Renal Trajectories Across Histopathological Phenotypes in Treated HIV: A Multicenter Biopsy-Based Observational Study.

BACKGROUND

Despite widespread antiretroviral therapy (ART), kidney disease in people living with HIV remains clinically and biologically heterogeneous. Persistent immune imbalance-reflected by CD4/CD8 inversion-often coexists with virologic suppression, yet its relevance within biopsy-defined renal phenotypes is incompletely understood. We aimed to characterize clinicopathological phenotypes and longitudinal renal trajectories in treated people living with HIV using the KDIGO histopathological framework.

METHODS

We conducted a retrospective multicenter cohort study of PLWH undergoing native kidney biopsy in Mexico (2019-2025) with ≥6 months of follow-up. Biopsies were classified according to the KDIGO proposal. Renal trajectory was defined as >25% decline (progression), ≤25% change (stabilization), or >25% increase (improvement) in creatinine-based estimated glomerular filtration rate (eGFR). Immunologic parameters, histological chronicity indices, and kidney outcomes were analyzed descriptively.

RESULTS

Thirty-eight patients were included (87% men; median age 43 years). Late HIV diagnosis was frequent (47% with CD4+ <200 cells/µL). At biopsy, 92% were receiving ART; however, CD4/CD8 inversion persisted in 84% at baseline and 76% at follow-up despite significant CD4+ recovery (p<0.01). After a median follow-up of 15 [8-18] months, 24% developed kidney disease progression, whereas 76% showed stabilization or improvement. Baseline albuminuria was significantly higher among progressors (3,589 vs. 339 mg/g; p=0.01), while CD4/CD8 ratio was not associated with short-term progression. Immune complex disease presented earlier after HIV diagnosis and showed immunologic improvement (CD4+ p=0.01; CD4/CD8 p<0.01) with stable renal function. Podocytopathies exhibited greater structural chronicity, and tubulointerstitial disease was frequently associated with opportunistic infections, particularly disseminated mycobacterial disease.

CONCLUSIONS

In treated HIV infection, renal disease follows phenotype-specific trajectories in the context of persistent immune imbalance despite viral suppression. Albuminuria, rather than systemic immune indices, identified patients at higher short-term risk of progression. Biopsy-guided classification identified distinct clinicopathological phenotypes with different renal trajectories and may support individualized HIV-nephrology care in resource-constrained settings.