Weight Gain Seen With TAF Regimen for HIV

Women with HIV tended to gain more weight than men when treated with an antiretroviral therapy that included tenofovir alafenamide (TAF) when compared with other standard-of-care therapies in South Africa, researchers reported.

Overall, men and women who received the combination that included TAF, dolutegravir, and emtricitabine experienced weight gain over the 144 weeks of the ongoing study — with women having a more pronounced increase, reported Simiso Sokhela, MBChB, an HIV treatment researcher at Ezintsha, Wits Reproductive Health & HIV Institute, which is part of the University of the Witwatersrand, based in Johannesburg, South Africa.

At the virtual meeting of the International AIDS Conference, Sokhela said, that over the course of the trial, women on the TAF regimen gained 12.3 kilograms (27.06 pounds), while women who were on a regimen of dolutegravir, emtricitabine, and tenofovir disoproxil fumarate — an older formulation of the drug — gained 7.4 kilograms (16.28 pounds), and women on efavirenz, emtricitabine, and tenofovir disoproxil fumarate gained 5.5 kilograms (12.1 pounds).

The weight gain in men followed a similar pattern, but was somewhat attenuated, Sokhela said. Men on the TAF regimen gained an average of 7.2 kilograms (15.84 pounds), while men who received the older tenofovir regimen gained 5.5 kilograms (12.1 pounds), and men on efavirenz, emtricitabine, and tenofovir disoproxil fumarate gained 2.6 kilograms (5.72 pounds).

At 96 weeks, patients on the TAF regimen were significantly more likely to be diagnosed with treatment-emergent metabolic syndrome compared with patients who were on the efavirenz treatment arm. Sokhela said 8.4% of both men and women were diagnosed with metabolic syndrome if they were on the TAF regimen compared with 3.9% of the patients on the efavirenz-based regimen (P=0.03). About 5.9% of those on the older tenofovir regimen were diagnosed with the syndrome, but that was not statistically different than the other arms.

The overall primary endpoint of the ADVANCE trial was suppression of HIV to undetectable levels, and Sokhela said that all three regimens were effective. At week 96 of the projected 192-week study, 79% of the patients on the TAF regimen had undetectable viral loads — based on the 50 copies/mL assay — compared with 78% of patients on the older tenofovir regimen and 74% of the patients on the efavirenz-based regimen.

“These results confirm current World Health Organization treatment guidelines, which reserve the TAF regimen only for patients with osteoporosis or impaired renal function,” Sokhela said at a press conference. She also noted that the 96-week results mirror and confirm the previously published 48-week results published last year.

Commenting on the results presented at the virtual meeting, Joseph P. McGowan, MD, medical director of the Northwell Health HIV Service Line Program in Manhasset, New York, told MedPage Today, “This study builds on growing concern for weight gain associated with HIV-1 integrase inhibitors, which has been previously reported. This finding may be a class effect, with some studies showing agents such as dolutegravir, raltegravir, and more recently bictegravir associated with weight gain.”

“The study does raise the possibility of an additive effect of combining TAF with dolutegravir on weight gain versus dolutegravir without TAF,” McGowan continued. “It should be noted that in pre-exposure prophylaxis studies of men who have sex with men/transgender women using TAF, weight gain was more common than among tenofovir disoproxil fumarate users, so this agent may cause weight gain by an independent mechanism.”

“Some weight gain is always expected after starting antiretroviral therapy, as a ‘restoration to health’ to some extent. The significance of the effect of the weight gain in this study can be seen in the higher proportion of recipients developing obesity and the metabolic syndrome, which can be associated with development of cardiovascular disease, fatty liver disease, and other long-term morbidities,” he noted.

In the ADVANCE study, researchers enrolled 351 patients in each treatment group, and the effectiveness analysis was based on intent-to-treat, Sokhela reported. Mean participant age was 32 and about 60% were women. Participants’ mean body mass index was 24.1 at baseline.

Sokhela noted that in areas where resistance to HIV treatment drugs is high — in South Africa it is estimated that 5% to 15% of the population has resistant virus — governments are opting for treatment with dolutegravir and TAF for both resistance and cost factors. She noted that in the 96-week data there was no finding of any resistance to integrase inhibitors.

She said that in women who become pregnant, 40% of those on TAF become clinically obese, which could have long-term effects on the health of both the mother and child.