Obesity, a rising problem in HIV treatment

Patients with HIV find themselves in obesity situations, as the weight gain is favored not only by the therapy but also by their social and geographical environment.

Obesity has many consequences for the health of those affected. John R. Koethe, Vanderbilt University Medical Center, Nashville, TN, USA, presented the current state of research at the CROI 2019.

Obesity is characterized by a Body Mass Index (BMI) greater than 30, while a BMI between 25 and 30 indicates overweight. The prevalence of obesity is increasing worldwide. "We will not only become more numerous but also weigh more as a species," Koethe said. The number of obese people in Western countries has almost tripled since 1975. In the USA, 40% of people are overweight and 30% are obese.

For the years 1998 to 2010, the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) compared the BMI of a cohort of HIV-infected NA-ACCORD members with matched controls from the United States National Health and Nutrition Examination Survey (NHANES). In NA-ACCORD between 1998 and 2010, the median BMI at the beginning of antiretroviral therapy (ART) increased from 23.8 to 24.8 kg/m2, but the percentage of obese increased from 9% to 18%. After 3 years of ART, 22% of the normal-weight patients had become overweight, 18% of the overweight patients were obese. More than 80% of weight gain over 3 years occurred in the first 12 months of ART. Weight gain was highest in white men and not white women. After 3 years of ART, the BMI reached the value corresponding to the age, sex, and race of the US general population.

Social and geographical factors

The increase in BMI is promoted by changes in dietary habits and lifestyle factors and overlaps in epidemics such as HIV and obesity. There are also HIV-specific factors such as earlier diagnosis and treatment, closer care with access to other resources such as nutritional support, smoking cessation or psychological support.

"People with HIV are getting heavier because this is a national and international health trend," says Koethe. "However, there is a remarkable geographical overlap between obesity and HIV in the US, as well as other diseases such as diabetes prevalence or death from heart disease and stroke. A further geographical overlap of obesity results from the prevalence of poverty.

Weight gain in HIV patients under ART is therefore multifactorial. It is partly due to reduced inflammation and catabolism after viral suppression, better access to care facilities and treatment of depression.

HIV and obesity act synergistically

As in the normal population, higher body weight is also associated with a higher risk of secondary diseases in HIV-infected persons. However, the risk and incidence of diabetes in HIV patients increase much more with increasing body weight than in HIV-negative individuals.

There are similar findings for neurocognitive deficits, fatty liver, cardiovascular events, and multimorbidity. HIV and obesity, therefore, appear to act synergistically as risk factors. This could be explained by the fact that HIV infection and obesity have similar effects on fat metabolism. They are both characterized by an energy excess status, which is mainly due to increased lipid production in the liver, but also to reduced lipid storage and increased fat release from the fatty tissue. There is an increase in fat deposits in the liver, muscle, and heart. The ectopic deposition of fat occurs in HIV-infected persons at a lower BMI and at a younger age than in HIV-negative persons. It increases with increasing body weight.

Current studies in ART-naive patients

In the ACTG-A5257 study, 1,809 ART-naive HIV patients under tenofovir disoproxil fumarate/emtricitabine were treated openly and randomly with atazanavir/ritonavir, darunavir/ritonavir or raltegravir for at least 96 weeks. A recent evaluation of the body weight study showed that participants had gained an average of 3.8 kg over 96 weeks, 21% more than 10% heavier. The waist circumference had increased by 3.4 cm in the same period. The risk of weight gain and increased waist circumference was significantly greater with raltegravir treatment. The increase was highest in women and black patients.

An analysis of the NA-ACCORD data from Bourgi et al. presented at CROI 2019 showed that weight gain was highest in patients with integrase inhibitors, especially dolutegravir and raltegravir. After 2 and 5 years they had gained 4.9 and 6.0 kg, respectively, and under NNRTI the weight gain was 3.3 and 4.3 kg, respectively. Among protease inhibitors, the weight gain was 4.4 kg and 5.1 kg respectively. However, the data are collected retrospectively.

Current studies on the change of ART

One of the first studies on this topic came from the Italian SCOLTA cohort in 2017 and analyzed the data of 1,118 patients who had switched to an integrase inhibitor (INI), darunavir or rilpivirine, mainly due to the failure of protease inhibitor therapy. Body weight increased in all patients switching to a new regime, with higher age, lower BMI and low CD4 levels associated with higher weight gain.

A retrospective study with 495 participants showed that body weight increases when switching from an efavirenz-based regime to an INI-based therapy. The strongest increase was in patients switching to dolutegravir.

Another analysis presented at CROI 2019 had 972 participants in A5001 and A5322 after switching to integrase inhibitors. It showed that women, people with black skin, and patients over 60 years of age had the highest gain and that dolutegravir was associated with the highest weight gain.

The studies show that therapy with integrase inhibitors leads to a significant increase in weight, although this effect varies between the individual substances. Koethe emphasized: "There is a high need for prospective studies and pooled analyses from randomized clinical trials before conclusions can be drawn.''

Koethe JR. Obesity: a growing problem in antiretroviral therapy. CROI 2019, Seattle, Washington, March 7, 209, Abstract 158. http://www.croiconference.org/sessions/obesity-growing-problem-antiretroviral-therapy

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