Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

Abstract

Background Non-nucleoside reverse transcriptase (NNRTI) inhibitor-based antiretroviral therapy is not suitable for all treatment-naïve HIV-infected persons. Objective Perform a rigorous evaluation of three NNRTI-sparing initial antiretroviral regimens to demonstrate equivalence for virologic efficacy and tolerability. Design Phase-III, 1:1:1 randomized, open label, >96 week study. Setting Fifty-seven sites in United States and Puerto Rico. Patients Treatment naïve, ≥18 years, HIV-1 RNA >1000 copies/mL, no nucleoside reverse transcriptase or protease inhibitor resistance. Intervention Atazanavir 300 mg with ritonavir 100 mg, daily; or raltegravir 400 mg twice daily; or darunavir 800 mg with ritonavir 100 mg, daily; plus emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg daily. Measurements Virologic failure defined as confirmed HIV-1 RNA >1000 copies/mL between 16 and 24 weeks, or >200 copies/mL at or after 24 weeks; tolerability failure defined as discontinuation of atazanavir, raltegravir or darunavir for toxicity. A secondary endpoint was a combination of virologic efficacy and tolerability. Results Among 1,809 participants all pairwise comparisons of incidence of virologic failure over 96-weeks demonstrated equivalence within ±10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and a 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir respectively, primarily due to hyperbilirubinemia. For combined virologic efficacy and tolerability ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at time of virologic failure was rare but more likely with raltegravir. Limitations Open label; ritonavir not provided Conclusions Over 2 years all three regimens attain high and equivalent rates of virologic control. Regimens containing raltegravir or ritonavir-boosted darunavir have superior tolerability compared to the ritonavir-boosted atazanavir regimen. Primary Funding Source National Institute of Allergy and Infectious Diseases

A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

“…At entry, participants initiated ART per standard of care with standard doses of atazanavir/ritonavir + TDF/emtricitabine (FTC) [17]. ART change was allowed after study entry in the case of drug intolerance or virologic failure.…”

Modern antiretroviral regimens

“…Сравнение эффективности и безопасности схем, включавших ИИ или ИП, было проведено в исследовани-ях ACTG A5257 и FLAMINGO [5,6,9]. В исследовании ACTG A5257 1 809 больных ВИЧ-инфекцией, ранее не получавших АРТ, были рандомизи-рованы (1:1:1) в 3 группы.…”

“…Первую группу составили пациенты, получавшие RAL, вторую -дарунавир, усилен-ный ритонавиром (DRV/r), третью -атазанавир, усилен-ный ритонавиром (ATV/r). Пациенты всех групп также получали 2 препарата из группы НИОТ (TDF/FTC) [6].…”

“…При использовании ITT-анализа (без учета изменения схемы АРТ из-за развития НЯ) доля пациентов с неопределяемым уровнем РНК ВИЧ (<50 копий/мл) составила у больных 1 группы -94 и 94%; 2-й -89 и 90%; 3-й -88 и 90% соответственно. [6].…”

“…Использование в схемах АРТ препара-та RAL сопровождалось достоверно меньшим влиянием на уровни холестерина, липопротеидов низкой плотности и триглицеридов по сравнению со схемами, включавшими ИП (p < 0,001). Также результаты проведенного исследова-ния показали, что при терапии RAL отмечено менее суще-ственное снижение плотности костной ткани в области бедра (p = 0,005) и позвоночника (p < 0,001) [6].…”