HIV Treatment Bulletin - Vol. 5, No. 7, August/September 2004

Simon Collins, HIV i-Base

Tenofovir is now widely used in treatment naïve patents and 3-year data presented at the conference showed in several analysis from the 903 Study and numerous smaller studies continued to support its improved lipid profile and reduced peripheral lipoatrophy and neuropathy, when used with 3TC and efavirenz, and compared to d4T. [1]

Several posters also showed more surprisingly that the incidence of kidney-related side effects including increased creatinine, proteinuria and renal failure may not be higher in patients using tenofovir in their combination, or compared to patients not on treatment. In the 903 Study <1% in each arm (2/296 in each arm) developed serum creatinine >2.0 mg/dL and mean change from baseline in creatinine clearance (ml/min) was greater in the d4T than TDF arm (+7 vs +1). [2]

Stebbing and colleagues, in a case control anaylsis classified patients with creatinine ever >120 umol/l in a large clinic database by antiretroviral exposure and found a lower rate in patients on treatment including tenofovir, compared to those who were antiretroviral naïve (rate ratio versus no anti-ARV 0.22, 95% CI 0.07 to 0.69, p < 0.001). [3] Of the 1,058 individuals who were exposed tenofovir DF, 84 patients (8%) experienced a creatinine > 120 µmol/l subsequent to exposure. An alternative aetiology of renal dysfunction was found in 75 (90%) of these individuals.

Preexisting kidney dysfunction, or concomitant use of other nephrotoxic medications does appear to increase the risk of nephrotoxicity though. [4] For example, in a retrospective chart review from May 2002 to September 2003 of 507 patients attending Jackson Memorial Hospital, Miami, Chin-Beckford and colleagues indentified six patients whose creatinine increased with tenofovir and normalised upon discontinuation. Mean age was 53 years and 5/6 subjects had either hypertension or diabetes or both. Most subjects did not have a renal dose adjustment for tenofovir.

Another study showed that cystatin levels may be more sensitive marker for tenofovir-associated kidney dysfunction. Mauss and colleagues measured serum and urine levels of creatinine, cystatin C and electrolytes over 24 hours in 74 patients using tenofovir and 84 patients who had never used tenofovir. Diabetes mellitus, hypertension, liver cirrhosis or known renal disease were exclusion criteria for the study. [5]

Results showed statistically significant differences in cystatin clearance (normal >80 ml/min) between the two groups, but no differences in electrolytes and creatinine were observed. No patient had a nephrotic or fanconi-like syndrome and proteinuria in three patients resolved on discontinuation of tenofovir.

Cystatin may therefore be a more sensitive marker than creatinine, that could be used in the future to help identify patients at risk from renal toxicity prior to using tenofovir, and in monitoring patients using this drug.

Appropriate tenofovir dosage adjustments for patients with renal dysfunction are included in the product characteristics and should be used appropriately. Renal function is especially important in patients with advancing age and co-morbidity factors including diabetes and hypertension.

References

All references are to the programme and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand.

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