Dolutegravir–lamivudine as initial therapy in HIV‐1 infected, ARV‐naive patients, 48‐week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study

作者：Pedro Cahn, María José Rolón, María Inés Figueroa, Ana Gun, Patricia Patterson, Omar Sued · 发表于：Journal of the International AIDS Society · 年份：2017 · DOI：10.7448/ias.20.01.21678 · 被引用次数：102 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV Research and Treatment

Abstract Introduction : A proof‐of‐concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two‐drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)‐naive patients. Methods : PADDLE is a pilot study including 20 treatment‐naive adults. To be selected, participants had no IAS‐USA‐defined resistance, HIV‐1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV‐1 RNA <50 copies/mL in an intention to treat (ITT)‐exposed analysis at 48 weeks (the FDA snapshot algorithm). Results : Median HIV‐1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686–36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T‐cell count was 507 per cubic millimetre (IQR: 296–517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm 3 (IQR: 180–...