Test Your Knowledge on HIV: ART and Weight Gain
Maile Young Karris, MD
Codirector, San Diego Center for AIDS Research Clinical Investigations Core
Department of Medicine
Divisions of Infectious Diseases & Global Public Health and Geriatrics & Gerontology
University of California San Diego
San Diego, California
Young Karis M. Test your knowledge on HIV: ART and weight gain. Consultant360. Published online July 28, 2021.
A 72-year-old woman recently relocated to be closer to her family and presented to your clinic to establish HIV care. Her medical history is significant for insomnia, depression, type 2 diabetes, and chronic hepatitis B virus.
She reported 100% adherence to her antiretroviral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Since starting her initial HIV regimen shortly after diagnosis (10 years ago), her HIV has been undetectable, and she has maintained a CD4 T-cell count of more than 500 cells/mL.
She also reported an 8.16-kg weight gain (body mass index, 32 kg/m2) since her previous doctor had switched her from efavirenz/emtricitabine/tenofovir disoproxil (EFV/F/TDF) 2 years ago. She is considering taking a break from her current antiretroviral therapy (ART) to lose some of the weight.
Answer and discussion on next page.
Correct answer: C. Switch her to doravirine/3TC/TDF (DOR/3TC/TDF)
Modern ART is highly active and, in general, well tolerated. However, several clinical and cohort studies support an association between greater weight gain with specific ART regimens, including integrase strand transfer inhibitors (INSTIs), specifically bictegravir and dolutegravir, as well as tenofovir alafenamide (TAF).1-3 Differential weight gain has been observed with ART initiation and ART switches (for adverse effects, simplification, and minimization of drug interactions). Women, Black persons, and those aged 60 years or older are at higher risk for ART-associated weight gain.2-4
There are 3, 2-drug ART options approved for switching (DTG/3TC, DTG/RPV, and CAB + RPV-LA) in stable patients with HIV, whom have no resistance to ART included in the regimens. However, all these regimens include an INSTI. Additionally, none of these regimens can durably suppress chronic hepatitis B virus infection and are thus contraindicated in this patient.5
Clinical trials are currently ongoing to evaluate the impact of switching ART on weight gain, but thus far, there is insufficient evidence that switching to specific ART regimens will result in subsequent weight loss. There is also emerging evidence that weight gain after ART initiation is associated with the development of comorbidities, including diabetes and cardiovascular disease.6,7 Thus, lifestyle counseling on nutrition and exercise is the primary recommended treatment for ART-associated weight gain. In this case, however, the patient is considering stopping ART because of the adverse effect. In this situation, it is reasonable to switch stable patients with HIV without HIV resistance to non-INSTI, non-TAF regimens. Due to her reported insomnia, use of EFV/F/TDF is relatively contraindicated, thus the best choice of the listed options would be DOR/3TC/TDF.
The Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV further discuss ART-associated weight gain, particularly as it relates to women with HIV.8
1. Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2020;71(6):1379-1389. https://doi.org/10.1093/cid/ciz999
2. Lake JE, Wu K, Bares SH, et al. Risk factors for weight gain following switch to integrase inhibitor-based antiretroviral therapy. Clin Infect Dis. 2020;71(9):e471-e477. https://doi.org/10.1093/cid/ciaa177
3. Mallon PW, Brunet L, Hsu RK, et al. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc. 2021;24(4):e25702. https://doi.org/10.1002/jia2.25702
4. Kerchberger AM, Sheth AN, Angert CD, et al. Weight gain associated with integrase stand transfer inhibitor use in women. Clin Infect Dis. 2020;71(3):593-600. https://doi.org/10.1093/cid/ciz853
5. Corado KC, Caplan MR, Daar ES. Two-drug regimens for treatment of naïve HIV-1 infection and as maintenance therapy. Drug Des Devel Ther. 2018;12:3731-3740. https://doi.org/10.2147/dddt.s140767
6. Herrin M, Tate JP, Akgün KM, et al. Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr. 2016;73(2):228-236. https://doi.org/10.1097/qai.0000000000001071
7. Achhra AC, Mocroft A, Reiss P, et al. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Med. 2016;17(4):255-268. https://doi.org/10.1111/hiv.12294
8. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Updated June 3, 2021. Accessed July 28, 2021. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines