Tenofovir disoproxil fumarate is one of the NRTI agents recommended for use in pregnancy (Table 49–5). The combination of tenofovir and emtricitabine is recommended as pre-exposure prophylaxis to reduce HIV acquisition in high-risk persons.
Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation. Since tenofovir is formulated with lactose, these may occur more frequently in patients with lactose intolerance. Cumulative loss of renal function has been observed, possibly increased with concurrent use of boosted PI regimens. Acute renal failure and Fanconi’s syndrome have also been reported. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Serum creatinine levels should be monitored during therapy and tenofovir discontinued for new proteinuria, glycosuria, or calculated glomerular filtration rate <30 mL/min. Tenofovir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D; loss of bone mineral density and osteomalacia have been reported. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. Concurrent use of probenecid is contraindicated. Tenofovir levels may increase, and levels of telaprevir decrease, when these agents are co-administered. Due to its activity against HBV, exacerbation of HBV may occur if therapy is interrupted or discontinued in patients co-infected with HIV and HBV.
Tenofovir alafenamide is a phosphonoamidate prodrug of tenofovir that is currently available in co-formulation with other antiretroviral agents (with emtricitabine, with elvitegravir plus cobicistat plus emtricitabine, and with rilpivirine plus emtricitabine). Plasma levels of active tenofovir in plasma are approximately 90% lower with tenofovir alafenamide than with tenofovir disoproxil, since metabolism occurs in lymphocytes and macrophages (as well as hepatocytes and some other cells) rather than blood.
Tenofovir alafenamide is a substrate of P-glycoprotein, and levels of tenofovir can be affected by inhibitors or inducers of P-glycoprotein. Ritonavir and cobicistat can increase plasma concentrations of tenofovir, while darunavir can decrease tenofovir concentrations.
Tenofovir alafenamide appears to have less renal and bone toxicity than tenofovir disoproxil fumarate; however this is still under investigation. It does not require dose adjustment in patients with creatinine clearance >30 mL/min.
Tenofovir alafenamide is a substrate of P-glycoprotein, and levels of tenofovir can be affected by inhibitors or inducers of P-glycoprotein. Ritonavir and cobicistat can increase plasma concentrations of tenofovir, while darunavir can decrease tenofovir concentrations.
Adverse effects appear to be uncommon but may include gastrointestinal symptoms or headache. Tenofovir alafenamide is active against hepatitis B and has been approved for treatment of HBV infection.