HIV, ARVs and kidney impairment

People with HIV may develop a condition called HIV-associated nephropathy (HIVAN), a syndrome causing loss of protein through the urine and decreasing renal (kidney) function. HIVAN is common in people with advanced HIV disease, but usually improves after starting effective antiretroviral therapy.¹ 

Some antiretrovirals in themselves cause kidney problems and are described as nephrotoxic. Definitions and criteria for a diagnosis of acute renal failure vary, making it difficult to gauge incidence in general, or with the added complications of HIV disease and antiretroviral drug use.

However, a recent study that followed over 600 patients for several years has concluded that although ART can slow down kidney function decline (defined as glomerular filtration rate estimated from serum creatinine [eGFR]), loss of kidney function continues slowly, even with durable viral suppression. This can be attributed to traditional kidney disease risk factors (e.g. high blood pressure), intermittent viraemia, and nephrotoxicity associated with some antiretrovirals. CD4 cell count was not predictive of declining kidney function.²

Similarly, kidney function remained almost constant over seven years in a French cohort of over 1000 HIV patients. The average GFR and the percentage of patients with impaired GFR (below 60 ml/min/1.73m²) remained essentially unchanged over the study period, Neither tenofovir nor any other antiretroviral drug was significantly associated with the poorer evolution of GFR after 16 months of HIV therapy.³

In a London-based retrospective analysis of HIV patients, nearly 6% of patients developed acute renal failure (ARF). CD4 nadir and AIDS diagnosis were associated with ARF in the first three months of antiretroviral therapy and there were over 19 episodes per 100 person-years. After three months of therapy, just one episode of ARF was found per 100 person-years and this was associated with CD4 nadir, injection drug use, and hepatitis C co-infection. In this population, ARF was associated with advanced immunodeficiency and incidence decreased remarkably after receiving antiretroviral therapy.⁴

Africa has a high burden of both renal disease and HIV. In Zambia, nearly 33% of the 26,000 persons initiating antiretroviral therapy between 2004 and 2007 in Zambia had renal disease at baseline. The adjusted hazard ratio for mortality (adjusted by baseline CD4 count, WHO HIV stage, haemoglobin, and adherence) in those with mild and moderate disease was twice that of those individuals without renal disease at baseline. Patients with severe renal disease at baseline had a fivefold increased risk of mortality as compared to those without renal disease. This points to the need to include simple screening and treatment algorithms for renal disease in antiretroviral treatment programmes, particularly in settings where tenofovir use is widespread.⁵  

Suppression of viral load was associated with improved renal function in those who began antiretroviral therapy with low CD4 cell counts and grade 2 or higher kidney disease in a subset of participants enrolled in US AIDS Clinical Trial Group studies. This finding indicates, as have other studies, that viral replication contributes to chronic renal dysfunction in advanced HIV.⁶