A study supports the current recommendation from the World Health Organization to use dolutegravir as first-line treatment for HIV, with efavirenz as an alternative option. However, the study also suggests that dolutegravir should be combined with TDF/FTC, which is associated with suppression of weight gain, and not with the newer combination of TAF/FTC, which is associated with excess weight gain and clinical obesity, especially in women.
For the ADVANCE research study, conducted in central Johannesburg in South Africa, over 1,000 participants were recruited from routine HIV services in and around the inner city area of Hillbrow. Data was cross-analyzed with two of the current Department of Health antiretroviral regimens, recommended in the 2019 ART guidelines, and a third regimen favored by higher-income countries. The newer regimens appeared to have side effect and resistance benefits over older regimens, and potential cost benefits, but little research had been done on non-Western populations with them.
All three regimens were very potent and well tolerated by patients; however, the newer regimens containing dolutegravir (DTG) and tenofovir alafenamide (TAF) demonstrated a large increase in weight, especially in women.
After 96 weeks of treatment, the percentage of people with viral suppression was 79% in the TAF/emtricitabine (FTC)+DTG arm, 78% in the TDF (tenofovir disoproxil fumarate)/FTC+DTG arm and 74% in the TDF/FTC/EFV (efavirenz) arm.
There were no significant differences in overall efficacy between the three treatments tested.
In terms of weight gain, after 96 weeks of treatment, men gained 5.4 kg in the TAF/FTC+DTG arm, 3.6 kg in the TDF/FTC+DTG arm, and 1.1 kg in the TDF/FTC/EFV arm.
For women, at the same time point, the weight gain was 8.1 kg in the TAF/FTC+DTG arm, 4.8 kg in the TDF/FTC+DTG arm, and 3.2 kg in the TDF/FTC/EFV arm.
The treatment emergent obesity for women at week 96 was 28% for those on TAF/FTC+DTG (5% for men), 18% for those on TDF/FTC+DTG (4% for men), and 12% for those on TDF/FTC/EFV (3% for men).
Dr Simiso Sokhela, lead clinician on the study, commented: “We are concerned about the weight gain and body composition changes which are more severe in women, and we have predicted new risk of associated diabetes and other complications, especially when taking both TAF and DTG together. The 96 week results supports the WHO treatment guidelines which reserve TAF only for patients with osteoporosis or impaired renal function.”
The study team suggest that service providers should consider the best options for patients to reduce their risk of long-term co-morbidities, and should consult with patient groups, researchers and other expert groups for guidance.