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
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
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
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.”