Impact of switching to a dolutegravir-based regimen on body weight changes: insights from West African adult HIV cohorts

Abstract

Introduction: Adverse metabolic effects related to dolutegravir (DTG) are increasingly reported as countries are adopting DTG-based regimens as first-line antiretroviral therapy (ART), but there is limited data from sub-Saharan Africa. We explored changes in body weight pre- and post-switch to a DTG-based regimen and assessed the association between DTG switch and significant weight gain (SWG) defined as a ≥10% increase over a 12-month period in people living with HIV (PLHIV) on ART in West Africa.

Methods: We first included all PLHIV followed in the IeDEA West Africa cohorts between January 2017 and June 2021, with a documented switch to DTG during 2019-2021 and in care ≥36 months at the day of switch. Weight change was estimated using a two slope piecewise linear mixed model with change point at the switch date. Secondly, we emulated a sequence of target trials (ETT) based on the observational data, performing pooled logistic regression analysis to compare SWG occurrence between PLHIV who switched to DTG and those who did not.

Results: We first included 6705 PLHIV from Burkina Faso, Côte d'Ivoire and Nigeria. Their median age at the time of switch was 48 years (IQR: 42-54) with a median follow-up of 9 years (IQR: 6-12), 63% were female. Most patients switched from efavirenz (EFV)-based ART (56.6%) and nevirapine (NVP)-based ART (30.9%). The overall post-switch annual average weight gain (AAWG) was significantly elevated at 3.07 kg/year [95% CI: 2.33-3.80] compared to the pre-switch AWG which stood at 0.62 kg/year [95% CI: 0.36-0.88]. The post-switch AWG was greater in patients previously on EFV and protease inhibitor (PI)-based ART compared to those on NVP-based ART. The pooled logistic regression analyses of a sequence of 24 ETT, including 9598 person-trials, switching to DTG was significantly associated with an SWG (aOR = 2.54; 95% CI = 2.18-2.97).

Conclusions: In West Africa, a 12-month DTG exposure was associated with substantial weight gain, especially in PLHIV previously on EFV and PI-based ARTs. Continuous weight monitoring and metabolic profiling is imperative in HIV cohorts to delineate the long-term cardiometabolic impact of DTG as patients with, or at elevated risk for cardiovascular diseases might benefit from alternative ART regimens.

Keywords: HIV; West Africa; antiretroviral therapy; dolutegravir; observational cohort study; weight gain.

Figure 1

(a) Flow diagram of the selection of the studied populations (Analysis 1). (b) Selection of individuals for the emulation of a target trial, 2019–2020. ART, antiretroviral therapy; DTG, dolutegravir. *Non‐initiators of DTG could be included as initiators in subsequent trials if they initiated DTG and still met the eligibility criteria or several times as non‐initiators if they did not initiate DTG but still met the eligibility criteria.

Figure 1

(a) Flow diagram of the selection of the studied populations (Analysis 1). (b) Selection of individuals for the emulation of a target trial, 2019–2020. ART, antiretroviral therapy; DTG, dolutegravir. *Non‐initiators of DTG could be included as initiators in subsequent trials if they initiated DTG and still met the eligibility criteria or several times as non‐initiators if they did not initiate DTG but still met the eligibility criteria.

Figure 2

Weight evolution from month‐24 pre‐switch to month‐12 post‐switch to DTG according to sex, age and ART regimen pre‐switch. AAWG, annual average weight gain (in kg/year); EFV, efavirenz; NRTIs, nucleoside reverse transcriptase inhibitors; NVP, nevirapine; PI, protease inhibitor.