HIV Persistence Reduced After Doubling Antiretroviral Therapy in Patients

A group of researchers examined the impact of doubling the dosage of the antiretroviral therapy (ART) dolutegravir in patients living with human immunodeficiency virus (HIV). Their findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023 in Seattle, WA.

Included in their study were 20 HIV-infected adults who received a triple therapy consisting of a dolutegravir dosage of 50 mg, plus abacavir and lamivudine and were fully suppressed for at least 2 years. Of the 20 patients, half of the group received an additional 50 mg of dolutegravir to intensify the treatment. The researchers collected peripheral blood mononuclear cells (PBMSCs), plasma, and rectal biopsies at different points over a course of 3 months.

According to the research team’s findings, the data presented no significant difference in total HIV DNA in PBMSCs nor in tissue during the study period for both groups. Although the researchers saw no significant differences, they did observe decreases in cell-associated unspliced HIV RNA in PBMCs (p = 0.020) and in ultrasensitive plasma viral load (p = 0.016) between day 0 and day 84 in the intensified group. No differences were observed in the control group, according to the researchers.

Although the researchers could not detect differences in immune activation or imflammation, the results show the potential for ongoing viral replication prior to doubling the dosage of dolutegravir. Further, the researchers note that the results should be confirmed in tissue where relevant to the treatment of HIV.

“We observed a decrease in unspliced RNA and ultrasensitive plasma viral load following [dolutegravir] intensification, suggesting ongoing viral replication in some participants,” the researchers concluded. “However, it had no measurable impact on chronic inflammation or immune activation. If confirmed in larger clinical trials, these results could have an impact on the clinical management of [people living with HIV].”

Reference:

Fombellida-Lopez C, Pasternak A, Cicillionytė A, et al. Doubling dolutegravir dosage reduces HIV persistence markers in ART-treated adults. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Accessed March 3, 2023. https://www.croiconference.org/abstract/doubling-dolutegravir-dosage-reduces-hiv-persistence-markers-in-art-treated-adults/