Efficacy of dolutegravir or bictegravir-containing therapy in a real-life cohort of people with HIV-1 sub-subtype A6.

OBJECTIVE

The objective of the study was to establish whether HIV-1 sub-subtype A6 (HIV-1A6) is a risk factor for virological failure in people with HIV (PWH) treated with the high genetic barrier integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) or bictegravir (BIC).

METHODS

The virological outcome of first-line DTG or BIC-containing antiretroviral therapy (ART) was assessed in 261 people with HIV-1A6 (PWH-1A6) and 1042 people with HIV-1B (PWH-1B) starting treatment between January 2014 and May 2025 with follow-up for at least one year in the EuResist Integrated Database.

RESULTS

Most PWH-1A6 were recent migrants from Ukraine. The event rates per 100 person-years follow-up were higher in PWH-1A6 for low-level viremia (LLV, 2.71 vs. 1.71, P  = 0.049) and virological failure with more than 1000 HIV RNA copies/mL (4.12 vs. 2.03, P  < 0.001) than in PWH-1B. At the end of follow-up, 226/261 (86.6%) PWH-1A6 and 936/1042 (89.8%) PWH-1B had viral load below 50 copies/ml ( P  = 0.132). INSTI DRMs were observed in 5/219 (2.3%) available integrase sequences of PWH-1A6, including two cases detected at virological failure with more than 1000 HIV RNA copies/ml and two cases in virologically suppressed PWH-1A6. In total, 12/261 PWH-1A6 discontinued DTG- or BIC-containing ART, including three individuals who were not virologically suppressed at discontinuation.

CONCLUSION

In PWH treated with DTG or BIC-containing first-line ART, LLV and virological failure with more than 1000 HIV RNA copies/ml were observed more frequently in PWH-1A6 than in PWH-1B. However, such events rarely resulted in INSTI resistance or discontinuation of INSTI-containing ART.