Diabetes, hypertension and dyslipidemia raise kidney disease risk in people with HIV

People with HIV develop chronic kidney disease at more than twice the rate of people without HIV, and modifiable risk factors such as hypertension, diabetes and dyslipidemia appear to shape that risk, according to a large cohort study conducted within the Kaiser Permanente integrated health care system. The research, published as an open-access article in AIDS Research and Therapy, also found that tenofovir use was associated with a lower adjusted risk of incident kidney disease among people with HIV, with protection that was significantly greater for tenofovir alafenamide than for tenofovir disoproxil fumarate.

The study set out to address a gap the authors describe in the background of the paper: the association of modifiable risk factors with incident chronic kidney disease among people both with and without HIV, including alcohol use disorder, diabetes, dyslipidemia, hypertension, smoking, and potentially tenofovir in its alafenamide and disoproxil fumarate forms, is not well established. To examine these relationships, the researchers identified adults with HIV and adults without HIV, frequency matched at a ratio of one to twenty, within Kaiser Permanente from 2000 through 2023.

Participants were followed until they experienced incident chronic kidney disease, defined as an estimated glomerular filtration rate below 60 ml/min/1.73m2 based on at least two measures taken at least 90 days apart, or until disenrollment, death, or the end of the observation period on December 31, 2023. The primary predictors were the risk factors listed above, and the analyses were adjusted for demographic and clinical covariates extracted from electronic health records.

The overall cohort was 87 percent male, 35 percent non-Hispanic White, 24 percent Black, and 24 percent Hispanic. Over the follow-up period, there were 5,516 incident chronic kidney disease events among people with HIV and 41,899 such events among people without HIV. The corresponding rates were 1.99 and 0.75 per 100 person-years, yielding an adjusted rate ratio of 2.52, which was statistically significant with a p value below 0.001.

Among people with HIV, hypertension, diabetes and dyslipidemia were each significantly associated with a higher risk of developing chronic kidney disease, while alcohol use was associated with a lower risk. Notably, the traditional risk factors for chronic kidney disease were not as strongly associated with the outcome among people with HIV as they were among people without HIV, a difference that was itself statistically significant across the comparisons, with all p values below 0.001.

The findings on antiretroviral therapy were also striking. Among people with HIV, tenofovir use overall was associated with a lower adjusted risk of chronic kidney disease, and the protective association was significantly higher with tenofovir alafenamide compared with tenofovir disoproxil fumarate.

The authors conclude that modifiable risk factors impact the associated risk of chronic kidney disease among people with HIV, especially in comparison with people without HIV. In their view, improved renal health requires hypertension, lipid, and diabetes control, along with the use of tenofovir alafenamide. Because these are modifiable conditions, the results suggest that attention to cardiovascular and metabolic risk factors may also carry benefits for kidney health in this population.

Several caveats are worth keeping in mind when interpreting the study. It was conducted within a single integrated care system in the United States, and the article was shared early as a peer-reviewed, accepted manuscript that is subject to further edits before the final version of record. As an observational cohort study, the reported associations, including the apparent protective association of tenofovir alafenamide and the lower risk seen with alcohol use, describe relationships in the data rather than demonstrated causal effects, and residual confounding cannot be excluded. The adjusted analyses accounted for demographic and clinical covariates from electronic health records, but the authors’ conclusions about what improved renal health requires reflect the associations observed in this cohort rather than results from a randomized intervention.

Within those limits, the study adds a substantial body of evidence on kidney disease risk in the modern treatment era, drawing on more than two decades of data and tens of thousands of incident chronic kidney disease events. It highlights that people with HIV continue to experience kidney disease at markedly higher rates than people without HIV, that the familiar modifiable risk factors remain important in this population, and that the choice between tenofovir formulations may be associated with meaningful differences in adjusted kidney disease risk.

Subject of Research: Modifiable risk factors, tenofovir use and incident chronic kidney disease in people with and without HIV

Article Title: Modifiable risk factors, tenofovir use and incident chronic kidney disease among people with HIV and people without HIV

Article References: Horberg, M., Hu, H., Lam, J. O., Lea, A. N., Fan, D., Lopez, E., Deneal, A. N., Towner, W., & Silverberg, M. J. (2026). Modifiable risk factors, tenofovir use and incident chronic kidney disease among people with HIV and people without HIV. AIDS Research and Therapy. https://doi.org/10.1186/s12981-026-00941-x

Image Credits: AI Generated

DOI: 10.1186/s12981-026-00941-x

Keywords: HIV, chronic kidney disease, tenofovir alafenamide, tenofovir disoproxil fumarate, hypertension, diabetes, dyslipidemia, eGFR, Kaiser Permanente, cohort study, kidney disease risk, antiretroviral therapy