Starting HIV treatment reduces risk of kidney disease

Michael Carter
Published: 23 August 2012

Starting HIV treatment reduces the risk of chronic kidney disease, US investigators report in the online edition of AIDS. This was especially the case for patients who experienced robust increases in their CD4 cell count and falls in their viral load.

However, the study also showed that initial therapy that included tenofovir (Viread, also in Truvada, Atripla and Eviplera) and a ritonavir-boosted protease inhibitor was associated with a decline in kidney function. Nevertheless, the investigators stress that its incidence was rare, involving no more than 6% of patients taking this regimen over four years of follow-up.

“Effective ART [antiretroviral therapy]…lowered the risk of CKD [chronic kidney disease],” write the authors.

Kidney disease is an important cause of serious illness in patients with HIV. The exact causes are controversial, but seem to include traditional risk factors such as high blood pressure, the inflammatory effects of untreated HIV infection and the side-effects of some antiretroviral drugs.

The anti-HIV drugs most associated with the development of chronic kidney disease are the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir and ritonavir-boosted protease inhibitors.

US researchers wanted to establish a clearer understanding of the impact of starting antiretroviral therapy on the risk of kidney disease. They also wished to see if combinations of specific anti-HIV drugs were associated with an increased risk of decline in kidney function.

They therefore designed an observational study involving 3329 patients who started HIV therapy between 1996 and 2009. Moderate chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) below  60 ml/min/1.73m2 and serious disease as an eGFR below 30 ml/min/1.73m2.

The patients were followed for a median of five years. This median duration of follow-up before the initiation of HIV therapy was approximately six months.

Two-thirds of patients remained on their initial treatment combination throughout the study. This included 83% of individuals taking tenofovir and 73% of those treated with a ritonavir-boosted protease inhibitor.

Moderate chronic kidney disease was rare, developing in a total of 106 patients a median of 45 weeks after starting antiretroviral therapy. This provided an incidence of 10 cases per 1000 person years of follow-up.

Factors associated with moderate kidney disease were black race, co-infection with hepatitis C virus, high blood pressure requiring therapy, a previous AIDS-defining illness, a low nadir and current CD4 cell count and a higher current viral load. No antiretroviral combination was associated with the emergence of chronic kidney dysfunction in this initial model.

In all, a total of 72 patients developed kidney disease when taking their initial combination of antiretroviral drugs. Those patients whose initial regimen included tenofovir and ritonavir were significantly more likely to meet the criteria for chronic kidney disease than those taking an alternative regimen (p = 0.006).

However, there was no significant association between regimens including tenofovir and a ritonavir-boosted protease inhibitor when the investigators used a more stringent definition of moderate chronic kidney disease (eGFR below 45 ml/min/1.73m2). Nor was this combination of drugs associated with a risk of severe kidney dysfunction. Factors associated with both these outcomes included black race, hepatitis C co-infection and CD4 cell count and viral load.

“We observed a significantly slower rate of eGFR decline in association with treatment with ART,” comment the investigators. They emphasise that even though initial regimens containing tenofovir and a ritonavir-boosted protease inhibitor were associated with moderate kidney disease, its incidence was low.

“These findings suggest durable benefits of ART-associated immunologic and virologic improvements in reducing the risk of kidney disease, while delineating contributions by ART-specific toxicities, demographic factors and comorbidities to this important complication.”

Reference

Kalayjian RC et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. AIDS 26, online edition. DOI: 10.1097/QAD.0b013e328357f5ed, 2012.