dolutegravir

Overview

Dolutegravir is an antiretroviral drug in the integrase strand transfer inhibitor class and is used in the treatment of HIV infection. By inhibiting HIV integrase, it blocks a key step in the viral life cycle: the insertion of viral DNA into the host genome. This mechanism makes dolutegravir a central component of modern antiretroviral therapy, including first-line regimens and switch strategies for people living with HIV.

Clinically, dolutegravir is used both as a standalone agent within combination therapy and in fixed-dose combinations such as dolutegravir/lamivudine and dolutegravir/abacavir/lamivudine. Recent research has continued to evaluate its effectiveness, tolerability, metabolic effects, and broader virologic or immunologic impacts in diverse populations, including treatment-naive adults, treatment-experienced patients, children and adolescents, and people receiving long-term post-marketing care.

Focus of Latest Publications

Recent publications on dolutegravir have focused on its role in antiretroviral therapy across multiple clinical settings, with particular attention to treatment switching, first-line regimen comparisons, pediatric dosing, and post-marketing safety. In treatment-experienced people with HIV-1, one real-world study examined switching from an INSTI-based triple-drug regimen to dolutegravir/lamivudine, reflecting ongoing interest in simplified maintenance therapy. Another Chinese cohort compared bictegravir/emtricitabine/tenofovir alafenamide with dolutegravir plus lamivudine as first-line regimens in ART-naive patients, reporting comparable virologic suppression over 24 months, similar weight changes, and similar cumulative metabolic abnormalities between groups. Although crude EGFR decline appeared more frequent with dolutegravir plus lamivudine, adjusted analyses did not show an independent association with renal decline.

Additional publications have addressed longer-term safety and effectiveness in routine practice and special populations. A 10-year post-marketing surveillance study in Japanese people living with HIV evaluated single-agent dolutegravir and the fixed-dose combination dolutegravir/abacavir/lamivudine, aiming to provide country-specific evidence on safety and effectiveness. In children with HIV, pharmacokinetic and safety data were assessed for dolutegravir dosing according to World Health Organization guidelines, including in those with tuberculosis coinfection. Related pediatric work also used population pharmacokinetic modeling to support a weight-tiered twice-daily dolutegravir dose for children with first-generation integrase strand transfer inhibitor resistance, predicting exposures within the therapeutic window and suggesting efficacy and safety comparable to adult experience.

Beyond HIV treatment, dolutegravir has also been studied in other viral and neurologic contexts. A phase 2 controlled trial evaluated dolutegravir in adults with human T-cell lymphotropic virus type 1 infection, assessing effects on proviral load and clinical neurological outcomes. In children and adolescents with HIV in Lesotho, investigators examined tolerability after programmatic transition from lopinavir/ritonavir-based therapy to dolutegravir-based ART, focusing on treatment satisfaction and potential side effects. Together, these studies highlight continued interest in dolutegravir as a versatile therapy with expanding evidence across adult, pediatric, and real-world settings.