The greatest challenge for predicting HIV medication failures, second to drug efflux mechanisms or interactions, is the relative lack of specificity of transport systems for HIV drugs. There is an increasing pool of data to suggest that nucleoside analogs are not only transported by nucleoside transporters, but also by OCTs. MRP4, for example, has been linked to the efflux of nucleoside monophospate analogs, and, in one study, overexpression of MRP4 messenger ribonucleic acid led to impaired antiviral efficacy of a variety of nucleoside analogs, including azidothymidine. birth control pills
OCTs have also been shown to transport AZT, and there may be cross-reactivity between OCTs and nucleoside transporters. This is also relevant to nucleoside chemotherapeutic agents, such as cytosine arabinoside. Furthermore, protease inhibitors including indinavir, nelfi-navir, ritonavir and saquinavir have all been shown to inhibit (but are not substrates for) transport via the human OCT1. This suggests that HIV protease inhibitors may potentially inhibit the uptake and elimination of cationic drugs.