Today’s ART paradigm is characterized by the availability of potent drugs for HIV prevention and treatment, including second-generation integrase strand transfer inhibitors (INSTIs) like dolutegravir (DTG). INSTIs block the integration of viral DNA into the host genome, a critical step in HIV’s life cycle. The integrase (IN) gene, a highly conserved region of the HIV genome, plays a key role in the virus’s integration process and is targeted by INSTIs. Dolutegravir stands out for its superior efficacy, potency, high resistance barrier, and widespread use, particularly in resource-limited settings, making it a cornerstone of modern HIV treatment and a key contributor to achieving global epidemic control goals by 2030.
The wide-scale adoption of DTG-based ART in RLS, coupled with limited treatment options in case of failure, highlights the need to closely monitor the emergence and spread of DTG resistance to ensure long-term and sustained efficacy. Furthermore, as the selection mechanism of drug resistance mutations (DRMs) is subtype-dependent, HIV-1 integrase resistance patterns as well as natural polymorphisms might display distinct pathways in the frame of a broad diversity of HIV-1 clades.
We conducted a rapid review of recent literature (2023–2024) on global DTG resistance, analyzing 23 studies, including systematic reviews, scoping reviews, clinical trials, cohort studies, cross-sectional studies, and case reports. Overall, DTG resistance prevalence remains low: 0–1.9% in clinical trials, 0–14% in cohorts, and 0–27% in cross-sectional studies. Key mutations identified include R263K, G118R, N155H, and Q148H/R/K, with resistance influenced by prior treatment history and current formulations.
Six scenarios were associated with DTG resistance:
- ART-naïve individuals on DTG w/ 2 NRTIs
- ART-naïve individuals on DTG w/ lamivudine (dual therapy)
- ART-experienced individuals w/ virological failure (VF) on DTG & 2 NRTIs
- ART-experienced individuals w/ virological suppression on DTG & 2 NRTIs
- ART-experienced individuals w/ suppression on DTG & another ARV
- ART-experienced individuals w/ suppression on DTG monotherapy
Special considerations include (i) perinatally HIV-infected infants at risk of drug resistance from maternal ARVs or sub-therapeutic prophylaxis; and (ii) HIV/TB coinfected patients requiring careful regimen selection.
DTG remains highly effective with a strong barrier to resistance. While resistance rates are encouragingly low, ongoing surveillance is crucial.