Tenofovir Disoproxil Fumarate May Cause Kidney Damage in HIV

Renal damage appeared to decrease in most patients with HIV who were required to discontinue tenofovir disoproxil fumarate (TDF) (Viread/Gilead) due to nephrotoxicity, according to a recently published observational study.

The authors also highlighted that improvement occurred more rapidly in younger patients. While nephrotoxicity associated with TDF has been well documented, prospective studies have been lacking.

"This is one of the few prospective studies that focus specifically on assessing progression of renal abnormalities, including urinary markers, after withdrawing of TDF," lead author Anna Bonjoch, MD, PhD, Internal Medicine Service, Autonomous University of Barcelona, Barcelona, Spain said in a news release.

The researchers followed 59 patients who had received a treatment regimen containing TDF for at least three months and had to discontinue the medication because of nephrotoxicity. The patients were followed for 18 months after the treatment was discontinued, corresponding to the median time for normalization of renal values found in a retrospective study.

According to Bonjoch and colleagues, the most frequently reported renal abnormality to prompt discontinuing TDF was a mildly altered proteinuria/creatine ratio. Five patients presented with occasional proteinuria, and two with sustained proteinuria.

All but 2 patients demonstrated normal renal function sometime during the follow-up period, with creatinine and estimated glomerular filtration rates (eGFR) measured within normal limits between four and 24 weeks (median 12 weeks).

One of the two patients regained normal proteinuria/creatinine ratio, but had an abnormal eGFR at baseline, which improved without reaching normal values. However, the other patient showed only a slight improvement in proteinuria/creatinine ratio. Not all patients with normalized values maintained them throughout the follow-up period. Thirty-five patients (59.3%) did sustain normality in all the parameters, while 13 (22%) improved without complete normalization and 11 (18.7%) remained without improvement.

The team noted that younger age (median 49.5 years) was associated with full recovery occurring within six months after TDF discontinuation, compared to older patients (55 median years) who generally required longer than six months for normalization. Other factors, such as discontinuing TDF without changing other drugs in regimen or switching from TDF to abacavir (Ziagen/ GlaxoSmithKline), time on TDF or an antiretroviral treatment, a concurrent protease inhibitor, or having comorbidities were not found to have statistically significantly contributed to findings.

The researchers were unable to find a common element among those patients who did not maintain a complete recovery through the follow-up, attributing this to the "multifactorial nature of these alterations, or to some intercurrent process."

Their prospective study after discontinuing tenofovir disoproxil fumarate treatment for HIV, “Prospective Study to Assess Progression of Renal Markers after Interruption of Tenofovir due to Nephrotoxicity,” was published online in December in BioMed Research International.