A Phase-IV Non-interventional Study to Assess Virological Effectiveness,
Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1
Infected Indian Persons Living with HIV
Authors: Ashta Kuldeep K , Arora Sumit , Khanna Rajesh , Raman Nishant , Anilkumar Anirudh , Mohan Charu 
Published: January 2024

Background:
Dolutegravir (DTG) is a novel yet preferential first-and-second-line treatment
for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens
have not undergone a comprehensive, systematic evaluation regarding their real-world utilization
and safety profile among a sizeable Indian population.

Objective:
This study aimed to assess the 24-week immunovirological outcomes, anthropometric
and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART)
regimens.

Methods:
A single-centre phase-IV non-interventional observational study involving 322 ART--
naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed
up for outcomes at 24 weeks.

Results:
At 24 weeks, all PLH (n=113) in the naïve group, all PLH (n=67) in the first-line substitution
group, 93.9% PLH (n=46) in the first-line failure group, and 95.7% PLH (n=89) in the second-
line substitution group were virologically suppressed to plasma HIV-RNA <1000
copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50
copies/mL were consistent among PLH who received DTG as first- or second-line ART.
The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher
in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count
<350 cells/μL). Overall, 27.3% PLH (n=88) gained ≥10% of their baseline body weight, corresponding
to 3.7% incidence (n=10) of treatment-emergent clinical obesity [1]. DTG had an overall
lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside
analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors
(b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5
mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending
ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed
proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic
serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n=27) and 3.2%
(n=10) PLH, respectively. No apparent negative effects on renal function were detected.

Results:
At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution
group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the
second-line substitution group were virologically suppressed to plasma HIV-RNA <1000
copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50
copies/mL were consistent among PLH who received DTG as first- or second-line ART.

:
The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher
in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count
<350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding
to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall
lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside
analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors
(b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5
mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending
ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed
proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic
serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2%
(n = 10) PLH, respectively. No apparent negative effects on renal function were detected.

Conclusion:
Our results from a large Indian cohort indicate a favourable virological and
metabolic response, with good tolerance of DTG-based ART at 24 weeks.