Tenofovir (Viread) has an important interaction with the nucleoside reverse transcriptase inhibitor ddI (didanosine, Videx / VidexEC), in three ways:

• Combining the drugs results in increased exposure to ddI^[1]. This can lead to a greater risk of ddI-related side-effects such as lactic acidosis, pancreatitis and peripheral neuropathy, which have been fatal in some cases^[2][3][4][5]. Research suggests that reducing the once-daily dose of ddI from 400 to 250mg should result in acceptable exposure to ddI when taken with the standard dose of tenofovir daily, although there have been reports of lactic acidosis even with this reduced dose of ddI^[6][7].
• The combination of ddI and tenofovir has also been linked to falls in CD4 cell counts in treatment-experienced patients who switch to the drugs as well as patients who are taking tenofovir as part of their first treatment regimen^[8][9]. However, this may be prevented by using a lower dose of 250mg ddI in patients taking tenofovir^[10].
• The combination of ddI and tenofovir with nevirapine (Viramune) or efavirenz (Sustiva) may also be problematic due to a higher risk of virologic failure^[11][12][13].

Gilead and ddI’s manufacturer Bristol-Myers Squibb issued a ‘Dear Doctor’ letters in November 2004 and March 2005 warning healthcare providers not to prescribe tenofovir and ddI together unless absolutely necessary, because of the risks of side-effects and treatment failure.

When a patient is taking tenofovir as well as other medicines that are known to cause kidney toxicity, there may be an increased risk of kidney side-effects. If co-administration with drugs such as ganciclovir (Cymevene), foscarnet (Foscavir), pentamidine (Pentacarinat), amphotericin (Fungilin / Fungizone), vancomycin (Vancocin), interleukin-2, cidofovir (Vistide) or the aminoglycosides cannot be avoided, weekly monitoring of kidney function is recommended. ddI can also increase the risk of kidney toxicity, possibly through damaging the mitochondria in the kidney^[14].

Tenofovir levels are also slightly increased when dosed with ritonavir-boosted lopinavir (Kaletra) or atazanavir (Reyataz). Although some studies have reported no negative effects of tenofovir on lopinavir concentrations in treatment-experienced patients, significant reductions in lopinavir and ritonavir minimum concentrations have been seen^[15][16]. Tenofovir also decreases atazanavir levels^[17]. When the two drugs are taken together, it is recommended that atazanavir be boosted with ritonavir (Norvir).