7.2.1 First-line ART for adults

Consolidated ARV guidelines, June 2013

Rationale and supporting evidence: TDF toxicity

A systematic review on TDF toxicity (Web Annex) indicates that TDF has a low rate of renal toxicity in the short to medium term, especially among people with pre-existing, or risk factors for, renal disease. Prospective cohort data show that TDF is associated with modest reduction in renal function (measured by the decrease in the estimated glomerular filtration rate) (130,131) and reduction in bone mineral density, but the clinical significance and magnitude of these side effects, especially with prolonged therapy, need to be investigated further.

Further research is also needed to determine whether laboratory screening and monitoring of TDF toxicity should be routine or undertaken only in high-risk populations, such as people with hypertension or diabetes or those using boosted PIs. Since TDF renal toxicity is usually tubular, glomerular function tests do not provide a direct measure, and no other simple test can detect renal tubular toxicity. Section 7.4 discusses this issue further.

Evidence suggests that the overall improvement in renal function resulting from ART can offset the risk of TDF toxicity among people with HIV who do not have secondary renal disease.