R
Should INSTIor TAFRelated Weight Gain Prompt a Switch? BY DAVID WILD
32
IDSE.NET
oughly 15% of people living with HIV gain more than 10% of their body weight in the first one to two years of treatment with an integrase strand transfer inhibitor (INSTI) or tenofovir alafenamide (TAF) regimen, leaving clinicians with the clinical question of whether to switch to a non-INSTI or non-TAF regimen. The answer is unclear, experts said. “I would argue that physicians should generally not switch patients from an INSTI regimen only in light of weight gain, mainly because we don’t know what regimen we should switch these patients to, or if it will help,” said Kristine Erlandson, MD, MS, an associate professor in the Division of Infectious Disease at the University of Colorado Denver, Anschutz Medical Campus. To be sure, a pooled analysis that her team conducted suggests that switching to an INSTI or TAF regimen does appear to contribute to the problem of weight gain, regardless of the regimen type (Clin Infect Dis 2021;73[8]:1440-1451). Her group found that 6.4% of individuals who switched from a variety of regimens to a newer regimen gained at least 10% of their body weight, compared with 2.2% of those who remained on their regimen. “While switching from abacavir to TAF was associated with somewhat less weight gain, it should be noted that abacavir is not a great option for patients with numerous cardiovascular disease risk factors like diabetes, hypertension and hyperlipidemia,” Dr. Erlandson said. For clinicians considering a change to a protease inhibitor (PI)based regimen, Dr. Erlandson said observational data from a cohort of almost 23,000 antiretroviral treatment (ART)-naive patients with HIV showed that patients treated with a PI-based regimen gained only slightly less weight than using an INSTI-based regimen (J Int AIDS Soc 2020;23:e25484), while her group’s pooled analysis showed switching from a PI to an INSTI was similar in terms of weight gain as remaining on a PI (Clin Infect Dis 2021;73[8]:1440-1451). “So, weight changes with protease inhibitors really aren’t that impressively better than integrase inhibitors,” Dr. Erlandson said. While she has seen an increase in practitioners switching patients from an INSTI to a doravirine (DOR) regimen because of the concern about weight gain, Dr. Erlandson cautioned that “we really don’t have a lot of data to support that switch.” Existing findings are mixed, with DOR initiation studies showing similar weight gains as would be expected in people without HIV (AIDS 2021;35[1]:91-99). In a single-switch study in ART-naive individuals randomized to start either DOR with a tenofovir disoproxil fumarate (TDF) backbone or efavirenz (EFV) with a TDF backbone, those who started EFV switched to DOR after 96 weeks. Participants experienced a 1- to 1.2-kg weight increase in either group at 96 weeks and 2 to 3 kg by week 192 (IAS 2021, abstract 709). “These weight gains are definitely less than what we saw in some of the other studies, but it’s also a different patient population, including fewer women and fewer racial and ethnic minorities,” Dr. Erlandson said. Switching from a three-drug regimen to a two-drug regimen does not appear to limit weight gain, Dr. Erlandson
