NRTI backbone in HIV treatment: will it remain relevant?

Nucleoside reverse transcriptase inhibitors (NRTIs) remain a critical component of therapy for HIV-infected patients. The drugs are effective, relatively inexpensive and an important component of antiretroviral therapy (ART), particularly in areas where the introduction of effective therapy has been delayed. They are an essential part of initial therapy for HIV and for prevention of mother-to-child transmission; however, toxicities and resistance may limit their use. The role for pre-exposure prophylaxis (PrEP) to reduce sexual transmission of HIV is still undefined, but this use may have a significant impact on NRTI resistance worldwide, most particularly in areas where subtype C predominates. With increasing prevalence of resistant HIV, the approval of new agents that are effective against resistant virus, and those that use novel cellular targets, are essential. Large studies are now in progress examining the safety and efficacy of NRTI-sparing regimens, but results are not currently available. NRTIs may lose relevance in the not distant future unless steps are put in place to reduce the development and spread of NRTI-resistant viruses, and new NRTIs with minimal toxicity are developed that have a novel resistance profile. This article describes the principal NRTIs, their mechanism of action, and resistance and selected toxicities of the class and of the individual drugs.