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  AIDS 2022
July 29 - Aug 2
24th Intl AIDS Conference
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Weight Gain After Non-nucleoside Reverse
Transcriptase-to-Integrase Inhibitor Switch in the United States

  AIDS 2022 July 29-Aug 2 Montreal
Girish Prajapati1, Jenny Tse2, Xiaohui Zhao2, Aimee M. Near2, Princy Kumar3 1Merck & Co., Inc., Rahway, NJ, USA; 2IQVIA, Durham, NC, USA; 3Georgetown University Medical Center, Washington DC, USA
What's going on?
At this conference ADVANCE & NAMSAL 192 week study results were reported, I emailed out to NATAP listserve NAMSAL slide presentation & its now posted on the NATAP website. These studies find increased weight associated with DTG and also separately below in the ADVANCE study for TAF. This is not new, but - Let's review the information around this that has already been out there in discussion. We don't know for sure why these weight gains are occurring & what for sure is causing them. But there has been a lot of discussion around this over the past few years. TDF & EFV have been associated with keeping weight down. Switching to TAF from TDF has been associated with weight gain and it is thought because TDF was keeping weight down so switching to TAF just eliminating what was causing keeping weigh down, then inordinate weight gain might occur by eliminating weight suppressant TDF and substituting it with TAF. It is thought that both EFV & TDF might reduce appetite and that DTG might be better associated with a return to normal health & perhaps more normal appetite - don't underestimate the return to health explanation. As well the generic CYP2B6 genotype appears to be associated with EFV weight changes.
A study at CROI 2020 - webcast "Dolutegravir use is Associated with Higher Postpartum Weight Compared to EFV", found "women living with HIV on DTG have persistently higher weight through 18 months postpartum than those on EFV in Botswana but similar weight to HIV-uninfected women". In the abstract: In Africans starting EFV-based ART CYP2B6 metaboliser genotype was associated with weight gain and, in women, with changes in limb fat. The similar weight gain observed between CYP2B6 extensive metabolisers in the EFV/TDF/FTC arm and the DTG/TDF/FTC arm suggests off-target effects (e.g. mitochondrial toxicity) impairing weight gain in EFV slow/intermediate metabolisers could explain the greater weight gain observed with DTG in African trials.
Another study at CROI 2020, "CYP2B6 Genotype and Weight-gain differences Between DTG & EFV" - found this.