Go slow before switching HIV meds due to metabolic effects

PHOENIX—The side effects of certain HIV medications, including weight gain and other metabolic changes, may be mild enough to be managed with lifestyle modification rather than switching patients to a different antiviral regimen, according to a small study by pharmacists at a health system in Virginia.

In a retrospective chart review of 100 adult patients on antiretroviral therapy (ART) seen at the Inova Juniper HIV Clinic, in Arlington, Va., pharmacists found largely nonsignificant weight gain or other changes, the researchers reported in a poster (abstract 19M) at the 2022 ASHP Summer Meetings and Exhibition.

Despite advancements, antiretroviral medications have been associated with metabolic side effects, said lead study author Haley Pressley, PharmD, a PGY-2 ambulatory care pharmacy resident at the hospital. She and her colleagues sought to determine the effect of ART in patients newly started on therapy and those who switched ART—specifically weight gain, body mass index, cholesterol, blood pressure and hemoglobin A1c.

The team found that patients using integrase strand transfer inhibitor (INSTI) therapy showed a nonsignificant increase in low-density lipoprotein cholesterol (LDL-C) from baseline to final lab value, for an average increase of 4.39 mg/dL versus 0.02 mg/dL with non-INSTI therapy (P=0.46). Total cholesterol increased by 9.4 mg/dL with INSTI therapy and 0.71 mg/dL with non-INSTI therapy, again not a significant difference (P=0.19).

Of the study population, 44% self-identified as African American, 36% Hispanic, 10% white, 2% Asian and 8% other. The average patient age was 46 years and 65% were male. Hemoglobin A1c, diastolic blood pressure, lipid panel, blood pressure, body mass index and weight were compared from the start or switch of ART out to various time points (six months and one, two, three, four, five and 10 years), from 2013 to 2022. Confounding variables such as smoking status, statin use, and use of antihypertensive or antidiabetic agents were recorded.

Patients who were on or switched to tenofovir disoproxil fumarate (TDF) had an average decrease of 1.88 mm Hg in diastolic blood pressure versus tenofovir alafenamide fumarate (TAF), which resulted in an increase of 0.73 mm Hg (P=0.391). Body mass index remained relatively stable in all patients, whether they were treated with an INSTI, TDF or TAF.

“What we concluded from this is we might be a little bit more inclined to keep patients on TAF therapy or INSTI therapy if they have had weight gain, and try more of the lifestyle factors [to control it],” Dr. Pressley said. “If a patient’s viral load is well controlled on their therapy, referring them to the pharmacy or others to help with weight loss management is probably the better option than trying to switch therapy.”

The study results highlight the need to customize therapy recommendations to each patient, Dr. Pressley said. “Future studies may focus on how these metabolic changes affect the development of comorbid conditions and on the metabolic effect of other antiretroviral medications.”

Dr. Pressley said the researchers plan to continue following the patients to gather additional data points, including any metabolic side effects of the injectable cabotegravir-rilpivirine (Cabenuva, Viiv Healthcare), approved in January 2021.

The research was interesting in that it didn’t see many of the same metabolic problems observed in larger populations, commented Daniel Chastain, PharmD, BCIDP, AAHIVP, a clinical associate professor at the University of Georgia College of Pharmacy and an infectious diseases pharmacist at Phoebe Putney Memorial Hospital, in Albany, Ga. “Maybe there are some patient-specific factors that influence some of these metabolic abnormalities that we see beyond just the individual drugs themselves,” he said. “But the benefits of integrase inhibitors certainly outweigh the potential harms.”

Still, it would have been helpful to have some additional data points, such as which HIV medications patients used before switching, or how many were new starts, Dr. Chastain noted. A study from earlier this year (Clin Infect Dis 2022 May 6;ciac355) found an increased incidence of new-onset diabetes after starting integrase inhibitors in HIV medication-naive patients of similar ages to those included in Dr. Pressley’s study, although her study did not seem to find this outcome, he said.

The ultimate question, Dr. Chastain said, is how the drugs affect cardiovascular disease: Are patients experiencing more cardiovascular events or are these just fluctuations in laboratory values and vital signs?

“We currently don’t have enough data to say that patients experiencing one of these negative effects [require] a switch in their HIV medications,” Dr. Chastain said. “But there’s certainly a possibility, so we always try to be preventative in terms of starting to talk to patients about the importance of diet and exercise earlier on, rather than waiting until things start to take place and then trying to chase it on the back end.”

By Karen Blum