Kidney function deteriorates more rapidly in older people with HIV than in age-matched controls in both untreated and treated people, suggesting that antiretroviral therapy should be started soon after diagnosis with HIV to protect kidney function, according to UK research presented to the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur.
People with HIV over 70 years of age were at especially high risk of kidney failure, but the risk was also elevated in the over-50s.
Improvements in HIV treatment and care and a high rate of new infections mean that an ever-increasing proportion of HIV-positive people are aged 50 and over. As a result, the diseases of ageing are an increasingly important cause of serious illness and death in people with HIV.
It is well known that kidney function declines with age. An increased risk of renal failure for people with HIV, over and above that seen in the HIV-negative population, has been associated with a low CD4 cell count, a high viral load and treatment with some antiretroviral drugs, especially tenofovir and the protease inhibitors atazanavir, indinavir and lopinavir.
Investigators at the Chelsea and Westminster Hospital wanted to establish the age profile of their patients in the era of antiretroviral therapy and examine changes in kidney function according to age. Declines in kidney function were compared to those observed in age-matched HIV-negative controls and a series of analyses were conducted to see if any risk factors increased the risk of renal failure, which was defined as eGFR below 30 ml/min per 1.73m2.
A total of 15,241 people received HIV care at the hospital between 1996 and 2011. The vast majority (89%) were men, 71% were white and 82% had sex with other men as their HIV risk factors.
The patient population aged over the 15 years of the study. Between 1996 and 2000, 11% of patients were aged 50 and above. This increased to 16% between 2001 and 2004 and to 19% between 2005 and 2008. By 2011, almost a quarter (23%) of HIV-positive individuals receiving care at the hospital were aged 50 and over.
Renal function declined with age in both the HIV-positive people and the HIV-negative control group.
However, for all age groups, kidney function was markedly poorer among HIV-positive people than the HIV-negative control population.
Comparison between people with HIV showed that deterioration of kidney function was of a similar magnitude for patients taking first-line antiretroviral therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) and for patients taking therapy that included a protease inhibitor. Especially marked declines in renal function were observed in antiretroviral-naive people aged 65 and over.
A number of factors were associated with an increased risk of renal failure. Two of these supported the early initiation of antiretroviral therapy. The investigators found that the degree of immune suppression was linked with the risk of renal failure. Compared to people with a nadir CD4 cell count above 350 cells/mm3 – the current threshold for starting HIV treatment in British guidelines – individuals with a nadir count between 200 and 300 cells/mm3 had a two-fold increase in their risk of kidney failure. The risk increased further as immune function declined and a nadir CD4 cell count below 100 cells/mm3 was associated with an eleven-fold increase in risk. Shorter duration of time since diagnosis with HIV – a surrogate marker for being antiretroviral naïve – was also associated with an increased risk of kidney failure.
Increasing age at the time of nadir CD4 cell count also increased the risk of renal failure. Compared to people in their 40s, individuals in the 50 to 69 age group had a two-fold increase in their risk, and this was increased by a factor of four for people in their 70s.
The investigators therefore conclude that kidney function declines more rapidly in HIV-positive people compared to matched HIV-negative controls. They believe that HIV itself plays an important role in renal disease, suggesting “that antiretroviral therapy should be started soon after diagnosis to reduce end-organ damage”. The researchers also believe that the ageing of the HIV-infected population will require improved linkage and integration of HIV services with renal care and services for other co-morbidities.
Mandalia S et al. The effect of HIV infection, ART and ageing on renal function in PLHIV, Chelsea and Westminster Hospital, London, UK 1996-2012. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, poster MOPE081, 2013.