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

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/mm3 (IQR: 180–462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low‐level protocol‐defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end‐of‐study visit without having changed the two‐drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV‐naive patients. Conclusions: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV‐therapy‐naive patients. ClinicalTrials.gov Identifier: NCT02211482.