Jean Claude Katte, MD, MSc
Nominated From: University of Hawai’i
Research Site: University of Yaoundé
Research Area: HIV/Cardiometabolic Medicine
Primary Mentor: Gabriel Loni Ekali
Effect of Dolutegravir-based Antiretroviral Therapy on Metabolic Profile in Naïve Patients Initiating Treatment in Cameroon
Dolutegravir (DTG) is a next-generation integrase strand transfer inhibitor (INSTI) which has recently been approved for the treatment of human immunodeficiency virus (HIV) infection. Combined with tenofovir disoproxil fumarate and lamivudine in a single pill fixed-dose combination, DTG is cost effective with better tolerability, efficacy, durability and a high genetic barrier to resistance than Efavirenz. Since 2018, the World Health Organisation (WHO) has been supporting transitioning to DTG-based first-line regimens in low and middle-income countries (LMIC). By the end of 2019, 82 LMIC were reported to have transitioned to DTG-based HIV treatment regimens especially for antiretroviral treatment (ART)-naïve patients. Earlier studies with DTG-based treatment regimen have reported a possible link with neural tube defects in infants born to mothers who had taken the drug prior to conception. Although this association was not supported by new findings from studies conducted in Africa, other concerns were raised. In the NAMSAL (New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries) Study conducted in Cameroon in 2018, DTG-based ART regimen demonstrated non-inferiority compared with treatment with Efavirenz (EFV) (400mg). While this study also showed good tolerability of DTG-based treatment, there was however a significant increase in weight and body mass index (BMI) in the DTG-based treatment arm compared to the EFV-based arm. The ADVANCE trial, conducted in South Africa amongst ART-naïve participants also demonstrated that DTG-based regimen was associated to increases in weight and obesity. Increases in weight and the incidence of obesity may pose an increased metabolic risk with corresponding increase in glycemia, LDH-cholesterol, triglycerides and low HDL-cholesterol, although this has not been sufficiently elucidated. Also, in these studies, the effect of DTG-based treatment on visceral adipose tissue (VAT) was not studied meanwhile gain in VAT has been shown to be associated with increased metabolic risk independent of increase in weight and BMI. In addition, there is limited available data on the effect of DTG-based HIV treatment on other metabolic parameters such as glucose homeostasis and lipid profile. We therefore have designed a prospective observational study with a before-and-after analysis of ART naïve subjects in Cameroon who will receive a DTG-based HIV regimen as first-line treatment over a period of 6 months.
Understanding how DTG-based HIV treatment regimens affect all components of body composition (including visceral adiposity), glucose and lipid metabolism may provide guidance towards establishing an appropriate and tailored intervention to curb the metabolic risk.