by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
July 14, 2020
Due to the COVID-19 pandemic, the world’s largest conference on HIV was presented virtually this year. The International AIDS Conference was first convened in 1985 and is held every other year under the guidance of the International AIDS Society. This conference continues to provide a forum for the intersection of science, advocacy, and human rights as they relate to the AIDS epidemic. Similar to CROI, the IAS conference provides a venue for advancing new research in HIV care and includes policies and educational programs to promote an evidence-based response to ending the epidemic. For the next few weeks, I will provide a short synopsis of key studies presented at this conference. Academy members are strongly encouraged to visit the conference web site https://www.aids2020.org/online-programme/ to view plenary sessions, oral abstracts and other presentations from AIDS 2020.
Significant weight gain as a side-effect of integrase inhibitors (INSTI) continues to be reported but tenofovir alafenamide (TAF), an increasingly used NRTI, has also been implicated. This longitudinal cohort study looked at weight changes in approximately 7,000 persons across 65 cities in 19 states and Puerto Rico. Subjects were switched from tenofovir disoproxil fumarate (TDF) to TAF while being maintained on their other current medications or in some cases also switched to an INSTI. The study adjusted for age, sex, race, baseline BMI, and endocrine disorders. Patients who were switched to TAF had weight gain of 1.9 to 4.5 kg/year which was seen in patients who were maintained on a PI or NNRTI as well as those switched to an INSTI. The weight gain tended to slow down or plateau by 9 months. This effect was observed across ART, regimens suggesting an independent effect of TAF on weight gain.
The ADVANCE trial: Phase 3, randomized comparison of TAF/FTC+DTG, TDF/FTC+DTG or TDF/FTC/EFV for first-line treatment of HIV-1 infection. Sokhela S. Abstract # OAXLB0104.
This open-label randomized trial from South Africa compared three 3 ART regimens -TAF/FTC+DTG, TDF/FTC+DTG and TDF/FTC/EFV and included 1053 subjects. The primary endpoint was HIV-RNA > 50 copies at 96 weeks. Although this was primarily an efficacy trial, the study also looked at weight gain during the trial. By intention-to-treat analysis, 79% of participants on TAF/FTC+DTG, 78% on TDF/FTC+DTG and 74% on TDF/FTC/EFV had viral loads of <50 copies/mL at week 96. Regarding weight gain, female patients taking TAF/FTC/DTG had a mean weight gain of 8.1kg at 96 weeks and 12.3 kg at 144 weeks. For male patients mean weight gain was 5.2kg at 96 weeks and 7.2kg at 144 weeks. Treatment-emergent metabolic syndrome at 96 weeks was seen in 8.4% of all patients on TAF/FTC +DTG compared to 5.9% on TDF/FTC + DTG and 3.9% on TDF/FTC + EFV.
Changes in body mass index over time in persons with and without HIV.
Silverberg M. Abstract #OAB0603.
Many adults with HIV exhibit increase in weight and thus body mass index (BMI) after initiation of ART. This was a cohort study of 8,256 HIV+ adult members of the Kaiser Permanente health care system who were in care from 2005-2016. These subjects were matched 10:1 to HIV-negative persons by age, sex, race/ethnicity, care location, and calendar year. The analysis was limited to those who had recorded a baseline BMI. The HIV-positive subjects included only those who newly initiated ART. The study compared changes in BMI over time for all subjects. This included overall BMIs and in three baseline BMI subgroups: underweight/normal (<25), overweight (25-29.9), and obese (>30 kg/m2). The mean baseline BMI was 29.3 for HIV- and 26.2 for HIV+. The average annual change in BMI was 0.06 for HIV- and 0.16 kg/m2 (P<0.001) for HIV+. For all baseline BMI categories, HIV+ adults had faster BMI increases over time compared with changes for HIV- adults. At 12 years, the average BMI was 28.4 for HIV-negative and 29.4 for HIV-positive persons.
I believe the overriding theme with these studies is that patients on ART continue to gain weight overtime and thus are increasing their risk of comorbidities including diabetes and CVD. The challenge going forward will be finding ways to mitigate these changes in our patients – the majority who are doing clinically very well on INSTI and TAF-containing regimens. Lifestyle interventions play a role but may not be enough to keep patients at normal BMI levels.
The author has no conflicts of interest to disclose.
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