TreatmentUpdate 76. 9(2): 7-8; March, 1997
Sean Hosein

The protease inhibitor nelfinavir (ViraceptTM) has recently been studied in several clinical trials lasting for 6 months. In study 511, 297 subjects received either AZT/3TC with fake nelfinavir (placebo) or with either nelfinavir 500 mg or 750 mg three times daily. In study 506, 308 subjects received d4T with either nelfinavir (same doses as above) or placebo. Neither subjects nor doctors knew who received nelfinavir. Eleven percent of subjects were female and 89% male. The average CD4+ count at the start of the study was 283 cells and the viral load was 152,511 copies. No subject was supposed to have used protease inhibitors before entering this study.

Results ? viral load

Those subjects receiving nelfinavir 750 mg three times daily had their average viral load fall to about 482 copies. This low level of viral load continued for 6 months. Subjects receiving the lower dose of nelfinavir had a viral load level just slightly higher. The viral load of subjects receiving AZT/3TC fell to about 1,525 copies by the 4th week, after which it increased to nearly 6,000 copies by the 6th month. Subjects who entered the study with a viral load greater than 100,000 copies seemed to get greater suppression of viral activity when using the 750 mg dose of nelfinavir rather than the 500 mg dose.

Results ? CD4+

By the 6th month of the study, the average CD4+ count had increased by about 150 cells among subjects receiving nelfinavir. Subjects on AZT and 3TC alone had an average increase of 104 cells by the 6th month.

Toxicity ? signs/symptoms

Side effects reported with nelfinavir at the 750 mg dose included:

* diarrhea 19%

* nausea 7%

* farting 3%

* rash 3%

* depression 2%

* vomiting 1%

Side effects reported with nelfinavir 500 mg included:

* diarrhea 12%

* farting 5%

* nausea 3%

* depression 2%

* vomiting 1%

* rash 1%

According to the researchers, the diarrhea associated with nelfinavir did not cause weight loss.

Toxicity ? lab tests

Increased levels of liver enzymes were seen in about 1% of subjects on nelfinavir (either dose) while high levels of triglycerides were seen in 2% of nelfinavir users on the 750 mg dose. According to the doctors, ?most [abnormal lab test results] were seen in [subjects] receiving AZT and 3TC alone.?

Drug resistance

Researchers found that about 6% of subjects developed HIV that was resistant to nelfinavir by the 4th month of the study.

Nelfinavir and saquinavir

In a study on 14 HIV-infected subjects (1 female, 13 male), doctors tested combinations of nelfinavir 750 mg three times daily together with the new soft-gel version of saquinavir 1200 mg three times daily with or without food.

Results

Half the subjects had a viral load of 40,000 copies and 327 CD4+ cells at the start of the study. Within several weeks, 60% had a viral load of less than 500 copies. Nelfinavir boosts levels of saquinavir 5 times higher than normal. A study of nelfinavir with saquinavir (soft-gel) taken 800 mg three times daily has been started in Canada.

REFERENCES:

1. Henry K, Lacarca A, Myers R and Chapman S The safety of Viracept TM (Nelfinavir mesylate) in pivotal phase II/III double-blind, randomized controlled trials as monotherapy and in combination with either d4T or AZT/3TC. Oral presentation, poster 240.

2. Kravcik S, Sahai J, Kerr B et al. Nelfinavir mesylate increases saquinavir-soft gel capsule exposure in HIV+ patients. Oral presentation, abstract 371.

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