Swapping out tenofovir disoproxil fumarate (TDF) for a newer version, tenofovir alafenamide (TAF), in HIV patients was more often associated with weight gain than when TAF was substituted for abacavir, researchers reported at the 2020 virtual IDWeek meeting.
In analyzing various switch protocols, researchers determined that gaining 3% of body weight or more per year occurred more frequently when TDF was dropped from patients’ regimens in favor of TAF rather when switching from abacavir to TAF.
Grace McComsey, MD, of Case Western Reserve University and University Hospitals Cleveland Medical Center, said her research suggested that TDF actually suppresses body weight.
That would be surprising, commented Joseph P. McGowan, MD, medical director for the Northwell Health HIV Service Line Program, Manhasset, New York. “Weight loss from tenofovir disoproxil fumarate has not been described to date, and, in fact, weight gain is usually found after starting any antiretroviral regimen,” he said. “This is likely from a ‘restoration to health’ effect, from suppression of ongoing viremia and dampening of immune activation.”
In the new study, 27% of 142 patients who switched from abacavir to TAF experienced at least a 3% increase in weight at one year, versus 40% of 828 patients who switched from TDF to TAF (P=0.003). A similar phenomenon was seen in subgroups who gained more than 5% or 10% of body weight, McComsey said in her oral presentation, but fell short of statistical significance.
“Even after adjusting for demographics, baseline CD4-positive cells, body mass index and switch to integrase inhibitor agents, the tenofovir disoproxil fumarate to TAF switch had a higher risk of weight gain of 3% or greater one year after the switch,” she said.
Her group scrutinized electronic medical records and prescription data from 10 HIV treatment centers that serviced more than 42,000 patients on antiretroviral therapy. All the patients were taking integrase inhibitors as their antiretroviral regimen backbone.
The two switch groups were balanced by race, sex, body mass index and CD4-positive count, but patients switching from TDF to TAF tended to be older. At baseline, more than 30% of both cohorts were overweight. About 80% of the groups were men.
She noted that one of the limitations of the study was that the impact of changes in diet, exercise, substance use, and concomitant medications and comorbidities were not accounted for in the analysis.
McGowan told MedPage Today, “This study addresses an issue of current concern regarding treatment with TAF and integrase inhibitors, especially when combined. Previous reports have linked weight gain to initiation with or switch to integrase inhibitors. Essentially all agents in the class have had some reports indicating this association. Some studies indicate that women and blacks are more likely to gain weight during integrase inhibitor therapy.”
“Recently TAF, which is the newer formulation of tenofovir that has a safer renal and bone mineral density profile, has been linked to weight gain both individually or if combined with integrase inhibitors and non-nucleoside reverse transcription inhibitors. The mechanism behind this weight gain is not known.”
“Clinically we have been including these data, although preliminary in nature, as they appear consistent across a number of trials, into discussion around shared decision making on initiation or switch of therapy,” McGowan said. “If weight gain is being managed, many patients may choose to adopt a therapeutic lifestyle intervention, work with a dietitian, and I have observed this to be effective in a number of patients.”
“There are no data to date that demonstrate a switch off integrase inhibitors or TAF would lead to a decline in weight,” he said. “If switches are made a goal should be clearly defined and patients closely monitored to ensure that virologic control is not lost.”
IDWeek is jointly sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.