Viral load associated with kidney function in patients with HIV

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HIV viral load is associated with changes in kidney function, investigators report in the June 1st edition of AIDS. The US researchers found that a higher viral load was associated with a deterioration in kidney function. By contrast, a fall in viral load and an increase in CD4 cell count were accompanied by an improvement in the health of the kidneys. “It follows therefore that treatment of active viral replication with HAART [highly active antiretroviral therapy] may slow the progression of kidney dysfunction”, write the investigators.

Kidney disease has long been recognised as a possible complication of HIV infection. HIV-associated nephropathy (HIVAN) was associated with advanced HIV disease. This condition has become much rarer since effective HIV treatment became available. However, kidney dysfunction remains widespread in patients with HIV. Much of this can be attributed to traditional risk factors including high blood pressure. There is also concern that treatment with some anti-HIV drugs may also adversely affect the kidneys. Some research has also highlighted immune suppression and a higher viral load as risk factors for kidney disease.

Measuring cystatin C has been shown to be an accurate way of assessing glomerular filtration rate (GFR), an important indicator of kidney function.


detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.


The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.


Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 


A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

Investigators from the FRAM study, which was originally intended to monitor body fat changes in HIV-positive individuals, designed a case-controlled study to assess changes in kidney function in 554 HIV-positive individuals and 230 controls. Kidney function was monitored over a five year period.

Surprisingly, the investigators found that during follow-up the HIV-infected patients showed a slight improvement in kidney function compared to the deterioration in kidney function witnessed in the controls (p = 0.012).

However, the investigators also noticed that there was a much broader distribution of kidney function within the HIV-positive patients than the controls. A larger proportion of HIV-positive individuals than HIV-negative controls had declining kidney function (18% vs. 13%, p = 0.002) and improving kidney function (26% vs. 6%, p < 0.0001).

After controlling for possible confounding factors, the investigators found that compared to the controls (p = 0.0004), HIV-positive patients had twice the risk of a decline in their kidney function, but were seven times more likely to experience an improvement (p < 0.0001).

By the end of follow-up, 8% of HIV-positive patients had developed chronic kidney disease compared to 1% of controls (0 = 0.014).

Next the investigators looked at the factors associated with declining and improving kidney function in the HIV-positive patients. They found that an increase in viral load was associated with a decline in kidney function (p = 0.011) whereas a fall in viral load was associated with an improvement in kidney function (p = 0.0003).

A total of 42% of patients with a detectable viral load experienced a decline in their kidney function. It remained unchanged in 31% of with a detectable viral load and improved in 15%. The association between a detectable viral load and declining kidney function was significant (p < 0.0001).

Further analysis showed that a higher baseline HIV viral load was also associated with a worsening of kidney function (p = 0.0002). An increase in CD4 cell count was, by contrast, associated with an improvement (p = 0.05).

Other factors associated with a deterioration in kidney function were older age (p = 0.016), higher baseline glucose (p < 0.0001), use of medication to reduce blood pressure (p = 0.011), and an increase in LDL cholesterol (p = 0.007).

No association was found between the use of any anti-HIV drug and the worsening of kidney function. This was despite the fact that use of tenofovir (Viread) increased significantly during follow-up (tenofovir may worsen kidney function in people with pre-existing impairment). By the end of the study 59% of individuals had taken this drug, the average duration of use being two years.

“We found that HIV-infected participants were more likely than HIV-negative controls to have clinically significant decline in kidney function and to progress to chronic kidney disease…however, we also found that 26% of HIV-infected persons manifested clinically significant improvements in kidney function”, comment the investigators.

They note that increases in viral load accompanied a decline in kidney function and that a fall in viral load was associated with improved kidney function. The investigators therefore write: “Our results suggest that HIV viral replication is a primary pathogenic factor in the development of kidney disease in HIV-infected persons and a potential therapeutic target for HIV-related kidney disease.”


Longenecker CT et al. HIV viremia and changes in kidney function. AIDS 23: 1089-96, 2009.