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.

Recent Publications Summary

Recent publications on dolutegravir have focused on its use in HIV infection across multiple clinical settings, including first-line therapy, maintenance switching, pediatric dosing, and post-marketing surveillance. In a real-world Chinese cohort of treatment-naive people with HIV, dolutegravir plus lamivudine (DTG+3TC) showed virologic suppression comparable to bictegravir/emtricitabine/tenofovir alafenamide over 24 months, with similar weight change and cumulative metabolic abnormalities; although the crude incidence of eGFR decline was higher with DTG+3TC, adjusted analysis did not show an independent association with renal decline 42036350Apr. A separate real-world study also examined switching treatment-experienced patients from an INSTI-based triple-drug regimen to DTG/3TC, but the abstract only notes that Chinese real-world data in this setting are lacking 42124360May.

Longer-term maintenance data were reported from the VOLVER clinical trial, which evaluated virologically suppressed adults with historical or suspected lamivudine resistance who switched to DTG/3TC. Proviral DNA M184V/I was detected in a subset of participants, but two virological failures occurred only within the first 48 weeks, no treatment-emergent resistance was detected, and no further failures were observed through week 96 41665101Feb. In Japan, a 10-year prospective post-marketing surveillance study assessed the safety and effectiveness of single-agent dolutegravir and the fixed-dose combination dolutegravir/abacavir/lamivudine in people living with HIV, addressing the need for country-specific long-term evidence 41910934Mar.

Additional studies extended dolutegravir evaluation beyond standard adult HIV treatment. In children with HIV weighing at least 20 kg, pharmacokinetics and safety were examined for dolutegravir dosing according to World Health Organization guidelines, including in those with tuberculosis coinfection 41855524Mar. Model-informed simulations also explored twice-daily dolutegravir dosing for children with first-generation integrase strand transfer inhibitor resistance, predicting exposures within the therapeutic window and suggesting efficacy and safety similar to those seen in adults with HIV-1 and first-generation INSTI resistance 41634915Feb. In Lesotho, children and adolescents transitioned from lopinavir/ritonavir-based ART to dolutegravir-based ART were studied for treatment satisfaction and side effects 41467721Dec.

Beyond HIV, dolutegravir was investigated in a phase 2 controlled trial in adults with human T-cell lymphotropic virus type 1 infection, where it reduced HTLV-1 proviral load and improved neurological outcomes 41834485Mar.

What Changes, What Holds

1. Comparable suppression with DTG/3TC does not yet settle renal or metabolic tradeoffs in real-world use
REINFORCES The new cohort data support dolutegravir’s continued role in first-line and switch therapy, showing that DTG/3TC can perform similarly to another standard regimen in virologic control and overall metabolic outcomes. The renal signal is mixed rather than decisive: a crude excess of eGFR decline was seen, but it did not persist after adjustment. That leaves the baseline account intact while adding a caution that kidney effects still need longer, better-controlled follow-up 42036350Apr.

2. Lamivudine-resistance concerns appear less limiting for DTG/3TC maintenance than once feared
REINFORCES Longer follow-up in suppressed adults with historical or suspected lamivudine resistance strengthens the case for dolutegravir-based maintenance, because failures were rare, early, and not accompanied by emergent resistance. The finding does not overturn the established use of dolutegravir in switch strategies; instead, it sharpens the sense that archived M184V/I does not automatically preclude durable suppression in carefully selected patients. The remaining uncertainty is how broadly this can be generalized beyond the studied maintenance setting 41665101Feb.

3. Pediatric use is moving from extrapolation toward age- and resistance-specific dosing evidence
NEW DIRECTION The pediatric studies extend dolutegravir beyond the adult treatment settings emphasized in the Overview, adding direct pharmacokinetic and tolerability data in children, including those with tuberculosis coinfection, and simulation-based support for twice-daily dosing when first-generation integrase resistance is present. That does not contradict the established adult role; it shows that pediatric dosing is becoming a distinct evidence base rather than a simple downscaled version of adult practice 41855524Mar41634915Feb.

4. Dolutegravir is being tested as a potential therapy outside HIV
NEW DIRECTION The HTLV-1 trial opens a role that the Overview does not cover at all: use against a different viral infection with neurologic disease implications. Because this is outside the established HIV treatment framework, it does not revise the baseline account of dolutegravir as an antiretroviral for HIV; it instead suggests possible repurposing that would need replication and mechanistic clarification before it could be considered established 41834485Mar.

Overview update candidates: pediatric dosing evidence for children; including twice-daily dosing in first-generation INSTI resistance; and the possibility of broader maintenance use in selected patients with archived lamivudine resistance.