Supplemental Reading

Bartlett JA. Addressing the challenges of adherence. J Acquir Immune Defic Syndr 2002;29 Suppl 1:S2-S10.

Campiani G et al. Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: Past, present, and future perspectives. Curr Pharm Des 2002;8:615-657.

Greene WC and Peterlin BM. Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy. Nat Med 2002;8:673-680.

Jiang S, Zhao Q, and Debnath AK. Peptide and non-peptide HIV fusion inhibitors. Curr Pharm Des 2002;8:563-580.

Moyle G. Use of HIV protease inhibitors as pharma-coenhancers. AIDS Read 2001;11:87-98.

Pierson T et al. Characterization of chemokine receptor utilization of viruses in the latent reservoir for human immunodeficiency virus type 1. J Virol 2000;74:7824-7833.

Piot P et al. The global impact of HIV/AIDS. Nature 2001;410:968-973.

Sepkowitz KA. AIDS: the first 20 years. N Engl J Med 2001;344:1764-1772.

Setti M et al. Identification of key mutations in HIV reverse transcriptase gene can influence the clinical outcome of HAART. J Med Virol 2001;64:199-206.

Sonza S and Crowe SM. Reservoirs for HIV infection and their persistence in the face of undetectable viral load. AIDS Patient Care STDS. 2001;15:511-518.

Tarrago-Litvak L et al. Inhibitors of HIV-1 reverse transcriptase and integrase: Classical and emerging therapeutical approaches. Curr Pharm Des 2002; 8:595-614.

Tozser J. HIV inhibitors: Problems and reality. Ann N Y Acad Sci 2001;946:145-159.

^ Case Study HIV and Nutriceuticals

Jerome R. is HIV positive and has been taking saquinavir 1200 mg tid and zidovudine 200 mg tid for the past 8 months. During this time, his CD4 count raised from 200 cells/mm3 to 725 cells/mm3. Two months later, Mr. R returned to his physician with a severe herpes outbreak on one side of his face. His CD4 count had fallen to 280 cells/mm3. What happened?

Answer: Two months ago, Mr. R. began taking St. John's wort to counteract depression. St. John's wort is a potent inducer of intestinal and hepatic CYP3A4. Saquinavir undergoes extensive first-pass metabolism by intestinal CYP3A4 and is metabolized in the liver by CYP3A4. The use of St. John's wort is contraindicated for individuals taking pro-

tease inhibitors because it may decrease protease inhibitor concentrations to subtherapeutic levels, resulting in the loss of virological response and possible resistance to the protease inhibitor. In this case, it appears that saquinavir was no longer present at an effective concentration and the HIV virus became resistant to zidovudine. Discontinuation of St. John's wort and a change in treatment regimen, perhaps to two different NRTIs and an NNRTI, are in order. Mr. R's depression should be treated with a different agent. Many antidepressants are metabolized by cytochrome P450 systems; thus, a reduction in antidepressant dosage may be necessary because NNRTIs and protease inhibitors inhibit cytochrome P450 isoenzymes.

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