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Does Living Environment Affect Health Outcomes of People Living with HIV?

Does Living Environment Affect Health Outcomes of People Living with HIV?

Investigating how diet impacts the microbiome of Africans living with HIV starts with collecting data. CU data researcher Cathy Lozupone, PhD, explains recent findings in urban and rural patients and what they mean for future research.

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Written by Kara Mason on March 8, 2024

Cathy Lozupone, PhD, professor of biomedical informatics at the University of Colorado School of Medicine, and the researchers in her lab are interested in the microbiomes of HIV patients.

Typically, the lab focuses their efforts on patients in the Denver-metro region, but in a new study, the researchers turn their attention to HIV patients in Zimbabwe and whether living in an urban or rural setting impacts immune and microbiome responses to antiretroviral therapy (ART).

The research, published in the journal Microbiome, originally started with a question of whether having a high-fiber, low-fat "agrarian-type" diet would show improved health outcomes for HIV infected individuals undergoing ART. Lozupone says her lab took on this question because other researchers previously investigated a simian immunodeficiency virus (SIV)-infected mouse model that had shown more severe disease with a high-fat, low-fiber diet.

However, Lozupone and her colleagues quickly realized that many factors may be at play — other than diet — resulting in urban HIV patients, who were on average consuming a more Western-type diet, having more pronounced improvements with ART compared to rural HIV patients consuming, on average, a more agrarian-type diet. In the rural group, researchers observed reductions in inflammatory markers and T-cell activation and exhaustion, which are hallmarks of disease progression and associated comorbidities in controlled infection.

While ART has dramatically improved health outcomes in people living with HIV, ART coverage remains suboptimal in many parts of the developing world, including sub-Saharan Africa where about 70% of the global HIV epidemic is concentrated. Rural areas face especially steep challenges.

“Even with successful ART, people living with HIV often have chronic immune activation and elevated inflammation that has been linked with poor CD4+T cell recovery and the premature onset of HIV-related comorbidities, such as heart disease and age-associated frailty,” Lozupone says. “Understanding factors related to chronic immune activation with ART is essential for devising strategies to protect the health of people living with HIV.”

Following the data

The researchers analyzed 162 individuals, half from the Mabvuku Polyclinic in the city of Harare and half from the Mutoko District Hospital that services rural villages outside of Harare. Their research found that immune improvements with ART were much more significant in the urban group. Additionally, gut microbiome composition showed specific relationships with the amount of immune activation and exhaustion markers measured in blood, and differed between individuals residing in urban and rural areas.

“We saw that people in the rural areas were not responding as well to therapies, immune exhaustion was maintaining, and we had a high demographic of underweight people living with HIV — that was surprisingly observed in people on ART but not with untreated infection,” Lozupone says.

The stigma around being HIV positive is still high in many places in Africa and can lead to unemployment and food insecurity. This was a bigger factor than Lozupone says she initially anticipated. Inflation and urban food insecurity may also play a role in diet.

While this study focuses only on the specific differences found in the urban and rural groups, it does raise many more questions about potential reasons for the results. For example, it's standard of care across Africa to prescribe an antibiotic with ART to prevent infection. This may play some role in the gut microbiome and overall immune response.

This research is the first paper looking at the data collected from the cohort. The lab plans to publish more.

What’s next for the diet question

Lozupone’s lab plans to complete further analysis on their findings from the urban and rural participants. Some of that work will dive further into the original diet question and how other variables may impact it, she says.

“It can be more difficult for the patients in rural settings to get to a clinic and access necessary drugs, and while there has been movement in trying to get more and better treatments to these people, our work is showing that these patients have suppressed virus indicating they’re getting the drug, but not the immune improvements that they should,” Lozupone says.

“If we can figure out why that is, whether it’s diet or something else, then you can start moving into how to provide these people living with HIV with what’s missing to improve ART responses and prevent poor health outcomes,” she continues.  

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Catherine Lozupone, PhD