Creatinine elevations during abacavir or tenofovir treatment are more likely in patients with lower CD4 cell counts, according to a review of British Columbia patients presented yesterday at the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.
Creatinine elevation is an indicator of kidney damage, a rare potential side effect of tenofovir treatment.
476 patients who began tenofovir treatment during 2002 were compared with 430 abacavir-treated patients in the British Columbia state database, which tracks all patients receiving antiretroviral therapy in the Canadian province. Laboratory measurements were available for 322 tenofovir-treated patients and 430 abacavir treated patients. Creatinine elevation was defined as 1.5x upper limit of normal (ULN), a different definition from that used in US Food and Drug Administration-mandated analysis of tenofovir clinical trials.
Tenofovir-treated patients had significantly greater duration of antiretroviral exposure (P<0.001), lower viral load and higher cd4 cell count (230 vs 190 cells/mm3, p<0.001), and were older (p<0.001). creatinine levels were similar (80 vs 82umol/l) and similar proportions had mild elevations >133 umol/l (3.1 vs 3.7%). Approximately one-third of each group had a prior AIDS diagnosis.
Six tenofovir treated patients (1.3%) discontinued the drug due to creatinine elevations during the follow-up period, compared to no abacavir-treated patients. Elevations were observed in 7.1% of tenofovir-treated patients compared to 3.1% of abacavir treated patients after six months of therapy (p=0.003).
Multivariate analysis showed a relative risk of 2.54 for creatinine elevation associated with tenofovir treatment when compared with abacavir treatment, and a relative risk of 1.4 for creatinine elevation with every 100 cell decrement in CD4 cell count.
The authors concluded that in those with normal renal function at baseline, those with lower CD4 cell counts are at greater risk of creatinine elevation when compared to abacavir-treated patients.
This study could not capture the known risk factor of previous history of nephrotoxic drug use, and did not analyse concomitant antiretroviral use that might have elevated tenofovir levels.
It was also unable to capture the prevalence of HIV nephropathy (direct kidney damage caused by HIV), that might potentially predispose to the development of creatinine elevations on tenofovir.
Of note, the background rate seen in abacavir-treated patients was 3.1% after six months of treatment. Using a different measurement, Gilead Sciences data on file shows that 0.3% of French patients receiving tenofovir in the expanded access programme prior to licensing developed grade III or IV creatinine elevations.
Harris M et al. Increases in creatinine during therapy with tenofovir DF. Antiviral Therapy 8 (Suppl 1): S197 (abstract 55), 2003.