In a study published in International Journal of Antimicrobial agents, dolutegravir-based regimens in patients with acute HIV-1 infections who started antiretroviral therapy (ART) early showed good viro-immunologic efficacy. This efficacy was also found when nucleoside reverse transcriptase inhibitor (NRTI)-transmitted mutations were present.
To compare tolerability and viro-immunologic efficacy of dolutegravir-based regimens with those based on elvitegravir, raltegravir, protease inhibitor, non-NRTI (categorized as non-dolutegravir group), 43 patients with acute HIV infection were enrolled. Acute HIV infection was determined by the presence of the positive p24 antigen with negative or indeterminate Western blot.
Patients were assigned to the dolutegravir and non-dolutegravir groups, comprising 20 and 23 patients respectively. Nine patients in total, 4 in the dolutegravir group and 5 in the non-dolutegravir group, were prescribed a 4-drug regimen. The median time between HIV diagnosis and the initiation of ART among patients was 12 days (interquartile range [IQR] 5-28), median age was 41 years (IQR 31-48), 81.4% were Italian and 83.7% were male.
Virus with transmitted mutations at baseline was detected in 7 patients, all of whom were in the dolutegravir group (P =.005). Two patients did not achieve undetectable HIV-RNA at the end of the study, 1 was lost to follow-up and the other had a viral load of 57 copies/mL. Time to virologic suppression was not different between study groups according to Kaplan-Meier analysis (log rank: P =.7155). Four patients stopped ART after achieving virologic suppression as a result of toxicity. Two receiving dolutegravir stopped as a result of neurologic toxicity and 2 receiving elvitegravir because of gastrointestinal toxicity.
The study was limited by its retrospective nature and relatively small numbers of patients. These are recognized problems when investigating ART in acute HIV infection because of complexities in obtaining large and homogenous sample sizes. Although no differences in prescribing between study centers was observed, residual selection bias cannot be excluded. Investigators noted that strengths of the work were the ability to recruit patients in a homogenous and very early stage of acute HIV infection and the further description of outcomes of dolutegravir therapy, something that had not yet been done.
Investigators concluded that in this study ART was started very early and dolutegravir showed good viro-immunologic efficacy compared to the other regimes. Further, for those treated with dolutegravir, “mutations for one of the NRTIs in the backbone does not seem to influence the virologic outcome, even with very high HIV-RNA values.”
Lagi F, Baldin G, Colafigli M, et al. Viro-immunological efficacy and tolerability of dolutegravir-based regimens compared to regimens based on other integrase strand inhibitors, protease inhibitors, non-nucleoside reverse transcriptase inhibitors in patients with acute HIV-1 infection: a multicenter retrospective cohort study [published online June 10, 2019]. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2019.06.003