HIV, Nephrotoxic Medications, and Chronic Kidney Disease: Prevalence, Risk Factors, and Mediation Analyses Among People With and Without HIV Enrolled in the Multicenter AIDS Cohort Study (MACS) / Women’s Interagency HIV Study (WIHS) Combined Cohort Study

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Background: Chronic kidney disease (CKD) affects over 37 million adults in the United States, and people living with HIV (PLWH) are at greater risk for progression to end-stage kidney disease. Although both conditions are common among PLWH, the potential pathways through which depression and use of medications with nephrotoxic potential may influence CKD development remain underexplored. We evaluated the relationships of depression and nephrotoxic medication use with CKD prevalence among PLWH, and investigated the potential mediating effects of these factors on the pathway to CKD among PLWH. Methods: ) and its association with HIV serostatus. Generalized Estimating Equations (GEE) with a Poisson distribution and log link were used to estimate relative risks (RR) for CKD associated with HIV, depression, and other covariates. Counterfactual-based causal mediation analysis was conducted to assess whether depressive symptoms or nephrotoxic medication use partially explained the observed association between HIV and CKD. Results: Among 2,530 participants [1,622 PLWH and 908 people living without HIV (PLWoH)], CKD prevalence was higher in PLWH (18.1%) compared to PLWoH (9.7%). GEE analysis revealed that HIV serostatus was significantly associated with an increased risk of CKD (RR = 1.37, 95% CI: 1.28-1.48, p < 0.0001). Other significant factors included age (RR = 1.03, 95% CI: 1.03-1.03, p < 0.0001), non-Hispanic Black (RR = 1.19, 95% CI: 1.11-1.27, p < 0.0001) compared to non-Hispanic White, diabetes (RR = 1.26, 95% CI: 1.17-1.35, p < 0.0001), and higher income (RR = 0.99, 95% CI: 0.98-1.00, p = 0.005). Mediation analysis indicated that nephrotoxic medication use, accounted for a small but significant proportion of the HIV- CKD association (indirect effect OR = 1.02, 95% CI: 1.00-1.03, p = 0.02). Conclusions: While it is well established that PLWH have a higher prevalence of CKD compared to PLWoH, our findings suggest that nephrotoxic medication use may modestly amplify this risk. Although most of the risk appears to be attributable to the direct effects of HIV, these medications represent a modifiable contributor. PLWH receiving such treatments may benefit from closer kidney function monitoring. Future research should investigate additional psychosocial and behavioral contributors to CKD among PLWH, including depression.

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