Conference Coverage

Weight gain highest with integrase inhibitors for HIV



– Weight gain in HIV treatment is highest with integrase inhibitors, especially dolutegravir (Tivicay), followed by raltegravir (Isentress), according to a review of thousands of North American patients during their first 5 years of therapy.

Dr. Kassem Bourgi, infectious disease fellow at Vanderbilt University, Nashville, Tenn. M. Alexander Otto/MDedge News

Dr. Kassem Bourgi

People “starting integrase inhibitors are gaining significantly more weight than ART [antiretroviral therapy] naive patients starting NNRTIs [nonnucleoside reverse transcriptase inhibitors]. They are also gaining more weight than ART patients starting PIs [protease inhibitors],” however, the differences do not always reach statistical significance, said lead investigator Kassem Bourgi, MD, an infectious disease fellow at Vanderbilt University, Nashville, Tenn.

“This is clinically important as” integrase inhibitor-based “regimens are now recommended first line,” and, as people with HIV live normal lifespans, they “are at increasing risk for obesity, metabolic comorbidities, and cardiovascular disease,” just like the rest of the population, he said.

Dr. Bourgi’s presentation was one of several at the Conference on Retroviruses and Opportunistic Infections tackling the issue of ART-induced obesity. There was great interest in the topic, and his study wasn’t the only one to find an increased risk of excess weight gain with integrase inhibitors.

“This is a real-world issue, and this is what we are seeing in our patients; they are dealing with this every day,” explained moderator Jane O’Halloran, MD, when asked about the impressive audience turnout for the ART obesity session.

Dr. Jane O'Halloran, infectious disease fellow at Washington University, St. Louis M. Alexander Otto/MDedge News

Dr. Jane O'Halloran

“It’s not just weight gain; it’s the knock-on effects of that weight gain,” such as cardiovascular disease and diabetes, “which are certainly related to increased mortality” in the general population, and at least preliminarily, linked to ART. “Weight gain is good in HIV in cachectic patients, but [we have to tease] out that return to health phenomena versus people who overshoot that mark, [which] is potentially being suggested with” integrase inhibitors. “It’s important we get a handle on this,” said Dr. O’Halloran, an infectious disease fellow at Washington University, St. Louis.

Dr. Bourgi’s team turned to the North American AIDS Cohort Collaboration on Research and Design, which includes data on HIV patients throughout Canada and the United States, to compare weight gain outcomes among 24,001 people who started HIV treatment from 2007-2016; 49% started on NNRTI-based regimens, 31% on PIs, and 20% on integrase inhibitors. Elvitegravir (Vitekta) was most commonly used in the integrase group (45%), followed by raltegravir (35%), and dolutegravir (20%).

At 2 and 5 years, patients started on integrase inhibitors gained 4.9 and 6 kg, respectively, over their predicted weight, compared with 3.3 and 4.3 kg for NNRTIs, and 4.4 and 5.1 kg for PIs, adjusted for age, sex, race, cohort site, HIV acquisition mode, ART initiation year, and baseline weight, HIV-1 RNA, and CD4 cell count.

At 2 years among the integrase group, weight gain was 6 kg for dolutegravir, 4.9 kg for raltegravir, and 3.8 kg for elvitegravir; the weight gain for those on elvitegravir was comparable to that for those on PIs.

“Patients who started dolutegravir or raltegravir gained significantly more weight by year 2 compared with those who started elvitegravir,” Dr. Bourgi noted.

The mechanisms for the differences are unknown.

Integrase inhibitors are very well tolerated, so it could be that once on them, people feel so much better that, as one audience member put it, they just do “what everyone else does”: overeat. Dolutegravir also is associated with psychiatric symptoms, so maybe people on it are more likely to be taking psychiatric drugs that pack on the weight. Perhaps it’s something peculiar to the drugs. More work is needed on the issue, Dr. O’Halloran said.

Most of the subjects were men, and 38% were men who have sex with men. The median age at ART initiation was 42 years, and median weight body mass index 25 kg/m2. The median CD4 cell count was 303 cells/mm3.

The work was funded by Gilead, through an investigator sponsored grant. Dr. Bourgi didn’t say he had any disclosures.

SOURCE: Bourgi K et al. CROI 2019, Abstract 670.

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