Introduction

Dolutegravir (DTG) is a potent second-generation integrase strand transferase inhibitor (INSTI), with high rates of viral suppression, low rates of treatment discontinuation and high genetic barrier to develop HIV drug resistance in treatment naïve patients living with HIV-1.

Aim

To evaluate the safety, tolerability, and efficacy of DTG 50 mg with Tenofovir Disoproxil Fumarate (TDF) and Lamivudine (300/300mg) fixed dose combination in treatment naïve adult Indian patients

Patient Profile

Patients with age ≥18 years, weight >40kg and confirmed and documented HIV-1 infection, receiving ART therapy for the first time (treatment naïve).

Methods

• Open label, multicenter, prospective, interventional, phase IV study
• Conducted at 14 sites between February 2019 and July 2020

Study endpoints

• The primary end point was to assess the incidence of adverse events (AEs)
• Secondary end points were to assess the proportion of patients achieving plasma HIV-1 RNA levels <50 copies/mL at week 24 and change in CD4+ cell count from the baseline.

Results

• The median (inter quartile range [IQR]) age and BMI of the cohort were 38.5 (18–70) years, and 22.2 (14.43–36.74) kg/m² respectively.
• The median (IQR) HIV-1 viral load (HIV RNA copies/mL) was 24,621.2 (10–5,500,145), and the mean CD4 cell counts (cells per cubic mL) (N = 249) was 350.3 ± 237.84
• Majority of the AEs reported were of mild or moderate severity
• One severe AE was reported in the form of anemia
• A single SAE (0.4%, pyrexia) was reported in one patient
• No deaths were reported throughout the study

Table 1: Overall Treatment Emergent Adverse Events

TEAE, treatment emergent adverse events; TESAE, treatment emergent serious adverse events

Table 2: Summary of Treatment Emergent Adverse Events by SOC and PT [> 2% Patients]

Efficacy

• By week 24, HIV-1 RNA load < 50 copies per mL was achieved by 86.8% patients ;89.1% (Full Analysis Set (FAS)complete cases), and 88.6% (Per Protocol Set; PP)
• The CD4 cell count showed marked improvements with an increase from 350.2 cells at baseline to 494.6 cells at week 24 with an average increase of 143.2 cells
• The proportion of patients with virological response were similar across FAS and PP [134.9 (SD-214.96) cells] sets for the CD4 cell count

Conclusion

• The study demonstrated that dolutegravir 50 mg administered along with fixed dose combination of TDF and lamivudine was safe, effective, and well-tolerated among Indian treatment naïve patients living with HIV-1
• Findings support DTG as the first-line standard of care for treatment naïve patients living with HIV-1 in Indian population

Reference