Rapid weight gain after switching to TAF, regardless of other HIV drugs taken

People who switched to tenofovir alafenamide (TAF) from the previous version of tenofovir (tenofovir disoproxil fumarate – TDF) experienced rapid weight gain regardless of whether they were taking an integrase inhibitor or a drug from another class alongside TAF, analysis of a large US cohort shows.

The findings are presented as part of the virtual 23rd International AIDS Conference (AIDS 2020: Virtual) by Professor Patrick Mallon of St Vincent’s University Hospital, Dublin.

Weight gain after starting antiretroviral treatment has been reported in numerous cohorts and clinical trials but its causes are unclear. There are several explanations for the causes of weight gain. In part, weight gain is probably a 'return to health' effect, as it is more pronounced in people who start treatment with lower CD4 counts. Weight gain is more frequent and greater in black people, especially women, and might also be explained by genetic differences in metabolism of drugs that appear to suppress weight gain (efavirenz, TDF) or by differences in diet or baseline weight.

Studies have also linked specific antiretroviral drugs to weight gain. Dolutegravir and other integrase inhibitors have been associated with greater weight gain in clinical trials, but one trial has shown that weight gain was greatest in people starting treatment with both dolutegravir and TAF, suggesting either an additive effect of different drug classes or a misattribution of weight gain to a specific drug class.

Weight gain has also been seen after switching to integrase inhibitors, especially in women and black people.

Investigators wanted to determine whether switching from TDF to TAF resulted in weight gain and whether any specific drug classes combined with TAF had greater additive effects on weight, using data from OPERA, a large cohort combining data from clinics and medical practices treating around 8% of people diagnosed with HIV in the United States.

They identified 6919 patients in the OPERA cohort with undetectable viral load (< 200 copies/ml) who switched from TDF to TAF and who had pre- and post-switch weight measurements. The patients identified were predominantly male (approximately 80%) but in other respects broadly representative of people living with HIV receiving care in the United States (approximately 40% African American and 25% Hispanic).

The TAF switch group were stratified into four groups according to the third agent in their antiretroviral regimen: those who continued with an NNRTI (1454), those who continued with a boosted protease inhibitor (747), those who continued with an integrase inhibitor (3288) and those who switched from another drug class to an integrase inhibitor (1430). There were no significant demographic differences between the four groups, although people switching to a boosted PI or an integrase inhibitor tended to be older.

The investigators used longitudinal weight data gathered up to 48 months prior to switching and up to 36 months after switching to construct a model of weight changes adjusted for covariates, including interaction terms between age and sex to account for menopause, and race and sex to account for potentially greater weight gains observed in black women.

The investigators reported on results for an 'average' or referent patient in this population, who was a 45-year-old non-black man, with a baseline BMI of 27, a baseline CD4 cell count of 700, no endocrine disorders and not taking any other medication previously associated with weight loss or gain. The investigators did not model the weight gain patterns for groups of patients at higher risk, such as women or black people.

The average patient in this cohort gained 0.42kg a year on the old formulation of tenofovir (TDF) prior to switching (95% CI 0.26, 0.59). In the nine months after switching to TAF, the model showed a sharp increase in weight (+2.64kg [2.26, 3.01]) after which weight gain diminished to a level of +0.29kg a year (0.08, 0.51).

Comparing the three groups who maintained their third antiretroviral drug at the time they switched to TAF, the investigators found no substantial difference in weight gain. In all three groups, weight gain accelerated in the nine months after switching to TAF, before levelling out (+2.64kg in the integrase group, + 2.25kg in the NNRTI group and +1.81 in the boosted PI group). There was no significant difference between the three groups in the amount of weight gained after switching to TAF.

When they looked at the differences in weight gain in people who maintained integrase inhibitor treatment, the investigators found no significant difference in weight gain between people taking dolutegravir, elvitegravir or raltegravir.

Among those who switched to an integrase inhibitor (1430 switchers, most frequently from efavirenz, darunavir or atazanavir), the majority (78%) switched to elvitegravir, 12% to dolutegravir and 9% to bictegravir. Again, the study found no significant difference in weight gain between agents. Weight gain after switching to TAF was similar in people who maintained elvitegravir and those who switched to elvitegravir (+2.51, +2.55kg) in the nine months after switching.

These findings “suggest an independent effect of a switch from TDF to TAF on weight gain”, said Professor Mallon. The patterns of weight change were consistent across regimens, indicating that people who switched to TAF experienced an early and rapid weight gain in the nine months after switching, followed by a slowing or plateauing of weight gain.