Kidney injury and anti-HIV drugs – the latest from the DAD study
The DAD study is a very large observational study that has recruited nearly 50,000 HIV-positive participants from Australia, Europe and the U.S. From time to time, DAD researchers undertake analyses of their findings and publish them.
In its latest report, the DAD team analysed data from about 22,000 HIV-positive participants, some of whom saw their kidney health decline over time. DAD researchers found that, over time, participants who used the following drugs had an increased risk for kidney dysfunction:
- tenofovir (Viread)
- atazanavir (Reyataz) + ritonavir (Norvir)
- lopinavir-ritonavir (Kaletra)
The study’s findings are discussed below.
Researchers scoured the DAD database (currently containing information on about 50,000 HIV-positive people) for participants who initially had normal kidney function when they entered DAD. Normal kidney function was defined as having an estimated glomerular filtration rate (eGFR) of 90 ml/minute or greater. Also, participants had to have at least three subsequent eGFRs in the database so that researchers could see how this assessment changed over time. Using this screening, the research team found 22,603 eligible HIV-positive participants on whom they focused their analyses.
The average profile of participants upon entering the study was as follows:
- gender – 73% men, 27% women
- age – 39 years
- CD4+ count – 440 cells
- HIV viral load – 126 copies/ml
- duration of HIV infection – 5 years
- co-infected with hepatitis B virus – 12%
- co-infected with hepatitis C virus – 12%
- used tobacco – 44%
- higher-than-normal blood pressure – 8%
- diabetes – 3%
Participants were monitored for about five years.
Results—Declining kidney health
About 468 participants (2%) had worsening kidney health over the course of the study. These participants entered the study with an eGFR greater than 90 ml/min but by the end of the study had an eGFR of 70 ml/min or less.
The DAD researchers also found that among participants whose kidney health was declining (as assessed by decreased eGFR results) and whose doctors stopped prescribing the offending treatment, the eGFRs were less likely to continue to fall. Unfortunately, the study was not designed to explore the reversibility of kidney dysfunction; that will need to be done in another study. Still, this finding is a positive sign that perhaps kidney damage caused by some HIV treatments is not permanent.
Reduced kidney function
Taking many factors into account, the length of time that participants spent on treatment with the following drugs was associated with decreased kidney health:
- atazanavir + ritonavir
These associations were statistically significant.
Other factors associated with a declining eGFR were as follows:
- increasing age
- being female
- injecting street drugs
- a history of AIDS
Bear in mind
Among healthy HIV-negative people, researchers expect to see a decline in eGFR of about 1.0 ml/min per year. However, in the present study, a substantial decrease (about 20 ml/min) was seen in about 2% of participants.
The good news is that the vast majority (98%) of participants did not have a significant decline in the health of their kidneys.
Our next report puts the latest results from DAD into context.
—Sean R. Hosein
- Ryom L, Mocroft A, Kirk O, et al. Exposure to antiretrovirals (ARVs) and risk of renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. Journal of Infectious Diseases. 2014; in press.
- Fine DM, Gallant JE. Nephrotoxicity of antiretroviral agents: Is the list getting longer? Journal of Infectious Diseases. 2014; in press.