONCLUSION: In virologically suppressed patients, switching d4T to TDF as part of a once-daily regimen with 3TC and EFV resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks, with significant improvements in metabolic parameters.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Estavudina/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Tecido Adiposo , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Argentina , Benzoxazinas/efeitos adversos , Brasil , Contagem de Linfócito CD4 , Colesterol/sangue , Ciclopropanos , República Dominicana , Feminino , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Organofosfonatos/efeitos adversos , Placebos/administração & dosagem , Estavudina/efeitos adversos , Tenofovir , Triglicerídeos/sangue , Carga ViralRESUMO
BACKGROUND: Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) to stavudine (d4T) in combination with lamivudine (3TC) and efavirenz (EFV) and an ongoing additional 336-week open-label extension phase. METHOD: Patients in Brazil, Argentina, and the Dominican Republic who completed the 144-week double-blind phase on TDF were eligible to roll over to the extension phase (weeks 144-480). Results from an interim week 288 analysis are presented. RESULTS: Eighty-six patients (62% male, 70% white) initially randomized to the TDF arm continued treatment with TDF. At the end of the 144-week, double-blind phase, 85 of the 86 had HIV-1 RNA <400 copies/mL, of whom 84% maintained virologic suppression through week 288. CD4 counts continued to improve with a mean increase of 135 cells/mm(3) from entry into the open-label extension to week 288. No patient discontinued due to renal adverse events. Small changes in bone mineral density at the lumbar spine and hip were seen in the first 48 weeks but were nonprogressive through 288 weeks. Mean limb fat increased from 8.0 kg at week 96 to 8.8 kg at week 288. CONCLUSION: Through 288 weeks, once-daily TDF+3TC+EFV demonstrated sustained antiretroviral activity with continued immunologic recovery. TDF treatment was not associated with renal adverse events or limb fat loss in antiretroviral-naïve patients.