Patients taking HIV treatment need to maintain undetectable viral load to protect kidney function

Kidney function declines in patients taking antiretroviral therapy if their viral load is not fully suppressed, US investigators report in a study published in the online edition of AIDS. Although kidney function improved once a patient started taking HIV treatment, continued declines were observed in some patients, especially if their viral load “blipped” to detectable levels.

“We found that untreated poorly controlled HIV infection was associated with ongoing loss of kidney function and that the provision of antiretroviral therapy had a beneficial effect over time”, comment the investigators.

Thanks to antiretroviral therapy, the prognosis of HIV-positive patients is now considered to be normal. However, kidney disease has become an important cause of illness in patients with HIV, and its prevalence is expected to increase as the HIV-positive population ages.

The causes of kidney disease in patients with HIV are not yet fully understand, but it has been suggested that a high viral load, low CD4 cell count and the side-effects of some anti-HIV drugs may all be important.

US investigators therefore conducted a study to try and identify the factors associated with the loss of kidney function in a cohort of HIV-positive patients. Because kidney disease in patients with HIV may be due to a complex interaction between CD4 cell count, viral load and the use of antiretroviral therapy, the study included a small number of patients who maintained an undetectable or very low viral load (below 500 copies/ml) without the need for antiretroviral therapy. The investigators theorised that these patients would not have the immune deficiency, ongoing HIV replication, and exposure to antiretroviral drugs that are potential risk factors for kidney dysfunction.

Kidney function was assessed using estimated glomerular filtration rate obtained from serum creatinine.

A total of 615 patients were included in the study. The mean age was 45 years and 87% were men. Half of the participants were white, 29% black and 10% Hispanic. Risk factors for kidney disease, including infection with hepatitis C virus and high blood pressure were present in 15% of patients.

In 45 patients (7%) viral load was controlled without the need for antiretroviral therapy. HIV treatment resulted in the control of HIV replication in a further 173 individuals (20%).

During the three years of the study, the investigators analysed over 9000 creatinine measures and the overall estimated glomerular filtration rate declined by – 2.6 ml/min per 1.73m³ per year.

Factors significantly associated with worsening kidney function were female sex (p = 0.004), diabetes (p = 0.02) and high blood lipids (p = 0.008). No association was identified between CD4 cell count or viral load and kidney function.

To assess the rate of antiretroviral treatment on kidney function the investigators monitored estimated glomerular filtration rate in 82 individuals starting HIV treatment for the first time. The investigators analysed kidney function tests before and after the patients initiated antiretroviral therapy.

In the period before HIV treatment was started, the average glomerular filtration rate decline was – 4.7 ml/min per 1.73 m². Although kidney function still declined after antiretroviral therapy was started, the rate slowed to – 1.9 ml/min per 1.73 kg². This meant that taking anti-HIV drugs was associated with a + 2.8 ml/min per 1.73 m² improvement in the estimated glomerular filtration rate slope.

Next the investigators compared kidney function between the patients taking HIV treatment who had a viral load below 500 copies/ml with that of individuals who had a viral load below this level without the need for anti-HIV drugs.

The difference in the loss of kidney function was – 4.4 ml/min per 1.73m² in treated vs. untreated viral controllers.

Blips in viral load were strongly associated with loss of kidney function in the patients taking HIV treatment ( - 6.9 ml/min per 1.73 m²).

Traditional risk factors for kidney disease such as high blood pressure ( - 4 ml/min per 1.73 m² and diabetes ( - 5.6 ml/min per 1.73 m²) were also associated with loss of kidney function in patients taking HIV treatment with a low viral load. CD4 cell count, however, was not predictive of the loss of kidney function.

“These findings suggest that antiretroviral therapy is beneficial to kidney function, but fully suppressive treatment may be needed to curb estimated glomerular filtration rate decline”, write the investigators.

They believe that this is because “HIV directly infects all cell types in the kidney and actively replicates there in a wide variety of patients”.

The investigators recommend that additional studies should be undertaken “to identify HIV infected persons who may be susceptible to declines in kidney function as a result of antiretroviral therapy and to determine whether declines in kidney function are related to complications of treatment, such as diabetes or hypertension, or nephrototoxicity associated with the drugs themselves.”