All symptomatic patients with HIV disease should begin antiretroviral therapy right away, according to new guidelines published by the International AIDS Society-USA and presented at the International AIDS Conference held in August in Toronto. Based on several new developments, the revision marks the seventh time since 1996 that the organization has updated its recommendations for HIV treatment.
For patients without symptoms, therapy should be initiated at some point after the CD4 cell count falls below 350 per μl but before it drops as low as 200 per μl, according to the new update. Other parameters to consider include patient readiness, rate of CD4 cell count decline, and plasma HIV-1 RNA level. Previous provider reluctance to begin treating patients too early may be pacified now that newer formulations and combinations of drugs have improved tolerance and convenience, the guidelines noted.
Refinements have also been made as to the choice of initial regimen. As before, the preferred medication cocktail remains two nucleoside (or nucleotide) reverse transcriptase inhibitors (nRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) boosted with ritonavir.
A NNRTI-based regimen containing efavirenz (Sustiva, Bristol-Myers Squibb) is both efficacious and easy to use, according to the guidelines; however, the teratogenic risk during the first trimester requires adequate contraception. The convenience of one pill a day is offered with a triple formulation combination of efavirenz, tenofovir, and emtricitabine (Atripla, Gilead). Nevirapine (Viramune, Boehringer Ingelheim) is another NNRTI with similar activity to efavirenz and is safe during pregnancy, but should be avoided in women with CD4 counts higher than 250 per μl and in men with counts higher than 400 per μl.
For initial ritonavir-boosted PI-based regimens, the most data exist for lopinavir (Kaletra, Abbott), which has been approved for once-daily dosing in treatment-naïve patients in the United States. The guidelines point out that incidence of diarrhea is greater when lopinavir is given as 800 mg with 200 mg of ritonavir once daily than when taken as lopinavir 400 mg with 100 mg ritonavir twice daily. Atazanavir (Reyataz, BMS) is reported as having the potential advantage of causing less hyperlipidemia than other ritonavir-boosted PIs, according to the guidelines. Its major side effect is hyperbilirubinemia, which is more common in patients with the uridine 5' di-phosphoglucuronosyl transferase (UGT) polymorphism. Fosamprenavir (Lexiva, GSK) data support its use in initial regimens, while the soft-gel formulation of saquinavir (Fortovase, Roche) and ritonavir is considered inferior to other combinations-perhaps due to differences in tolerability, said the guidelines. The hard-gel formulation, however, had good virologic efficacy.
New drugs mentioned in the revision include both darunavir (Prezista, Tibotec) and tipranavir (Aptivus, Boehringer Ingelheim). "Overall, darunavir is a PI that we plan to use in heavily experienced patients, and ideally in combination with enfuvirtide," Hardy said. She went on to explain that tipranavir is also a PI that is active against multiresistant virus and is used in patients who have been exposed to three or four HIV regimens before and have developed resistance.
"It will be very important to talk about pill burden, dosing frequency, possible side effects (both short- and long-term) to decide which regimen to select," Hardy said of pharmacists. "The choice should ensure that efficacy is optimal as well as long-term adherence."
The 2006 International AIDS Society guidelines, "Treatment for Adult HIV Infection," also provide recommendations that address patient monitoring, changing therapy for toxicity and/or treatment failure, and providing antiretro-viral therapy in special populations. They can be accessed on-line at the Web site of the Journal of the American Medical Association: http://www.jama.com/.