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Weight Change Following Switch to Dolutegravir for HIV Treatment in Rural Kenya During Country Roll-Out
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Hickey, Matthew D. MDa; Wafula, Erick MScb; Ogachi, Sabina M. BScb; Ojwando, Hellen Dipb; Orori, Gordon BScb; Adede, Richard O. BAb; Garraza, Lucas Godoy PhDc; Petersen, Maya L. MD, PhDd; Havlir, Diane V. MDa; Balzer, Laura B. PhDd; Ayieko, James MBChB, PhD, MPHb Regardless of mechanism, our study suggests that weight gain associated either with removal of EFV or addition of DTG may be attenuated in settings where there is not a widespread obesity epidemic and where food insecurity is common.
Variability in pharmacogenetics within and between populations may also contribute to heterogeneous weight gain observed with ART switch between individuals and across settings.12,23
In conclusion, our large multiclinic studies in rural Kenya demonstrated slightly greater than expected weight change following switch to DTG in women, but not in men. Individuals who were virally suppressed at switchdid not gain weight on DTG, compared with expected based on preswitch trajectory. In a small complementary prospective cohort study, mean glucose declined after DTG switch, and only 2% developed incident metabolic syndrome. Food insecurity was common and may have attenuated DTG-associated weight gain. Our findings suggest that DTG may not be associated with significant weight gain or metabolic complications among individuals switching to DTG-containing ART in rural sub-Saharan African settings where obesity is uncommon.

Switch to dolutegravir (DTG) in treatment-experienced people living with HIV (PLH) is associated with excess weight gain in some settings; data are limited from rural low-income settings with low obesity prevalence.
In rural Kenya, we conducted a retrospective cohort study at 8 HIV clinics and a single-site prospective cohort study including adults switching to DTG during countrywide transition to DTG/tenofovir DF(TDF)/emtricitabine as first-line HIV treatment. In the retrospective analysis, we used preswitch data to model postswitch weight trajectory had each participant not switched to DTG and contrasted observed vs. predicted postswitch weight. In the prospective analysis, we measured weight post-DTG switch and evaluated predictors of 6-month weight change.
Our retrospective cohort included 4445 PLH who switched to DTG between 2018 and 2020. Mean 12-month weight change was 0.6 kg preswitch and 0.8 kg postswitch. Among those on TDF throughout (n = 3374; 83% on efavirenz preswitch), 12-month postswitch weight was 0.7 kg more than predicted for women (95% CI: 0.4, 1.0) and similar among men (0.04 kg; 95% CI -0.3, 0.4). In our prospective cohort (n = 135, 100% female), mean 6-month weight change was +0.4 kg (IQR -1.1, 2.0 kg). Predicted gain varied by baseline food insecurity: +1.1 kg (95% CI: 0.34, 1.87) among food secure, -0.09 kg (95% CI -0.71, 0.54) among moderate insecure, and +0.27 kg (95% CI -0.82, 1.36) among severe insecurity.
In contrast to some reports of large weight gain following switch to DTG, we observed small weight increases in women and no weight change in men following DTG switch when on TDF throughout. Weight gain may be attenuated by food insecurity, though was modest even among food secure.

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