Renal Trajectories Across Histopathological Phenotypes in Treated HIV

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.