"The kidneys are one of the most frequently affected sites of infection in individuals with HIV." - 8
When we think of HIV, we typically focus on its devastating impact on the immune system. Yet, this complex virus affects far more than just CD4 cells. For decades, doctors have recognized that the kidneys are particularly vulnerable to HIV-related damage, with potentially serious consequences for health and survival 7 .
Average prevalence of kidney dysfunction in HIV patients in Africa 8
Increased odds of HIVAN with APOL1 risk variants 1
HIV-associated nephropathy (HIVAN) emerged as a major concern, particularly affecting people of African descent and often progressing rapidly to kidney failure 1 .
HIV-associated nephropathy, or HIVAN, represents the most classic form of HIV-related kidney disease. It's defined by a distinct pattern of injury visible under the microscope: a collapsing form of focal segmental glomerulosclerosis accompanied by significant tubulointerstitial damage 1 3 .
In HIVAN, the virus triggers a destructive process primarily targeting the kidney's filtering units:
Unlike its attack on immune cells, HIV employs different tactics to damage kidney tissue:
HIVAN doesn't affect all populations equally. Its distribution reveals fascinating patterns that underscore the role of genetics in disease susceptibility.
Groundbreaking research has identified a powerful genetic link to HIVAN through variations in the APOL1 gene 1 . These genetic variants, found almost exclusively in people of African descent, originally evolved to provide protection against African sleeping sickness but inadvertently increase susceptibility to certain kidney diseases 1 .
Individuals possessing two APOL1 risk alleles have an 89-fold increased odds of developing HIVAN compared to HIV-positive controls without these variants 1 .
| Region | Prevalence of Kidney Dysfunction | Notes |
|---|---|---|
| Africa | 16.85% (pooled average) 8 | Ranges from 5.5% in South Africa to 38% in Nigeria 1 |
| Ethiopia | 18.10% 4 | Based on systematic review of 12 studies |
| Zambia | 10.7% 2 | Among adults on antiretroviral therapy |
| North America | 4.7%-9.7% 1 | When defined as eGFR <60 mL/min/1.73 m² |
| Europe | 4.8% 8 | Based on CKD-EPI equation |
Patients with HIVAN typically present with distinctive features 1 7 :
Diagnosing HIV-related kidney disease involves multiple approaches 7 :
| Condition | Key Distinguishing Features |
|---|---|
| Classic HIVAN | Collapsing FSGS on biopsy, high viral load, low CD4 count 7 |
| ART-induced nephropathy | Indolent course, lower proteinuria, better immune status 7 |
| HIV-associated immune complex disease | Various immune complex deposits on biopsy 7 |
| Diabetic nephropathy | Clinical history of diabetes, characteristic biopsy findings 1 |
| Hypertensive nephrosclerosis | Long-standing hypertension, retinal changes 1 |
Managing HIV-related kidney disease requires a multi-pronged approach:
Combination antiretroviral therapy (cART) forms the cornerstone of HIVAN treatment 7 . Effective viral suppression can prevent and even reverse some aspects of HIVAN.
Research from Zambia demonstrates that implementation of the "test-and-treat" policy—where ART is initiated immediately upon diagnosis—was associated with lower odds of kidney function impairment compared to earlier treatment approaches .
A 2025 study from Zambia found that older age and use of dolutegravir with TDF/3TC regimens were positively associated with kidney impairment 2 . This underscores the need for careful monitoring, especially in vulnerable populations.
Research presented at the 2025 International AIDS Society Conference revealed that hepatitis B co-infection significantly increases kidney risks for people living with HIV. The rate of kidney dysfunction nearly doubled (14.9% vs. 8%) in those with both HIV and HBV compared to HIV alone 6 .
The 2025 IAS Conference spotlighted progress in long-acting HIV solutions, including newly approved injectable medications and once-monthly oral pills in advanced trials 9 . These innovations could improve adherence and potentially indirectly benefit kidney outcomes.
| Risk Factor | Impact on Kidney Dysfunction Risk |
|---|---|
| Older age (≥50 years) | 8.94-fold increased odds 8 |
| APOL1 risk variants | 89-fold increased odds of HIVAN 1 |
| Hepatitis B co-infection | Nearly doubles rate of kidney dysfunction 6 |
| Low CD4 count (<200 cells/mm³) | 3.64-fold increased odds 8 |
| Diabetes mellitus | 2.84-fold increased odds 8 |
| Female sex | 1.82-fold increased odds 8 |
| Obesity (BMI ≥30 kg/m²) | 4.70-fold increased odds 8 |
Kidney impairment remains a significant concern for people living with HIV, even in the era of effective antiretroviral therapy. While the terrifyingly rapid progression of classic HIVAN has become less common with early treatment initiation, new challenges have emerged—including drug-related toxicity and kidney aging in an increasingly older HIV population.
The key to protecting kidney health lies in consistent assessment of kidney function through blood and urine tests.
Treatment choices should consider individual risk factors, including genetics, age, and comorbidities.
Managing traditional risk factors like hypertension and diabetes is crucial for kidney protection.
APOL1 variant testing may eventually enable more targeted screening and prevention strategies.
The dramatic decline in HIVAN incidence since the advent of combination ART delivers a powerful message: effective HIV treatment is itself kidney-protective. With continued research, improved medications, and vigilant care, the goal remains ensuring that people living with HIV can not longer lives but healthier ones, with their kidneys functioning optimally for decades to come.