Dolutegravir-Based Therapy Is Noninferior to Continued PI-Based Therapy in HIV

Investigators analyzed the virologic efficacy and metabolic effect of dolutegravir-based therapy combined with NRTIs in substitution of protease inhibitor-based therapy in patients with a history of failure or intolerance to first-line combination ART.

The presence of M184V or other archived nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations does not reduce the efficacy of dolutegravir-based therapy, which is noninferior to continued protease inhibitor (PI)-based therapy in HIV, according to study results published in the International Journal of Antimicrobial Agents.

Current guidelines recommend that patients with HIV who experience virologic failure when receiving first-line non–NRTI-based antiretroviral therapy (ART) should start PI-based therapy to improve clinical outcomes. However, long-term use of PIs is associated with cardiovascular disease and several metabolic complications. The objective of this study was to examine the virologic efficacy and metabolic effect of dolutegravir-based therapy when combined with NRTIs in substitution of PI-based therapy in patients with a history of failure or intolerance to first-line combination ART.

In this single-center observational study, researchers reviewed data on patients aged ≥20 who received HIV treatment at the National Taiwan University Hospital between September 1, 2016 and April 30, 2017. Inclusion criteria were a history of virologic failure or intolerance to first-line non–NRTI-based therapy and continued boosted or unboosted PI-containing therapy with a plasma HIV-RNA load (PVL) of <200 copies/mL for ≥6 months.

The primary outcome was the number of patients with virologic nonresponse at week 48, defined as patients who stayed on PI- or dolutegravir-based therapy with plasma viral load ≥50 copies/mL, patients with 2 consecutive plasma viral loads of >400 copies/mL with PI- or dolutegravir-based therapy during observation, and patients who discontinued PI- or dolutegravir-based therapy because of viral rebound. Secondary endpoints were changes in lipid profile from baseline to week 48 and change of estimated glomerular filtration rate from baseline to week 48. Researchers performed multivariate analyses using a logistic regression model to identify factors associated with virologic nonresponse during the observation period.

Of the patients who tested positive for HIV (N=502) and were eligible for analysis in the study, 189 switched to dolutegravir-based therapy, whereas 313 patients continued to receive PI-based therapy. Patients in the dolutegravir group were younger than patients in the PI group (mean age, 40±10.2 years vs 44.6±10.7 years), more likely to have hepatitis C virus (17.6% vs 10.5%), and more likely to have a history of virologic failure (44.4% vs 19.5%).

At week 48, 85.2% of patients in the dolutegravir group and 85.3% of patients in the PI group achieved viral suppression. Two (1.1%) patients in the dolutegravir group and 12 (3.8%) patients in the PI group had virologic nonresponse, with a difference of −2.7% (95% CI, −5.5% to 0.5%). The presence of M184V mutation and other NRTI resistance-associated mutations did not increase the risk for virologic failure in either the dolutegravir or PI group. Also, compared with the PI group, patients who switched to dolutegravir-based therapy had statistically significant decreases in triglyceride and total cholesterol levels.

This study had several limitations. First, the switch to dolutegravir-therapy was not randomized, and baseline characteristics were not balanced between the dolutegravir and PI groups. Second, the majority of patients in this study remained virally suppressed for a median of 6 years before switching to dolutegravir-therapy. Third, only 44.4% of patients in the dolutegravir group had a history of virologic failure, and data on archived genotypic resistance were not available for all patients. Fourth, therapeutic drug monitoring of ART was unavailable, and researchers were unable to assess the adherence of patients who experienced viral rebound during observation. Lastly, this study evaluated dolutegravir-therapy in Taiwan only after its initiation.

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The study researchers concluded that the efficacy of dolutegravir-based therapy is not compromised by the presence of M184V or other archived NRTI resistance-associated mutations and that the switch to dolutegravir-based therapy in HIV is not inferior to continued PI-based therapy in terms of virologic effectiveness given the presence of NRTI resistance-associated mutations. They recommend future prospectively designed, properly controlled clinical trials to confirm their findings.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Chen GJ, Sun HY, Chang SY, et al. Effectiveness of switching from protease inhibitors to dolutegravir in combination with nucleoside reverse transcriptase inhibitors as maintenance antiretroviral therapy among HIV-positive patients. Int J Antimicrob Agents. 2019;54(1):35-42.