Natural History of HIVAN
Without treatment, HIVAN progresses rapidly to end-stage renal disease within weeks to months, making it one of the most aggressive forms of kidney disease. 1, 2
Untreated Disease Course
The natural progression of HIVAN in the pre-HAART era was uniformly devastating:
- Rapid progression to ESRD occurs within 3.9 months on average without antiretroviral therapy, compared to 18.4 months with treatment 1
- All untreated patients in observational studies progressed to ESRD, with 100% of patients not receiving ACE inhibitors reaching end-stage disease (146.5 days median survival) 3
- The disease typically manifests in patients with advanced HIV infection, with the majority having an AIDS-defining condition at diagnosis 2
- Patients present with high-grade proteinuria (often nephrotic range) and enlarged kidneys on ultrasonography 4
Clinical Presentation Context
HIVAN occurs predominantly in specific populations:
- The disease affects almost exclusively Black patients between ages 20-64, representing the third leading cause of ESRD in this demographic 2, 5
- HIVAN is strongly associated with low CD4+ cell counts and typically occurs in the setting of severe immunosuppression 1
- The disease is mediated by direct HIV infection of renal epithelial cells with active viral replication within kidney tissue 5
- APOL1 high-risk genotypes (G1 and G2 variants) confer genetic susceptibility, though a "second-hit" event is required for disease manifestation 1, 6
Impact of Antiretroviral Therapy on Disease Course
The introduction of HAART has fundamentally altered HIVAN's natural history:
- HAART dramatically slows GFR decline from 4.3 mL/min/month to 0.08 mL/min/month 1
- Treatment prolongs time to ESRD and increases overall renal survival from 12.5% to 18.1% 1
- HAART can reverse established renal failure, with case reports documenting complete recovery of renal function after treatment initiation 4
- The incidence of new HIVAN cases has decreased substantially in the HAART era, with only 1 case identified among 23 patients with HIV RNA <400 copies/mL versus 23 cases among 63 patients with HIV RNA ≥400 copies/mL 1
Evolution of Histopathology
The pathologic course shows distinct patterns:
- Classic HIVAN presents with collapsing glomerulopathy, tubular microcyst formation, interstitial inflammation, and diffuse podocyte foot process effacement 1
- Sequential biopsies demonstrate evolution from collapsing glomerulopathy to non-collapsing FSGS (NOS) in some cases 1
- In the HAART era, non-collapsing FSGS is more commonly encountered at biopsy, with viral loads often undetectable and less severe podocyte effacement 1
- Late-stage disease shows sclerotic tufts retracted into tight solid spheres resembling "fetal glomeruli" 1
Critical Prognostic Factors
Several factors influence disease trajectory:
- Achieving HIV RNA suppression to <200 copies/mL with ART is associated with improved outcomes, though one study showed no difference in 3-month ESRD progression rates 1
- Early initiation of ACE inhibitors appears most effective when administered early in the disease course 3, 2
- Protease inhibitor-based regimens showed greater renal benefit compared to nucleoside analogues alone 3
- Up to 50% of HIV-positive patients with glomerular disease have lesions other than classic HIVAN, emphasizing the importance of biopsy for accurate diagnosis and prognosis 3
Contemporary Disease Course
In the modern treatment era:
- Earlier ART initiation guidelines may further reduce HIVAN incidence, though the overall risk-benefit for kidney health remains incompletely defined 1
- HIV-associated FSGS (non-collapsing) is now associated with higher CD4+ counts and occurs in patients already receiving ART 1
- Patients with HIVAN receiving HAART and dialysis achieve survival rates comparable to dialysis patients without HIV infection 1
- Renal transplantation is feasible in selected HIV-positive patients with similar patient and graft survival to non-infected recipients, though with higher rejection rates 3