ART Regimens Linked to Varying Weight Gains

By Marilynn Larkin, Reuters Health
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Multiple factors contribute to weight gain in people with HIV infection, including their antiretroviral therapy (ART), a pooled analysis suggests.

Long-term health is increasingly a focus of care for patients with HIV, said Dr. Moupali Das of Gilead Sciences in Foster City, California. Helping them maintain a healthy weight may help reduce the risk of noninfectious complications, such as heart disease, he added.


Stepping on scale. Source: Getty

"Overall, the (study) supports the idea of ART-related weight change," Dr. Das said by email. "However, it is important to note that weight increases among the participants were consistent with weight gain trends in the general population during the same time period."

Individuals with greater weight gain did not have clinically significant metabolic changes, he said.

Also, he noted, "Greater weight gain was observed with newer antiretroviral agents relative to older regimens, potentially suggesting a weight-change association with modern regimens that are better tolerated and/or trends towards increasing rates of obesity globally."

Dr. Das and colleagues performed a pooled analysis of weight gain in eight Gilead-sponsored phase 3 randomized controlled trials involving treatment-naïve people with HIV initiating ART between 2003-2015. Overall, there were 5,000 participants (mean age, about 37; about 90% men; about 60% white) and 10,000 person-years of follow-up.

All studies included visits every 12 weeks through week 96. At ART initiation, median BMI was 24.8 kg/m2; 16.3% were obese, 31.4% were overweight; and 52.2% were normal or underweight.

As reported online October 14 in Clinical Infectious Diseases, the 96-week median weight gain was 2.0 kg, with the greatest rate of weight gain occurring during the initial 48 weeks. Through 96 weeks, 48.6%, 36.6% and 17.3% of participants had at least 3%, 5%, and 10% weight increase from baseline, respectively.

Weight gain was greater in more recent trials and with the use of newer ART regimens. Baseline factors associated with weight gain included lower CD4, higher HIV-1 RNA, no injection drug use, female sex and black race.

Integrase strand transfer inhibitors (INSTIs) were associated with more weight gain than protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs); dolutegravir and bictegravir were associated with more weight gain than elvitegravir/cobicistat.

Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine.

However, weight gain was not observed in all participants - 30.2% lost weight.

The authors state, "Collectively our results suggest that there are demographic-, HIV- and treatment-related contributors to weight gain in (people living with HIV). Our findings raise the possibility that modern ART regimens with improved tolerability and potency may lead to weight gain in some (patients), necessitating increased clinical attention to the maintenance of healthy body weight, lifestyle modification, and exercise at ART initiation."

Dr. Das said, "None of our treatment trials contained placebo arms, but we have observed in HIV prevention studies in which individuals at risk for HIV have been randomized to ART or placebo, that weight gain is consistently approximately 1 kg per year across studies in placebo groups as well as in groups receiving emtricitabine/tenofovir alafenamide, whereas weight remained relatively unchanged in groups receiving emtricitabine/tenofovir disoproxil fumarate."

"Given the overall health benefits of long-term viral suppression and the contribution of a return-to-health phenomenon, our future research is focused on understanding the long-term health implications of weight gain in (people living with HIV), as well as mechanisms of weight gain across different antiviral regimens," he concluded.

Sara Bares of the University of Nebraska Medical Center in Omaha, author of a related editorial, told Reuters Health by email, "The analysis adds to the growing body of literature demonstrating that INSTIs and, more broadly, modern ART regimens, are associated with more weight gain than older ART regimens, especially in those with more advanced disease and particularly among those of black race and female sex."

"Additional studies evaluating the mechanism of the weight gain, weight gain in switch and PrEP trials, and the management of weight gain associated with ART are needed," she said. "The challenge for the clinician is to translate these findings into clinical practice at a time when many questions remain about the clinical implications of this weight gain."

"I view the findings from the analysis as a call to arms," she added. "As we continue to investigate the causes, consequences and management of weight gain following ART initiation and switch, we must strive to enroll sufficient numbers of women from diverse racial and ethnic backgrounds in order to allow for sex and race-stratified analysis."

The study was sponsored by Gilead Sciences. Six coauthors are employees and the receive fees from the company.

SOURCE: http://bit.ly/32OSsVY and http://bit.ly/2MNsYmz

Clin Infect Dis 2019.

 

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