Change in Body Weight and Risk of Hypertension after Switching from Efavirenz to Dolutegravir in Adults Living with HIV: Evidence from Routine Care in Johannesburg, South Africa

Abstract

Background: The integrase strand transfer inhibitor(INSTI) dolutegravir is recommended in WHO guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy(ART) in Johannesburg, South Africa.

Methods: Prospective cohort study of adults(>16 years) with HIV who initiated ART between January 2010-December 2020. Patients were propensity score-matched 1:1(exposed i.e. remaining on efavirenz: unexposed i.e. switching from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index(BMI), blood pressure, and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and blood pressure 12 months after exposure.

Result: We matched 801 patients switching to dolutegravir to 801 remaining on efavirenz. Exposed patients had a higher mean(2.80 kg; 95% confidence interval(CI):2.37-3.23 kg) change in weight from baseline to 12 months vs. unexposed. Age, time on ART and BMI were important effect modifiers, with the largest mean change in weight in older age categories(40-49.9 and >50 years), those on ART longer(>24.0 months), and those in pre-obese(25-29.9 kg/m2) and obese BMI categories(>30 kg/m2). We found no difference in the risk of elevated blood pressure between exposed and unexposed groups.

Conclusion: In a real-world population, patients gained more weight after switching from efavirenz to dolutegravir than those remaining on efavirenz. We found no difference in the risk of elevated blood pressure. Longer follow-up is needed to determine if weight gain is associated with long-term changes in non-communicable chronic diseases risk.

Funding: This study has been made possible by the generous support of the American People and the President’s Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.

Declaration of Interest: Dr. Venter’s unit receives funding from the Bill and Melinda Gates Foundation, SA Medical Research Council, National Institutes for Health, Unitaid, Foundation for Innovative New Diagnostics (FIND) and the Children's Investment Fund Foundation (CIFF), has previously received funding from USAID, and receives drug donations from ViiV Healthcare, Merck, J&J and Gilead Sciences for investigator-led clinical studies. The unit does investigator-led studies with Merck, J&J and ViiV providing financial support and is doing commercial drug studies for Merck. The unit performs evaluations of diagnostic devices for multiple biotech companies. Individually, he receives honoraria for educational talks and advisory board membership for Gilead, ViiV, Mylan/Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, J&J, Sanofi and Virology Education. All others have nothing to declare.

Ethical Approval: Use of data was approved by the Human Research Ethics Committee of the University of the Witwatersrand (M140201). Approval for analysis of de-identified data was granted by the Institutional Review Board of Boston University (H-29768).

Keywords: integrase strand transfer inhibitors, dolutegravir, efavirenz, weight, hypertension, South Africa