Weight Gain Following Initiation of Antiretroviral Therapy:
Select Data From a Pooled Analysis
Pooled analysis of 8 randomized, phase 3 clinical trials to explore the demographic-, HIV-1-, and treatment-related contributors to weight gain*:
- The analysis was sponsored by Gilead Sciences
- All trials were randomized, with an active-controlled design and follow-up for at least 96 weeks
- Eligible participants were treatment-naïve adults who initiated ART between 2003 and 2015
- The pooled population comprised 5680 patients and more than 10,000 person-years of follow-up
ARVs Associated With an Increased Risk of ≥10% Weight Gain
Among NRTIs assessed, TAF was the only one associated with an increased risk of ≥10% weight gain. The initiation of BIC or DTG, EVG/c, or RPV (but not ATV/r) was associated with an increased risk of ≥10% weight gain.
Association Between ARVs and ≥10% Weight Gain†
Mean Weight Gain Over 96 Weeks—Specific INSTIs and NRTIs
Observed Mean Weight Gain With ART Use
*P≤0.05, BIC compared to EVG/c;
*P≤0.05, DTG compared to EVG/c
At 96 weeks, participants taking BIC or DTG experienced similar weight gain, both greater than in participants taking EVG/c (LS mean weight gain: BIC, 4.24 kg [95% CI 3.71-4.78]; DTG, 4.07 kg [95% CI 3.51-4.62]; EVG/c, 2.72 kg [95% CI 2.45-3.0]).
*P≤0.05, TAF compared to AZT; *P≤0.05, ABC compared to AZT; *P≤0.05, TDF compared to AZT
Among NRTIs, TAF was associated with the greatest weight gain (LS mean weight gain: TAF, 4.25 kg [95% CI 3.94-4.56]; ABC,
3.08 kg [95% CI 2.36-3.81]; TDF, 2.07 kg [95% CI 1.84-2.30], as compared to AZT 0.39 kg [95% CI –0.57-1.34]).
LIMITATIONS OF DATA
- These data came from trials not designed to prospectively assess the impact of ART on weight gain
- These analyses did not evaluate other potential contributors to weight gain, such as psychiatric comorbidities, concomitant medications, diet, exercise, or smoking habits
- No body composition data to determine anatomical distribution of weight gain
- Generally, patients received newer third agents with newer NRTIs, making it difficult to assess individual agent effects
- Two years of follow-up may not be long enough to capture longer-term metabolic consequences of weight gain
- For the ≥10% weight gain analysis, results for DTG and BIC were combined and not presented individually
Weight increase has been reported during postmarketing use of dolutegravir.
For more information on the antiretroviral agents listed above,
please consult their respective Prescribing Information.
*The following 8 randomized, phase 3, Gilead-sponsored trials were included in the analysis: GS-US-01-934, GS-US-236-0102, GS-US-236-0103, GS-US-264-0110, GS-US-292-0104, GS-US-292-0111, GS‑US-380-1489, GS-US-380-1490.
†This was a multivariate model; stepwise model selection was used to identify which baseline risk factors were associated with significant (≥10%) weight gain in individuals initiating ART. As a result, CD4, HIV-1 RNA, BMI, sex, and race were selected. Odds ratio and its 95% CI, P values were from the logistic regression model including baseline categories of CD4, HIV-1 RNA, BMI, sex, and race as risk factors; third agent and NRTIs as fixed effects.
ABC=abacavir; ART=antiretroviral therapy; ARV=antiretroviral; ATV/r=ritonavir-boosted atazanavir; AZT=zidovudine; BIC=bictegravir; BMI=body mass index; CI=confidence interval; DTG=dolutegravir; EFV=efavirenz; EVG/c=cobicistat-boosted elvitegravir; INSTI=integrase strand transfer inhibitor; LS=least squares; NRTI=nucleoside reverse transcriptase inhibitor; RPV=rilpivirine; TAF=tenofovir alafenamide fumarate; TDF=tenofovir disoproxil fumarate.
Reference: Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2019. doi:10.1093/cid/ciz999.