Limited Weight Impact After Switching From Boosted Protease Inhibitors to Dolutegravir in Persons With Human Immunodeficiency Virus With High Cardiovascular Risk: A Post Hoc Analysis of the 96-Week NEAT-022 Randomized Trial

Abstract

Background In the NEAT022 trial, virologically suppressed persons with HIV at high cardiovascular risk switching from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D) showed non-inferior virological suppression and significant lipid and CVD risk reductions on switching to dolutegravir relative to continuing protease inhibitors. Methods Post-hoc analysis. Major endpoints were 48-week and 96-week weight and body mass index (BMI) changes. Factors associated with weight/BMI changes within the first 48 weeks of DTG exposure, proportion of participants by category of percent weight change, proportions of BMI categories over time, and impact on metabolic outcomes were also assessed. Results Between May/2014 and November/2015, 204 (DTG-I) and 208 (DTG-D) participants were included. Weight significantly increased (mean +0.810 kg DTG-I arm, and +0.979 kg DTG-D arm) in the first 48 weeks post-switch, but remained stable from 48 to 96 weeks in DTG-I arm. Switching from darunavir, white race, total-to-HDL cholesterol ratio <3.7, and normal/underweight BMI were independently associated with higher weight/BMI gains. The proportion of participants with ≥5% weight change increased similarly in both arms over time. The proportions of BMI categories, use of lipid-lowering drugs, diabetes and/or use of antidiabetic agents, and hypertension and/or use of antihypertensive agents did not change within or between arms at 48 and 96 weeks. Conclusions Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes.

Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi

“…We observed that patients receiving DTG-based regimens were more likely to transition from normal to overweight and observed a significant proportion from transitioning from overweight to obese within the 6-month follow-up period. These results highlight the importance of ongoing monitoring of patients receiving DTG regimens, as there may be implications for increased mortality due to non-communicable diseases among individuals receiving DTG-based treatment [ 10 , 12 , 20 ]. The transition to higher BMI categories among patients receiving DTG-based regimens emphasizes the need for comprehensive healthcare interventions that address not only HIV treatment but also management of associated comorbidities [ 12 ].…”

Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease

“…Switching from tenofovir disoproxil fumarate (TDF) to TAF has also been associated with significant weight gain in PLWH. 316,317 One of the proposed mechanisms of weight gain is due to the reduction of plasma HIV RNA levels and mitigating the catabolic effects associated with viremia; therefore, a restorative process leading to improved health occurs. As a result, some individuals experience weight gain that exceeds normal, healthy levels.…”

Beyond the Numbers: Weight Gain Risk Factors, Implications, and Interventions among Individuals with HIV

“…Numerous observational studies, retrospective analyses, and large randomized clinical trials have suggested that INSTIs, particularly DTG and BIC, may be associated with more weight gain compared to other ARVs. Within the INSTI class, previous studies have observed varying patterns of weight gain [41,43,[60][61][62][63][64][65][66][67]]. An early study exploring differences in weight gain between INSTIs and other ARVs was the STARTMRK study.…”