Human Immunodeficiency Virus (HIV, AIDS) (cont.)

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What are nucleoside and nucleotide analogue reverse transcriptase inhibitors?

NRTIs block an enzyme of the human immunodeficiency virus called reverse transcriptase that allows HIV to infect human cells, particularly CD4 cells or 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 person's own cells, allowing the cell to produce RNA 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 (HIVID, ddC), 3TC, FTC, abacavir (Ziagen, ABC), or TDF. The NRTIs 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 the fixed-dose combination of TDF with FTC (Truvada) or, in select regimens or as an alternative, the fixed-dose combination of ABC/3TC (Epzicom). Much less frequently used regimens would be the fixed-dose combination of ZDV and 3TC (Combivir) or ddI plus 3TC or FTC. ABC has been associated with severe allergic reactions in approximately 5% of patients. Recent studies have shown that a blood test (HLA-B*5701) can be performed to determine who is at risk for this reaction so that the drug can be avoided in these individuals and be used in others with greater confidence that there will not be such a reaction. In fact, when available, it is now the standard of care to perform this test prior to initiation of ABC.

What are the usual dosing schedule and meal restrictions for NRTIs?

  ZDV d4T ddI ddC 3TC ABC TDF FTC
Dose in each pill (mg) 300 30 or 40 100 or 400 0.75 150 or 300 300 300 200
Schedule 1 twice a day 1 twice a day
2 (100) twice a day or
1 (400) once a day
1 thrice a day 1 (150) twice a day or 1(300) once a day 1 twice a day or 2 once a day 1 once a day 1 once a day
Meal restrictions None None
30 minutes before or 60 minutes after a meal
None None None None None
ZDV, zidovudine; d4T, stavudine; ddI, didanosine; ddC, zalcitabine; 3TC, lamivudine; ABC, abacavir; TDF, tenofovir; FTC, emtricitabine.

The following are available fixed-dose combination pills of NRTIs:

  • ZDV/3TC (300 mg/150 mg) as Combivir; one twice per day
  • ZDV/3TC/ABC (300 mg/150 mg/300 mg) as Trizivir; one twice per day
  • ABC/3TC (600 mg/300 mg) as Epzicom; one per day
  • TDF/FTC (300 mg/200 mg) as Truvada; one per day

These are standard doses for average-sized adults, and dosing may vary depending upon the weight of a patient. Certain combinations of drugs in this class should generally be avoided, including d4T with ZDV or ddI, 3TC with FTC, and TDF with ddI.

Medically Reviewed by a Doctor on 8/5/2014

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