Virological failure not associated with initial ART regimen in Europe/Australia study

Virological non-suppression two years after starting antiretroviral therapy (ART) is associated with high baseline viral load and low CD4 count, but not with the use of any specific ART regimen, according to results from a large study out of Western Europe and Australia.

About This Study

“Plasma HIV-1 RNA and CD4+ T-cell counts are determinants of virological non-suppression outcomes with initial integrase inhibitor-based regimens: A prospective RESPOND cohort study” was published online on April 13, 2023, in Clinical Infectious Diseases. The lead author is Hortensia Álvarez, M.D., of the Department of Internal Medicine in the Infectious Diseases Unit of the Complexo Hospitalario Universitario de Ferrol in Coruña, and of the Department of Biochemistry, Genetics and Immunology at Universidade de Vigo, both in Spain. Study authors include one employee from three financial supporters of the study: ViiV Healthcare, Gilead Sciences, and Merck Sharp & Dome.

Key Research Findings

This analysis of data from the multi-country RESPOND prospective cohort study in Europe and Australia investigated baseline factors for virological non-suppression in 4,310 people living with HIV (PLWH) who started ART between 2014 and 2020. Eighty-four percent of participants were men, 69% were white, and 61% were men who have sex with men. Median age was 38 years, with 19% of participants > 50 years old. In this study, non-suppression was defined by viral blips, persistent low-level viremia, residual viremia, and virological failure.

Seventy-two percent of participants started on an integrase strand transfer inhibitor (INSTI)-based regimen. At 96 weeks, 93% of participants were virally suppressed (48 weeks: 91%). Viral loads >100,000 copies/mL and CD4 counts <200 cells/μL at baseline (indicating late treatment start) were associated with viral non-suppression in all initial regimens.

Viral suppression was significantly less likely on darunavir compared to dolutegravir at week 48, but not at week 96. In participants starting treatment late, abacavir/lamivudine was associated with a shorter time to viral failure compared to tenofovir disoproxil fumarate/emtricitabine, as well as with lower viral suppression rates at week 96. In unadjusted analyses, rilpivirine was associated with a longer time to non-suppression, but this was not true after adjustment.

Discussion Highlights and Implications for Practice

The authors reported study limitations including potential bias in who was prescribed which regimens, as well as a lack of data on more recent antiretrovirals or two-drug regimens. They also pointed out strengths of this study such as the inclusion of a large number of INSTI-based participants and the ability to compare individual drugs within ART classes.

Results suggest that the size of the viral reservoir prior to starting ART determines virological failure, independent of treatment regimen, the researchers wrote. They called for additional research into the impact of newer antiretrovirals on viral suppression.

By Barbara Jungwirth