TreatmentUpdate 74 - Volume 8, No 10; December 1996
Sean Hosein

The use of the protease inhibitors indinavir and ritonavir in combination with other anti-HIV drugs has caused a dramatic decline in the amount of HIV in the blood of treated subjects. As well, there are reports of recovery from chronic infections. There are many questions about these products for which there are no answers, such as:

* How long will the benefit last?

* Which protease inhibitor is best?

* Which combination of drugs should be used first?

It may be years before answers are available. In the meantime, results from some studies could be used to help guide PHAs and their doctors when making decisions about anti-HIV therapy.

Ritonavir

Researchers in Europe enrolled 7 HIV-infected subjects who had an average CD4+ count of 130 cells for this study. Before entering the trial 6 subjects had used AZT with or without ddC or ddI. Six subjects received ritonavir 600 mg every 12 hours for about 1 year. While enrolled in this study subjects were not supposed to be taking any other anti-HIV agents. The remaining subjects received a reduced dose of ritonavir (300 mg/8 hours) because of its toxicity to his liver.

Results

A year later all subjects had HIV that was resistant to ritonavir. In lab experiments technicians needed 170 times more ritonavir to suppress production of HIV than they did at the start of the study.

What to do?

The researchers state, "long-term ritonavir treatment [leads to the development of HIV that is also resistant to] indinavir and saquinavir." Depending on a PHA's viral load, CD4+ cell count and state of health, doctors may choose to prescribe ritonavir before indinavir or saquinavir. If they do, the other two drugs may not be useful options for their patients in the future.

Saquinavir

Scientists working for Hoffmann-La Roche (the manufacturer of saquinavir) have been conducting research on HIV taken from subjects who received saquinavir 1800 mg/day with or without other anti-HIV drugs. "After 8-12 months...[about] 45% of [subjects had HIV that was resistant to saquinavir]." Among subjects who took saquinavir with AZT and ddC, 22% had HIV that was resistant to saquinavir. The researchers finish their report by noting that PHAs who first used saquinavir can later use other protease inhibitors.

REFERENCES:

1. Schmit J-C, Ruiz L, Clotet B, et al. Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). AIDS 1996;10:995-999.

2. Jacobsen H, H'nggi M, Ott M, et al. In vivo resistance to a Human Immunodeficiency Virus type 1 protease inhibitor: mutations, kinetics, and frequencies. Journal of Infectious Diseases 1996;173:1379-1387.

3. Zingman BS. Resolution of refractory AIDS-related mucosal candidiasis after initiation of didanosine plus saquinavir. New England Journal of Medicine 1996;334(25):1674-1675.

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Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca