Transmission of Dolutegravir resistance in treatment-naive individuals with HIV-1: A cohort study

Dolutegravir (DTG) is widely used as a first-line Antiretroviral Therapy (ART) due to its high efficacy and safety. However, concerns about DTG resistance persist. This study investigated the prevalence and factors associated with transmitted DTG resistance in treatment-naive HIV-1-infected individuals in Brazil.

The study followed 150 treatment-naive HIV-1 individuals from May 2019 to May 2022 at a reference center for HIV/AIDS in Rio de Janeiro, Brazil. Baseline characteristics, viral load, and CD4 + cell counts were assessed. Genotypic resistance testing was conducted on plasma samples at baseline, and viral load was monitored during follow-up visits.

One hundred and thirty-one patients completed the study. The mean age was 37.73-years; 107 were male, and 24 were female. The median baseline of viral load was 4.33 log (21,193 copies/mm³), and CD4 + count was 342 cells/mm³, with the lowest count being 8 cells/mm³. The mean CD4 + count increase was 112 cells/mm³ (p < 0.01). One hundred and nine patients achieved an undetectable viral load three months after starting ART, with only eight patients not reaching undetectable levels by six months (42‒106 copies/mm³). The most common early adverse effect was nausea (12.9 %), and the most common later effect was increased creatinine levels (9.1 %), leading to the suspension or substitution of Tenofovir Disoproxil Fumarate (TDF). Genotyping was successfully performed on 85 patients: 66 were subtype B, 9 subtype C, 8 subtype F, and two CRF47_BF, with no resistance mutations and one accessory mutation (T97A).

This study did not demonstrate transmitted DTG resistance among treatment-naive HIV-1-infected individuals. The findings suggest that DTG remains a safe and effective first-line ART option. However, close monitoring of viral load is recommended for all patients on DTG-containing ART regimens. Additionally, genotypic resistance testing should be performed on individuals who experience virological failure or a significant decline in CD4 + cell counts, with close attention to ART adherence.