Nucleoside Reverse Transcriptase Inhibitors (NRTIS)

substantial progress continues to be made in the arena of antiretroviral drug development. prn is again proud to present its annual review of the experimental agents to watch for in the coming months and years. This year’s review is based on a lecture by Dr. Roy M. Gulick, a longtime friend of prn, and no stranger to the antiretroviral development pipeline. To date, twenty-two antiretrovirals have been approved by the Food and Drug Administration (fda) for the treatment of hiv infection. In addition to the development of new drugs and drug classes with unique potency advantages, a number of older antiretrovirals have been reformulated to allow for more simplified dosing. Examples include fosamprenavir (Lexiva) tablets, replacing the amprenavir (Agenerase) liquid capsules; liponavir/ritonavir (Kaletra) tablets, replacing the liquid capsules; and the new tablet formulation of saquinavir (Invirase), replacing the 200-mg capsules of Invirase and the need for Fortovase. Additionally, the development of fixed-dose combination tablets has considerably improved treatment acceptance. For the first time, a widely used complete drug regimen is available to take as one pill once per day. Atripla, a fixed-dose combination drug containing daily doses of tenofovir (Viread), emtricitabine (Emtriva), and efavirenz (Sustiva), was approved by the fda on July 12, 2006. Even with increasingly simplified treatment regimens, challenges still remain in finding products with minimal toxicity and optimized resistance profiles. To achieve optimal viral suppression, there is also a need for agents that penetrate viral reservoirs and target new portions of the hiv lifecycle. Fortunately, the antiretroviral drug pipeline contains several promising agents that may address these needs. A summary of these agents is shown in Table 1. Some of these are new members of existing drug classes, including reverse transcriptase inhibitors and protease inhibitors, and some are members of new drug classes, such as integrase inhibitors.