Background: Based on the results of the GARDEL trial, we designed a proof of concept study to evaluate the antiviral efficacy, safety and tolerability of a dual therapy regimen with Dolutegravir (DTG) 50m mg QD plus Lamivudine (3TC) 300 mg QD as initial HAART among ARV-naïve patients
Methods: Pilot study including 20 HIV-infected ARV-naïve adults. Eligible participants had no IAS-USA defined NRTI resistance, HIV-1 RNA < 100.000 copies/mL at screening and negative HBsAg. Viral load (pVL) was measured at baseline, on days 2, 4, 7, 10, 14, 21, 28 and on weeks 6, 8, 12, and thereafter every 12 months up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA< 50 copies/mL in an ITT-exposed analysis at 48 weeks. (FDA-snapshot algorithm). Week 24 interim analysis was already presented at EACS 2015. Week 48 results are reported here.
Results: Median HIV-1 RNA at baseline was 24,128 copies/mL (IQR: 11,686-36,794). Albeit as per protocol, all patients had pVL< 100,000 copies/mL at screening, four patients had ≥100,000 copies/mL at baseline. Median CD4+ T-cell count was 507 per cubic millimeter (IQR 296-517). A rapid antiviral response was observed. (Median VL decay baseline-to week 12 was 2.74 logs). All participants had pVL < 50 copies from week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary end point of a pVL < 50 copies/mL. No major tolerability/toxicity issues were observed. Eighteen patients completed 48 weeks of the study, one patient (with undetectable viral load at last visit) committed suicide, in the context of a severe stress and emotional trauma deemed unrelated to study medication. One patient presented a low level protocol-defined confirmed virological failure at week 36., being the only observed failure. This patient resuppressed to pVL < 50 copies/mL prior to treatment intensification. Resistance tests revealed: RT:no emergent substitutions; Integrase: Not amplified
Conclusions: Dual therapy with DTG/lamivudine produced rapid virologic suppression with a favorable safety/tolerability profile in HIV-infected, treatment-naive individuals. Observed failure rate was 5%. This is the first report of a successful InSTI/lamivudine-based dual therapy in ARV-naïve patients after 48 weeks of treatment.