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Kidney problems linked to tenofovir use, improve with switch to abacavir
Liz Highleyman, 2013-07-10 13:20:00
with HIV taking tenofovir had a higher rate of kidney impairment than westerners,
according to a study presented at the 7th International AIDS Society Conference
on HIV Pathogenesis, Treatment and Prevention last week in Kuala Lumpur. A related study found that switching from tenofovir to abacavir reduced
Tenofovir (Viread, also in the fixed-dose combinations Atripla, Eviplera and Truvada)
is a component of 'preferred' first-line antiretroviral therapy (ART) in US
treatment guidelines and is increasingly used in resource-limited and middle-income countries due to its good efficacy and tolerability compared with older
agents such as AZT or d4T. Tenofovir can, however, cause kidney toxicity in
Ameet Dravid and colleagues assessed changes in kidney function, determined by
declines in estimated glomerular filtration rate (GFR), among people taking
tenofovir. They also looked at acute kidney injury and recovery of kidney
Most tenofovir kidney studies to date have been done in the US and
Europe. Clinical trials have typically excluded people with pre-existing kidney
problems and do not reflect a 'real world' population, the researchers noted as
The retrospective cohort analysis included 743 people seen at Ruby
Hall Clinic, a tertiary HIV/AIDS clinic in Pune in western
India, who started first-line therapy or switched to a regimen containing
tenofovir between March 2009 and March 2013, and for whom serum creatinine
and creatinine clearance data were available. They were compared with 340 clinic patients who
used tenofovir-free regimens.
About two-thirds of tenofovir recipients were
men and the average age was 43 years. The median baseline CD4 count was low at
168 cells/mm3. Most participants (79%) took tenofovir with non-nucleoside
reverse transcriptase inhibitors (NNRTIs) while 21% did so with protease
inhibitors, usually atazanavir (Reyataz).
Mean GFR at baseline among tenofovir recipients was 96 ml/min using the
MDRD equation or about 90 ml/min using the Cockcroft-Gault calculation method. About 23% had
GFR (by MDRD) of 60 to 90 ml/min, while just 2% had low values in the 30 to 60 ml/min
range. Individuals who started tenofovir with creatinine
clearance <50 ml/min were excluded, as this is a considered a
contraindication. Those who fell below 60 ml/min during the first six months
had their tenofovir discontinued.
The average duration of follow-up was just under
two years. Overall, estimated GFR declined by 6.9 ml/min (by MDRD) after 12
months of follow-up. The decline was 5.5 ml/min for those taking tenofovir with
NNRTIs compared with 11.8 ml/min for those who took tenofovir with protease
Declines continued but were smaller during subsequent years of
tenofovir use. Looking at the entire follow-up period (which extended through
48 months for some patients), annualised declines in GFR (by MDRD) were 5.3
ml/min per year among all participants exposed to tenofovir, 4.2 ml/min per
year for those taking tenofovir plus NNRTIs and 9.2 ml/min per year for those
on tenofovir plus protease inhibitors.
In comparison, GFR fell by just 1.3 ml/min per year among individuals
on tenofovir-sparing regimens – similar
to the normal age-related GFR decline
averaging about 1.0 ml/min/year in the HIV-negative general population.
Baseline CD4 count below 100 cells/mm3 and diabetes were
significant predictors of greater GFR decline, with age over 50 falling just
short of statistical significance.
Thirty-six tenofovir recipients (5%) developed acute kidney injury,
defined as serum creatinine >2mg/dl, creatinine clearance falling to <50
ml/min or a GFR decrease of more than 50% from baseline. Most people (44%) did
so within the first six months on tenofovir, but 19% did so after 24 months.
Three of these patients (8%) required kidney dialysis and four (11%) died.
Significant risk factors for acute kidney injury included low baseline
creatine clearance, CD4 count below 100 cells/mm3, using tenofovir
with protease inhibitors as opposed to NNRTIs, use of other kidney-toxic drugs
and co-existing obstructive kidney disease (for example, kidney stones or
benign prostate enlargement).
Among the 36 individuals
with acute kidney injury, 18 were followed for six months after stopping
tenofovir. During this period, half showed recovery of kidney function, but half
developed chronic kidney disease with estimated GFR remaining at <60 ml/min;
none, however, required long-term dialysis.
"Renal function decline in patients on
tenofovir-based ART was much higher than [in] patients taking tenofovir-sparing
ART," the researchers concluded.
They added that the 5% rate of acute kidney injury
among tenofovir recipients seen in this Indian population was notably higher
than the 1% rate seen in most studies done in high-income western countries.
This difference could be attributable to lower baseline creatinine clearance,
lower CD4 count and higher incidence of co-morbid conditions in this cohort,
Furthermore, they continued, "management of
tenofovir nephrotoxicity in resource-limited settings like India is tough due
to limited access to routine laboratory monitoring, renal replacement therapy
[dialysis] and alternate antiretroviral drugs like abacavir."