Background: In India, following the implementation of the dolutegravir (DTG) based regimen, only a few studies compared the outcomes of DTG and efavirenz (EFV) based regimens. Therefore, this study aimed to assess virological suppression and gain in CD4+ counts of DTG and EFV-based antiretroviral therapy (ART) regimens.Methods: A retrospective study was conducted and the entire sample (n=140) was divided into two major classes as DTG group (n=70) and EFV group (n=70) further classified as tenofovir/lamivudine/dolutegravir (TLD) and tenofovir/lamivudine/efavirenz (TLE) regimen. Data was collected on socio-demographic characteristics, laboratory measures, and clinical and drug-related variables. For quantitative and qualitative data analysis, respectively, the T-tests and Chi-square tests were applied.Results: The mean CD4+ gain was comparable in both regimens after six months of ART but significant after 12 months of ART in the TLD group. Viral load suppression was achieved in 55.71% of clients in the TLE group after six months of ART while in the TLD group, 88.57% of clients achieved virologic suppression which was highly significant. Clients who remained on the DTG-based regimen gained significantly more weight at 12 months (mean +6.15 kg) as compared to the EFV-based regimen (mean +1.85 kg). After 12 months of ART, the majority of laboratory variables were unaffected by either regimen with the exception of serum creatinine and random blood sugar (RBS) in the TLD group.Conclusions: Our study provides real-life evidence of better outcomes of therapy with DTG over EFV in terms of viral load suppression but immunologic recovery is equivalent in EFV-based regimens after six months of treatment. We recommend the use of DTG only in clients with a high baseline viral load as it costs approximately twice as much as EFV when cost-effectiveness is taken into account.