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Weight Gain With ART—Return to Health or Introduction of Pathology?

Daniel R. Kuritzkes, MD

Chief, Division of Infectious Diseases
Brigham and Women's Hospital
Harriet Ryan Albee Professor of Medicine
Harvard Medical School
Boston, Massachusetts


Daniel R. Kuritzkes, MD, has disclosed that he has received consulting fees from Gilead Sciences, GlaxoSmithKline, Merck, and ViiV and funds for research support from Gilead Sciences, Merck, and ViiV.


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Released: August 11, 2020

Weight gain has been an important concern for patients who are initiating ART or among those changing from one regimen to another. A few studies at AIDS 2020 highlighted this concern and provided new insights to consider.

As we analyze the phenomenon, it is important to place this weight gain in context of weight gain observed in the population as a whole. That is, it is important to understand what part of the weight gain may be considered a return-to-health phenomenon and what may be a pathologic adverse event of the ARV regimen.

Investigators from the Kaiser Permanente cohort analyzed this question in a study comprising approximately 140,000 patients in their electronic health records database. They compared persons with HIV with a reference group of persons without HIV on a 1:10 ratio during a 12-year period. They used change in body mass index (BMI) as a surrogate measure for change in weight. They observed that persons without HIV had a modest gain in BMI of 0.06 kg/m2/year from an average of 28.7 kg/m2 at baseline to an average of 29.4 kg/m2 at the end of the 12-year period. Those with HIV started off with much lower average BMI (25.8 kg/m2) and had a gain in BMI of 0.22 kg/m2/year to an average of 28.4 kg/m2 after 12 years. That is, at the end of the 12-year period, the average BMI of the 2 groups was similar but during that period, there had been a statistically significantly greater rate of increase among the persons with HIV (P < .001). Whether this steeper change reflects an undesirable effect of ART or whether persons with HIV were just “catching up” is difficult to determine from these data.

The investigators went on to look at 3 different subgroups of patients stratified by BMI at baseline: normal/underweight (< 25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obese (> 30.0 kg/m2). In each of these groups, there was a substantial increase in average BMI among persons with HIV; in the normal weight and overweight groups, the rate of BMI increase was statistically significantly higher with vs without HIV. In the obese group, those without HIV showed a modest decrease in BMI whereas those with HIV showed a modest increase, with both groups reaching an almost identical average BMI after 12 years of 33.2 kg/m2 and 33.5 kg/m2, respectively. These findings suggest to me that there is a substantial component of weight gain in those with HIV that is a return to health once they start treatment, correcting for the metabolic and inflammatory consequences of HIV infection and allowing an increase in weight to levels similar to those seen in the population of persons without HIV.

Weight gain in persons with HIV who are receiving ART was also analyzed in the OPERA cohort through an exploration of electronic health records from more than 115,000 individuals in 65 cities in 19 US states and Puerto Rico. In this analysis, 5479 persons with HIV and ≥ 2 consecutive measures of HIV-1 RNA < 200 copies/mL switched the NRTI component of their ART regimen from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). The data showed that in the 9 months after the switch, there was an immediate and rapid increase in weight of approximately 2 kg. However, in looking at the weight curves as a whole, there was a slight continuing increase in weight during the 5 years before switching to TAF, then the bump at the time of switch, and then a return to the same slowly increasing weight curve. These data suggest to me that there is an effect of TDF that limits weight gain—perhaps because of subtle gastrointestinal effects that are not generally recognized or reported that may be limiting appetite or food intake in a very subtle way—and this limiting effect is released when TAF is substituted. After a short time, however, people re-equilibrate and return to the slow gain of weight over time that was occurring before the change to TAF. It is notable that this pattern was observed with the switch from TDF to TAF, regardless of the third agent in the regimen (INSTI, NNRTI, or boosted PI).

The bottom line from these studies and others is that people clearly gain weight on ART and that different regimens result in a different amount of weight gain. However, it is not at all clear what the mechanism of that weight gain is and to what extent the differences are explained by an appetite/metabolism suppressing or stimulating effect of individual regimens, or whether these effects are being mediated by some hormonal changes including weight-controlling hormones such as ghrelin or leptin. There is much more work to be done before we understand this phenomenon fully. The takeaway from these data is that patients and healthcare providers must be aware of the potential for weight gain and the importance of a well-balanced diet with an appropriate number of calories for one’s age and body habitus as well as a lifestyle that includes exercise.

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