Abstract Body

Background:

Weight gain has been associated with the use of antiretrovirals (ARV), especially with integrase inhibitors (INSTI) and tenofovir alafenamide (TAF), but less so with non-nucleoside reverse transcriptase inhibitors (NNRTI). In 2018, doravirine (DOR) became the latest NNRTI to be approved. We assessed changes in weight over time after starting DOR among virologically suppressed individuals.

Methods:

From the US-based OPERA cohort, ART-experienced adults with HIV who started a DOR-based regimen between 30AUG2018-30NOV2022 with a viral load <50 copies/mL were included (followed through 31MAY2023). Univariate linear mixed models were used to estimate rates of weight change on DOR; restricted cubic splines on time provided flexibility. Results were stratified by sex. Two sensitivity analyses were conducted to account for use of other ARVs before and after DOR start (a) restriction to those who maintained the same INSTI-TAF combination (b) stratification by efavirenz [EFV]-tenofovir disoproxil fumarate [TDF] use.

Results:

Of 388 included individuals, 79% were men, 33% were Black, and 78% were overweight or obese (BMI ≥25 kg/m2) at DOR start. Most regimens prior to DOR start included an INSTI with TAF (47%) or an INSTI without TAF (31%); 16% included TAF without an INSTI and 7% included neither INSTI nor TAF. DOR was combined with both INSTI and TAF (31%), with INSTI without TAF (30%), with TAF without INSTI (11%) or with neither (28%). Overall, people starting DOR lost a statistically significant average of 0.80 kg/year (95% CI: -1.32, -0.28; Fig 1). Both women and men experienced a statistically significant weight loss; women (70% Black) lost weight at a rate of -1.67 kg/year (95% CI: -3.32, -0.02), and men at a rate of -0.60 kg/year (95% CI: -1.12, -0.08; Fig 1). Among those who had the same INSTI-TAF combination throughout, there was a statistically non-significant trend toward weight loss. When EFV and TDF were absent both before and after DOR start, DOR was statistically significantly associated with weight loss.

Conclusions:

In one of the first real-world analyses of weight changes among virologically suppressed individuals who started a DOR-based regimen in the US, DOR was associated with a modest but statistically significant weight loss overall. Weight loss in women is of particular significance given that weight gain has often been associated with female sex. These findings are clinically meaningful given that most individuals included were overweight or obese at DOR start.