Initial therapy for HIV

Initial therapy for HIV

Guidelines for using antiviral therapy have been developed and are updated on a regular basis by an expert panel assembled by the DHHS, the IAS-USA panel, and others. The DHHS guidelines are available at http://www.hivatis.org. The most recent IAS-USA guidelines were published in the Journal of the American Medical Association (JAMA) in the summer of 2008.

Antiviral treatment options have primarily included combinations of two nucleoside analogue reverse transcriptase inhibitors (NRTI), often referred to as "nucs," and one PI, typically with a low dose of RTV, a PI used at low doses to increase the level of the principle PI being used, so called "boosting." Alternative, preferred options include the use of two NRTIs with a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI), the latter often called "non-nucs." These NNRTI-containing combinations generally are easier to take than PI-containing combinations and tend to have different side effects. Recently, NRTIs were combined with the integrase inhibitor raltegravir (Isentress, RAL) with very good viral suppression and tolerability. This novel combination has now been approved by the Food and Drug Administration as another treatment option for those initiating therapy for the first time.

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 T 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 with alternatives being the fixed-dose combinations of ABC/3TC or ZDV/3TC. Other options would include ddI plus 3TC or FTC. ABC has been associated with severe allergic reaction in approximately 5% of patients. Recent studies have shown that a blood test 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.