HIV-Related Immune Activation May Predict Weight Gain and Exacerbate Complications, Especially in Women

Cross-posted from NIAID Now Blog

Consistently taking antiretroviral therapy (ART) as prescribed allows men and women with HIV to live long, healthy lives and prevent transmitting HIV to sexual partners. Yet even when the virus is well-controlled with ART, HIV can cause persistent immune activation that contributes to an increased risk of complications such as heart disease and certain cancers. New NIAID-supported research presented today [March 6] at the Conference on Retroviruses and Opportunistic Infections in Seattle sheds light on the relationship between immune activation and weight gain.

Investigators found that, among a selected group of 340 men and women with HIV, those who gained weight after beginning ART had higher levels of immune activation at the start of the study than those who maintained their weight. Women who gained weight were at a greater risk of having high immune activation levels even after taking ART, shedding light on sex-related disparities seen in certain HIV comorbidities.

Researchers at the University of Nebraska Medical Center, Harvard T.H. Chan School of Public Health, Case Western Reserve University School of Medicine, and NIAID analyzed data from selected groups of men and women who either gained or maintained weight during two completed clinical trials conducted by the AIDS Clinical Trials GroupExit Disclaimer—A5202 and A5257—testing regimens of antiretroviral drugs. Investigators then compared levels of several proteins associated with immune activation in each group at the start of the trials, when their HIV was untreated, to levels after 96 weeks on treatment.

For both men and women, weight gain was more likely in volunteers who started ART with high levels of immune activation. While effective ART suppressed HIV and brought down levels of immune activation in all groups, the reduction was not as robust in women who had gained weight. These findings suggest that HIV-related weight gain and immune activation may amplify each other, especially in women. Developing and refining strategies to help people with HIV maintain a healthy weight as well as interventions that reduce underlying immune activation, the presenters suggest, may help minimize complications from HIV.

On average, the participants in this analysis had body mass indexes, or BMIs—ratios of weight to height used to estimate a person’s body composition—that fell in a normal range both before and after beginning ART. None of the volunteers included in this analysis were considered underweight, and on average, those who gained weight gained about 6 to 14 pounds. Though uncontrolled HIV was widely associated with opportunistic infections and life-threatening weight loss, or wasting, in the past, people with HIV in developed countries are now more likely than those without HIV to be overweight or obese. This shift has led more researchers to examine the interactions between HIV and weight gain and interventions that may specifically help people with HIV maintain a healthy weight and avoid noninfectious complications like heart disease and cancer.

Reference: S. Bares et al. The impact of weight gain and sex on immune activation following initiation of ART.  Conference on Retroviruses and Opportunistic Infections, Seattle 2019.