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Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors

NRTIs block an enzyme of the HIV called reverse transcriptase that allows HIV to infect human cells, particularly CD4 lymphocytes. Reverse transcriptase converts HIV genetic material, which is RNA, into human genetic material, which is DNA. The human-like DNA of HIV then becomes part of the infected persons' own cells, allowing the cell to produce copies of the HIV that can then go on to attack other not yet infected cells. Thus, blocking reverse transcriptase prevents HIV from taking over (infecting) human cells.

In general, most antiviral regimens for HIV disease contain a backbone of at least two NRTIs. The NRTIs include ZDV, d4T, ddI, zalcitabine (HIVIDTM, ddC), 3TC, FTC, ABC or TDF. FTC and 3TC are highly related compounds and, although data is somewhat limited, most experts agree that they probably can be used interchangeably. That said, many combinations of NRTIs can be used together, with current guidelines generally recommending either ZDV or TDF be used with 3TC or FTC. Alternative regimens that include ABC with 3TC (or FTC) and ddI with 3TC (or FTC) have been shown to be quite effective in some studies. Because of drug interactions and toxicities it is generally recommended that 3TC not be used with FTC or d4T with either ZDV or ddI. In addition, recent data has suggested that there may be reduced efficacy and possibly increased toxicity when TDF and ddI are used together. In fact, in the most recent DHHS guidelines it is explicitly stated that this NRTI combination should not be used with EFV in light of the surprisingly poor virologic response.