Anti-HIV Drugs, eGFR Decline Linked

ATLANTA—Nephrologists should be vigilant for signs of a rapid decrease in estimated glomerular function rate (eGFR) in their HIV-positive patients who are taking certain antiretroviral drugs, according to new study results.

In a paper published online ahead of print in the Journal of Infectious Diseases (JID) a multinational team documented that cumulative use of tenofovir and ritonavir-boosted atazanavir independently predicted progression to confirmed (more than three months apart) eGFR below 70 mL/min/1.73m2 (a threshold below which the authors speculated intervention may begin to occur) from initial normal eGFR levels (greater than 90) during a median follow-up of 4.5 years.

Sustained use of ritonavir-boosted lopinavir is a predictor of both confirmed eGFR above 70 and moderate chronic kidney disease (CKD; confirmed eGFR below 60). Further, the investigators showed that individuals with a current eGFR of 60-70 discontinued tenofovir at a rate 1.72 times greater than those with current eGFRs of 90 or higher. Cumulative tenofovir use and ritonavir-boosted atazanavir use were associated with an 18%-19% greater likelihood per additional year of use of a reduction in eGFR to confirmed 70 or below, while sustained use of ritonavir-boosted lopinavir was associated with an 11% greater likelihood of reaching this confirmed level of eGFR and a 22% increased likelihood of developing moderate CKD per additional year of use.

The data are from the D:A:D study, a long-term prospective cohort study of 49,734 HIV-positive patients in the U.S., Europe, and Australia.

However, in a poster presented at the 20th Conference on Retroviruses and Opportunistic Infections, the same members of the D:A:D team reported that neither recent nor current use of potential nephrotoxic antiretroviral drugs (ARVs) was associated with advanced CKD (confirmed eGFR below 30) or end-stage renal disease (ESRD; dialysis for more than three months or renal transplantation). They documented a high rate of discontinuation of some ARVs, particularly tenofovir, when patients' eGFRs fell below 60, however.

“Given the increasing awareness of the nephrotoxic potentials of especially tenofovir clinicians are prone to react to a declining eGFR in patients on this drugby either dose adjusting or switching to a more kidney-friendly treatment option if possible,” commented lead author Lene Ryom, MD and D:A:D study coordinator, from the Copenhagen HIV Programme. “We therefore believe the reason why we don't observe a positive association between tenofovir use and advanced CKD/ESRD in our cohort is likely that patients on tenofovir switched away from the drug long before reaching severe levels of chronic kidney diseases”

The results presented in the conference poster extended the findings of the JID paper, showing that after adjusting for confounding factors, patients who had previously used tenofovir but had discontinued the drug had similar rates of advanced CKD or ESRD as patients who had never been exposed to tenofovir. The poster revealed no increased likelihood of developing advanced CKD or ESRD with current or past use of ritonavir-boosted lopinavir, atazanavir, ritonavir-boosted atazanavir, or other boosted protease-inhibitor-based ARV treatment.

“Our findings do not, however, exclude the possibility that such ARV relations [with advanced CKD or ESRD ] may exist in populations without access to regular eGFR screening,” the investigators noted in their poster. “It also cannot be excluded that such issues may arise with more prolonged use of these ARVs in an older HIV-positive population at higher underlying risk of renal impairment.”

The researchers also confirmed other factors traditionally associated with developing advanced CKD or ESRD, including diabetes, hypertension, lower baseline eGFR, current smoking and lower current CD4 cell counts.

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