Should INSTI- or TAF-Related Weight Gain Prompt a Switch?

Should INSTI- or TAFRelated Weight Gain Prompt a Switch?

BY DAVID WILD

Roughly 15% of people living with HIV gain more than 10% of their body weight in the first one to two years of treatment with an integrase strand transfer inhibitor (INSTI) or tenofovir alafenamide (TAF) regimen, leaving clinicians with the clinical question of whether to switch to a non-INSTI or non-TAF regimen. The answer is unclear, experts said.

“I would argue that physicians should generally not switch patients from an INSTI regimen only in light of weight gain, mainly because we don’t know what regimen we should switch these patients to, or if it will help,” said Kristine Erlandson, MD, MS, an associate professor in the Division of Infectious Disease at the University of Colorado Denver, Anschutz Medical Campus.

To be sure, a pooled analysis that her team conducted suggests that switching to an INSTI or TAF regimen does appear to contribute to the problem of weight gain, regardless of the regimen type (Clin Infect Dis 2021;73[8]:1440-1451). Her group found that 6.4% of individuals who switched from a variety of regimens to a newer regimen gained at least 10% of their body weight, compared with 2.2% of those who remained on their regimen.

“While switching from abacavir to TAF was associated with somewhat less weight gain, it should be noted that abacavir is not a great option for patients with numerous cardiovascular disease risk factors like diabetes, hypertension and hyperlipidemia,” Dr. Erlandson said.

For clinicians considering a change to a protease inhibitor (PI)based regimen, Dr. Erlandson said observational data from a cohort of almost 23,000 antiretroviral treatment (ART)-naive patients with HIV showed that patients treated with a PI-based regimen gained only slightly less weight than using an INSTI-based regimen (J Int AIDS Soc 2020;23:e25484), while her group’s pooled analysis showed switching from a PI to an INSTI was similar in terms of weight gain as remaining on a PI (Clin Infect Dis 2021;73[8]:1440-1451).

“So, weight changes with protease inhibitors really aren’t that impressively better than integrase inhibitors,” Dr. Erlandson said.

While she has seen an increase in practitioners switching patients from an INSTI to a doravirine (DOR) regimen because of the concern about weight gain, Dr. Erlandson cautioned that “we really don’t have a lot of data to support that switch.”

Existing findings are mixed, with DOR initiation studies showing similar weight gains as would be expected in people without HIV (AIDS 2021;35[1]:91-99). In a single-switch study in ART-naive individuals randomized to start either DOR with a tenofovir disoproxil fumarate (TDF) backbone or efavirenz (EFV) with a TDF backbone, those who started EFV switched to DOR after 96 weeks. Participants experienced a 1- to 1.2-kg weight increase in either group at 96 weeks and 2 to 3 kg by week 192 (IAS 2021, abstract 709). “These weight gains are definitely less than what we saw in some of the other studies, but it’s also a different patient population, including fewer women and fewer racial and ethnic minorities,” Dr. Erlandson said. Switching from a three-drug regimen to a two-drug regimen does not appear to limit weight gain, Dr. Erlandson

added. Specifically, a recently presented study found that patients switching from one of several three-drug regimens to DTG/3TC experienced an average 2.1-kg weight gain, compared with an average weight gain of 0.6 kg among those who continued on their baseline three-drug regimen (IAS 2021, abstract 1457).

“One reason that some patients might experience impressive weight gain after a switch from some three-drug regimens is in part because we remove a weight-suppressive effect of EFV or TDF,” said Dr. Erlandson, adding that TDF-related weight suppression can be detrimental in pregnant women with HIV. Research indicates these patients gain less weight than recommended during pregnancy and can have more adverse pregnancy outcomes, including preterm delivery and neonatal mortality (Lancet 2021;397[10281]:1276-1292).

Rather than proceeding with a switch, Dr. Erlandson urged clinicians to first work with patients to institute lifestyle changes, including exercise and dietary modification.

“These modifications can have not only a significant effect on weight, but on physical function, strength and endurance as patients are aging, as well as control of metabolic issues like diabetes and hypertension, and they can reduce other comorbidities, such as sleep impairments or mood impairments,” Dr. Erlandson said.

The effects of INST-related weight gain can be significant, according to Darcy Wooten, MD, MS, an associate professor of medicine in the Division of Infectious Disease and Global Public Health at the University of California, San Diego.

She pointed to recent research showing higher 10-year risk for cardiovascular illness among patients on an INSTI-based regimen who gain weight (Conference on Retroviruses and Opportunistic Infections [CROI] 2021, abstract 117) and other data revealing a 22% increased likelihood of developing diabetes mellitus and hyperglycemia within six months of INSTI treatment, compared with similar patients not receiving an INSTI (hazard ratio, 1.22; 95% CI, 1.131.32), with the effect most pronounced among individuals receiving dolutegravir (CROI 2021, abstract 516).

Dr. Wooten does not encourage clinicians to switch patients to another regimen because of weight gain, but she said that “in certain patients who have gained a substantial amount of weight and have tried all the interventions, are still not able to lose weight or maintain their weight, and are considering stopping their medications, it would be appropriate to consider switching to an alternative regimen.

“That requires taking a patient-centered approach and explaining to the patient what’s known about this area, what the gaps are in the literature, and doing active and deep listening to understand what this person values, what their priorities are, and then developing a plan that utilizes shared decision making,” Dr. Wooten said. ■

Drs. Erlandson and Wooton spoke at the same session during the IDWeek 2021 virtual meeting. Dr. Erlandson reported relationships with Gilead, Janssen and ViiV Healthcare. Dr. Wooten reported no relevant financial disclosures.

C. diff Medications

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of patients treated at Michigan Medicine and 628 controls also treated at Michigan Medicine for diarrhea suspicious for CDI but who were negative for CDI (Anaerobe 2021 Sep 8. https://doi.org/10.1016/j. anaerobe.2021.102444).

They analyzed data for prescribed and over-thecounter non-aspirin NSAIDs within 30 days of CDI as well comorbidities and baseline laboratory findings. Patients with CDI and NSAID use were closely matched with non-CDI NSAID users according to sex, presence of back pain and arthritis, baseline serum creatinine, serum albumin, and use of anticoagulants or antiplatelet medications.

The results showed that 22% to 26% of those with or without CDI had used non-aspirin NSAIDs during the previous month, with analyses confirming there was no elevated CDI risk among those receiving NSAIDs (odds ratio [OR], 0.97; 95% CI, 0.72-1.29; P=0.816).

The only significant CDI risk factors they found were older age (OR, 1.09; CI, 1.01-1.17; P=0.02), scores on the weighted Elixhauser Comorbidity Index, a measure of comorbidity burden (OR, 0.98; 95% CI, 0.97-0.99) and prior CDI (OR, 2.64; 95% CI, 1.96-3.56).

“Both on unadjusted and adjusted modeling, our findings do not support an association between NSAID use and an increased risk for CDI,” according to the investigators.

Prior research on the topic that has found an association between NSAID use and CDI “had two major limitations, [including] inadequate assessment of over-the-counter NSAID use and failure to account for treatment assignment bias,” the team noted. “To our knowledge this is the first study of NSAID use as a risk factor for CDI to account for treatment assignment bias utilizing propensity score matching,” they added. “This is significant as it increases our confidence that our modeled risk of CDI is causally related to NSAID use itself, rather than the underlying indication for the NSAID use.” ■

There was a 2-fold increased risk for CDI during PPI use.

Source: Clin Infect Dis 2021;72(12):e1084-e1089

The sources reported no relevant financial disclosures.