Study finds initial reductions in weight, lipids among ART-experienced people switching to doravirine plus INSTI

The off-label combination of doravirine (DOR) with an integrase strand transfer inhibitor (INSTI) could improve metabolic parameters in some heavily treatment-experienced people living with HIV (PLWH), according to initial results from a small retrospective study conducted in Italy.

About This Study

“Doravirine plus Integrase Strand Transfer Inhibitors as a two-drugs treatment-switch strategy in PLWH: the real-life DORINI multicentric cohort study” was published online on Sept. 27, 2023, in Journal of Acquired Immune Deficiency Syndromes. The lead authors are Mariacristina Poliseno, M.D., of the Unit of Infectious Diseases in the Department of Medical and Surgical Sciences at the University of Foggia, Italy, and Maria Mazzitelli, M.D., Ph.D., of the Infectious and Tropical Diseases Unit at Padua University Hospital, Italy.

Key Research Findings

This retrospective, multicenter, cohort study assessed off-label use of DOR with either raltegravir (RAL) or dolutegravir (DTG) in 95 treatment-experienced PLWH (52 on RAL and 43 on DTG). Sixty-four percent of participants were men, and participants had a mean age of 58 years with a median of six prior antiretroviral treatment regimens over a mean 22 years of living with HIV.

At baseline, 53% of participants had hypertension, 60% had dyslipidemia, and 8% were experiencing viral failure. Prior to switching, 50% of participants were on two-drug regimens and 78% of participants were taking an INSTI.

After a mean 37 weeks of follow-up, viral suppression rates were similar between the two arms, with one person in each arm stopping treatment due to virological failure. Additional discontinuations were due to poor tolerability (one in each arm) or death (two participants in the RAL arm).

Weight, waist circumference, and fasting lipids dropped among participants in both arms. Participants in the RAL group reported high satisfaction with their regimen, while those in the DTG group reported a significantly higher rate of adverse events, particularly neuropsychiatric side effects.

Discussion Highlights and Implications for Practice

Study limitations reported included the small sample size, retrospective nature of the study, and differences in the timing of study regimen initiation at the different sites.

The researchers concluded that results show the promise of these off-label combinations for certain older PLWH with drug interaction issues or comorbidities. However, they also emphasized that results are preliminary and need to be confirmed in controlled trials with more participants. In PLWH with adherence issues or viral failure who have certain resistance mutations, switching to DOR and an INSTI needs to be carefully evaluated.

By Barbara Jungwirth