Switching to TDF/3TC+DTG for first-line ART may improve metabolic outcomes in HIV

Switching from first-line tenofovir alafenamide (TAF) and emtricitabine (FTC) plus dolutegravir (DTG) to tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) plus DTG is associated with reductions in weight and cholesterol and triglyceride levels among individuals with HIV infection. These study findings were published in Clinical Infectious Diseases.

Researchers at the University of the Witwatersrand in South Africa conducted a study among patients with HIV infection who previously participated in the ADVANCE trial between July and November 2022. Metabolic profiles and weight were evaluated among patients who switched from first-line antiretroviral therapy (ART) with TAF/FTC+DTG, TDF/FTC+DTG, or TDF/FTC/efavirenz (EFV) to TDF/3TC+DTG for a minimum of 52 weeks.

Among a total of 1053 patients who participated in the ADVANCE trial, 172 were included in the analysis. Among patients receiving TAF/FTC+DTG (n=70), TDF/FTC+DTC (n=71), or TDF/FTC/EFV (n=31) as first-line treatment, 59%, 58%, and 77% were women; the median CD4 cell count was 560, 549, and 677 cells/µL; 98%, 97%, and 100% had an HIV viral load of less than 50 copies/mL; and the median BMI following the switch to TDF/3TC+DTG was 28.0, 25.9, and 25.6 kg/m², respectively.

Stratified by first-line treatment, significant decreases across several metabolic parameters were observed among first-line TAF/FTC+DTG recipients after switching to TDF/3TC+DTG. These included decreases in low-density lipoprotein cholesterol (LDL-C; mean difference [MD], -0.3 mmol/L; P =.000), total cholesterol (MD, -0.2 mmol/L; P =.0018), fasting glucose (MD, -0.2 mmol/L; P =.0003), HbA_1C (MD, -0.1 mmol/L; P =.0004), BMI (MD, -0.4 kg/m²; P =.0048), weight (MD, -1.2 kg; P =.0057), and triglycerides (MD, -0.1 mmol/L; P =.0254).

For patients who switched from first-line ART with TDF/FTC+DTC, the researchers observed significant increases in total cholesterol (MD, 0.2 mmol/L; P =.0009), systolic blood pressure (MD, 3.0 mm Hg; P =.0206), and high-density lipoprotein cholesterol (HDL-C; MD, 0.04 mmol/L; P =.0209).

Switching from TDF/FTC/EFV was associated with significant changes in LDL-C (MD, -0.3 mmol/L; P =.0012), HbA_1C (MD, -0.15 mmol/L; P =.0082), total cholesterol (MD, -0.3 mmol/L; P =.0113), weight (MD, 2.9 kg; P =.02), BMI (MD, 1.0 kg/m²; P =.0225), and HDL-C (MD, -0.1 mmol/L; P =.0495).

Increases in HIV viral loads were observed among 8 patients after switching to TDF/3TC+DTG. Of these patients, 1 did not re-suppress following adherence counseling and 4 were lost to follow-up.

Limitations of this study include the open-label design and the small sample sizes.

According to the researchers, “With weight gain persisting as a potentially major health complication with the use of all modern ART, risks for the development of long-term cardiac disorders remain of concern.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Bosch B, Akpomiemie G, Chandiwana N, et al. Weight and metabolic changes after switching from tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC+DTG and TDF/FTC/efavirenz (EFV) to TDF/lamivudine (3TC)/DTG. Clin Infect Dis. Published online December 15, 2022. doi:10.1093/cid/ciac949