Sulggi Lee

This session covers recent data from adults and children with HIV evaluating the impact of first-line DTG- and/or TAF-based regimens on weight gain and metabolic complications. The sessions also describe results from switching to second-line PI- or NNRTI-based regimens as a means of potentially addressing these adverse metabolic effects.

Dr. Short presented the U.S.-based DEFINE study of 103 adults with prior >10% weight gain on INSTIs (DTG, BIC, EVG/C, or RAL) who switched to PI-based (D/C/FTC/TAF) ART. While there was no significant change in weight gain, BMI, waist circumference, lipids, or DEXA results, data were only available to 24 weeks, and TDF was not compared. Dr. Musiime presented pediatric data from CHAPAS-4 (Uganda, Zambia, Zimbabwe), where switching from DTG- to PI (DRV/r, ATV/r, or LPV/r)-based regimens showed superior virologic suppression (>400 copies/mL) with DTG, as well as with TAF/FTC (vs. ABC/3TC or ZDV/3TC). Weight-for-age increased for all drugs except LPV/r. LPV/r was associated with increased total and LDL vs. other non-backbone drugs. Dr. Venter presented on two studies: NAMSAL (Cameroon, 613 adults, TDF/3TC+DTG vs. TDF/3TC/EFV 400 mg) and ADVANCE (South Africa, 1053 adults, TAF/FTC+DTG, TDF/FTC+DTG, TDF/FTC/EFV 600 mg). Both studies demonstrated increased treatment-emergent hypertension (>140/90) over 192 weeks, but only in ADVANCE where hypertension was routinely treated, were these differences mitigated. Dr. Byonanebye demonstrated data from the RESPOND study (Europe, Australia, 9,704 adults) also showing that INSTI-based regimens were associated with hypertension while TAF-based regimens were associated with dyslipidemia. However, only hypertension remained significant after adjusting for time-updated BMI.

These studies further support prior reports of increased weight gain with DTG- and TAF-based first-line ART regimens, but it remains unclear if switching to second-line ART is an optimal approach for reducing potential metabolic complications. Furthermore, weight gain due to a “return to health” versus enhanced risk of metabolic complications are important to consider, especially in children, given superior virologic suppression rates with first-line regimens. Finally, there is an urgent need to potential alternatives to switching ART, including newer antihyperglycemic medications with significant anorectic properties, although this may be hampered by high cost, lack of target population data, and accessibility.