Weight changes with doravirine-based first line therapy
Given the concerns about weight gain with integrase inhibitors and NRTIs, especially dolutegravir and TAF, changes in weight and BMI should now be reported for other recently approved HIV drugs.
This is complicated because both starting ART and ageing are associated with weight gain and several studies have reported differences by gender, race and baseline HIV demographics.
This analysis for the NNRTI doravirine (DOR), presented by Chloe Orkin from Barts Health NHS Trust, London, used several ways to analyse changes including median and mean absolute changes, rates of people with more than 10% changes and changes in weight banding (ie change from underweight/normal to overweight/obese or from overweight to obese, etc).
The results generally showed no significant changes in treatment-naive adults for doravirine based ART, compared to DRV/r or EFV, with approximately 70% of people staying in the same weight category over 96 weeks. An important caution is that this was a post hoc analysis comparing different studies.
Doravirine data (at approved 100 mg dose) was compiled from three phase 2/3 studies in treatment naive adults.
- P007: DOR vs efavirenz (EFV) plus FTC/TDF
- DRIVE FORWARD: DOR vs darunavir/r (DRV/r) plus either FTC/TDF or abacavir/3TC
- DRIVE AHEAD: DOR/3TC/TDF vs EFV/FTC/TDF
The pooled groups included n=855 (DOR), 383 (DRV/r) and 472 (EFV) with results at 96 weeks. At baseline, median age was approximately 35 years old (+/– 10), 12–15% of participants were women and 18–23% were black. Mean weight and BMI were 76 (+/–15) kg and 25 (+/– 5.0).
At 96 weeks, mean and median weight increases were 2.4, 1.8 and 1.6 kg and 1.5, 0.7 and 1.0 kg, in the DOR, DRV/r and EFV groups respectively. This is similar to expected weight gains over time in the general population.
Percentage increases from baseline were similar for all three groups: approximately 68%, 17% and 15% had increases of <5%, 5 to 10% and >10% respectively.
Low baseline CD4 and high viral load correlated with a higher risk of >10% weight gain in all three groups.
Heat mapping graphs, excluding participants who were obese at baselines showed that 7%, 6% and 5% of participants became obese over 96 weeks, in the DOR, DRV/r and EFV groups respectively.
Sankey diagrams (showing direction of movement between categories) showed approximately 7% of participants with normal BMI at baseline became overweight but only 1% became obese. Slightly higher percentages of people who were overweight at baseline become obese on DOR (19% vs 13% vs 13%) – but with 10-15% returning to normal weight. Most people who were obese at baseline remained obese, although a higher percentage of people using DRV/r went back to just being overweight (though these were small absolute numbers).
The study concluded that weight gains in these studies were similar to those expected in an ageing population, with most people staying in the same weight category. However, there were relatively small percentages of women and black people, and objective measures including waist circumference and DEXA scan were not available.
Allowing for the important cautions for comparative post-hoc analyses, including baseline differences of some demographics between studies, the data are useful for not showing a signal of increased weight.
These results are helpful given the unexpected weight gain linked to dolutegravir and TAF in the ADVANCE study.
Orkin C et al. Effect of doravirine on body weight and body mass index in treatment naïve adults with HIV-1. 17th EACS, 16–18 October 2019, Basel. Oral abstract PS3/2.