RESUMEN
BACKGROUND: Treatment simplification strategies involving induction with a ritonavir (RTV)-boosted (/r) protease inhibitor regimen followed by simplification (without RTV) are appealing because they may offer sustained virologic suppression while minimizing potential long-term adverse effects associated with RTV. METHODS: This open-label, randomized, noninferiority study enrolled 515 antiretroviral therapy-naive patients to receive abacavir/lamivudine plus atazanavir/RTV (ATV/r) followed by randomization at week 36 (N = 419) to maintain or discontinue RTV for an additional 48 weeks. Eligibility for randomization required confirmed HIV RNA level below 50 copies/ml and no virologic failure. Protocol-defined virologic failure after week 36 was confirmed rebound of HIV RNA level at least 400 copies/ml. The primary endpoint was the proportion of patients with HIV RNA level below 50 copies/ml at week 84 (time to loss of virologic response). This study is registered with ClinicalTrials.gov number NCT00440947. RESULTS: At week 84, noninferiority of ATV to ATV/r (95% confidence interval around the treatment difference -1.75 to 12.48%) was demonstrated with 181 of 210 (86%) patients in the ATV group and 169 of 209 (81%) in the ATV/r group maintaining HIV RNA level below 50 copies/ml. During the randomized phase (weeks 36-84), 10 versus 14% of patients in the ATV and ATV/r arms, respectively, experienced a drug-related grades 2-4 adverse event with hyperbilirubinemia being the most frequently reported (4 versus 10%). The overall rate of protocol-defined virologic failure was 2%; no patient had virus that developed a major protease inhibitor mutation. CONCLUSION: ATV in combination with abacavir/lamivudine is a potent and well tolerated regimen in patients who have achieved initial suppression on an induction regimen and represents a viable treatment simplification strategy.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Adulto , Anciano , Fármacos Anti-VIH/administración & dosificación , Sulfato de Atazanavir , Recuento de Linfocito CD4 , Didesoxinucleósidos/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Piridinas/administración & dosificación , Ritonavir/administración & dosificación , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
PURPOSE: The ARIES study assessed safety and efficacy of an induction regimen with atazanavir/ritonavir (ATV/RTV) + abacavir/lamivudine (ABC/3TC) followed by simplification to ATV + ABC/3TC in antiretroviral-naïve patients. METHODS: This report includes a noncomparative analysis of all patients in the induction phase of the ARIES study through 36 weeks (clinicaltrials.gov: NCT00440947). This open-label study included 515 antiretroviral-naïve,HLA-B*5701-negative patients receiving a regimen of ATV 300 mg, RTV 100 mg, and ABC/3TC 600 mg/300 mg once daily for 36 weeks; eligible patients were then randomized to continue the induction regimen or simplify to ATV 400 mg plus ABC/3TC 600 mg/300 mg once daily. RESULTS: Eighty-six percent (442/515) of patients completed 36 weeks on study; 80% (410/515) achieved HIV RNA <50 copies/mL (84% and 76% of patients with baseline HIV RNA of < and >or=100,000 copies/mL achieved this endpoint). Virologic failure (VF) was uncommon (3%); treatment-emergent major protease inhibitor and nucleoside reverse transcriptase inhibitor mutations were detected in 0/15 and 4/15 patients, respectively. Median CD4+ cell increase was 171 (range, -176 to 718) cells/mm(3). Hyperbilirubinemia (13%), diarrhea (4%), nausea (2%), and rash (2%) were the most frequent drug-related Grade 2-4 adverse events. Few adverse events (3%) led to study discontinuation. CONCLUSIONS: Induction with ATV/RTV + ABC/3TC once daily provides an efficacious and well-tolerated regimen for the initial treatment of HIV.
Asunto(s)
Fármacos Anti-VIH , Didesoxinucleósidos , Infecciones por VIH/tratamiento farmacológico , Lamivudine , Oligopéptidos , Piridinas , Inhibidores de la Transcriptasa Inversa , Ritonavir , Adolescente , Adulto , Anciano , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Didesoxinucleósidos/uso terapéutico , Esquema de Medicación , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/enzimología , VIH-1/genética , Antígenos HLA-B/análisis , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Oligopéptidos/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , ARN Viral , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To compare the efficacy, durability, and tolerability of GW433908 (908), 1400 mg twice-daily (BID), with nelfinavir (NFV), 1250 mg BID. METHODS: This was an international, multicenter, randomized, open-label study (NEAT) in antiretroviral therapy (ART)-naive HIV-infected adults with plasma HIV-1 RNA (vRNA) at screening > or =5000 copies/mL (c/mL). Patients were randomly assigned to 908 or NFV (2:1) for a minimum of 48 weeks, with a background of abacavir (ABC) and lamivudine (3TC). RESULTS: A total of 166 patients received randomized treatment with 908 BID and 83 received NFV BID. The population was diverse with regard to race and gender (76% Hispanics and blacks, 31% female) and had advanced HIV disease at screening (45% had vRNA >100,000 c/mL, 48% had CD4 cell counts <200 cells/mm3, 20% had a history of Centers for Disease Control class C events). After 48 weeks of study by an intention-to-treat rebound or discontinuation = failure analysis, a greater proportion of patients in the 908 BID group (66%) than the NFV BID group (51%) achieved vRNA <400 c/mL. Furthermore, more patients with screening vRNA >100,000 c/mL (67 vs. 35%) or CD4 <50 cells/mm3 (48 vs. 24%) achieved undetectable viral loads taking 908 BID compared with NFV BID, respectively. Favorable immunologic responses were observed for both groups. Diarrhea, which was more common in the NFV BID group (18 vs. 5%), was the only drug-related grade 2-4 adverse event with a significant difference (P = 0.002) in incidence between groups. CONCLUSION: Administration of 908 BID resulted in a potent and sustained antiretroviral response, notably in ART-naive patients with advanced HIV disease. GW433908 was generally well tolerated and provides a convenient dosing option without food or fluid restrictions.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Nelfinavir/uso terapéutico , Organofosfatos/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Carbamatos , Didesoxinucleósidos/administración & dosificación , Quimioterapia Combinada , Femenino , Furanos , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , VIH-1/inmunología , VIH-1/aislamiento & purificación , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , Nelfinavir/efectos adversos , Organofosfatos/efectos adversos , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Sulfonamidas/efectos adversosRESUMEN
STUDY OBJECTIVE: To establish the clinical equivalence (noninferiority) of one tablet containing abacavir 300 mg-lamivudine 150 mg-zidovudine 300 mg (Trizivir) versus a tablet containing lamivudine 150 mg-zidovudine 300 mg (Combivir) given with one abacavir (ABC) 300-mg tablet, administered twice/day, in antiretroviral-experienced, human immunodeficiency virus (HIV)-1-infected patients. DESIGN: Randomized, open-label, parallel-group, multicenter, formulation-switch study. SETTING: Twenty seven outpatient treatment sites. PATIENTS: Adults with HIV-1 RNA levels of 400 copies/ml or less and CD4+ cell counts above 200 cells/mm3 who had been treated for 16 weeks or more with highly active antiretroviral therapy containing Combivir-ABC. INTERVENTION: Patients were randomized 1:1 to Trizivir (97 patients) or Combivir-ABC (98) for 24 weeks. MEASUREMENTS AND MAIN RESULTS: The primary study end point was the proportion of patients who maintained less than a 0.5-log10 increase from baseline in HIV-1 RNA (virologic success) through week 24. Clinical equivalence of the treatments was established if the 95.1% lower confidence limit (LCL) for the difference in proportion of virologic success with Trizivir minus Combivir-ABC was -0.12 or greater. Trizivir was clinically equivalent to Combivir-ABC. The intent-to-treat observed analysis at week 24 with Trizivir and Combivir-ABC showed a similar rate of virologic success (83% [80/97] and 77% [75/98], respectively, 95.1% LCL -0.026), of patients with HIV-1 RNA levels of 400 or fewer copies/ml (99% [82/83] and 93% [77/83], respectively, 95.1% LCL 0.021), and of patients with HIV-1 RNA levels of fewer than 50 copies/ml (89% [74/83] and 77% [64/83], respectively, 95.1% LCL 0.038). The intent-to-treat missing = failure analysis showed comparable results. Changes in CD4+ cell count from baseline, overall mean self-reported adherence (Trizivir 97%, Combivir-ABC 92%), and adverse events did not differ significantly between treatments. No ABC-related hypersensitivity reactions occurred. CONCLUSION: Trizivir was clinically equivalent to Combivir-ABC and may be substituted for the latter to simplify treatment and reduce pill burden.