TreatmentUpdate 70, Volume 8, No 6; September, 1996
Sean Hosein

Although saquinavir can reduce production of HIV in laboratory experiments, when taken orally more than 90% of the drug is not absorbed or processed, which drastically reduces the amount of drug that gets into the blood. As a result, researchers have been testing between 2 and 4 times the licensed dose of saquinavir (1800 mg/day) to see if absorption can be increased.

Study details

Researchers enrolled 40 HIV-infected subjects (1 female, 39 male) with CD4+ cell counts ranging between 188 to 527 cells, the average being 346. Sixteen subjects in each group had less than 3 months of exposure to AZT and "related" drugs. Half the subjects received "low-dose" saquinavir, that is, 3,200 mg/d. The other half received "high-dose" saquinavir, that is, 7,200 mg/day. The drug was supplied in 200 mg capsules, so some subjects "needed to take 36 [capsules] each day."

Results -- low dose saquinavir

* CD4+ cell counts

Subjects in the low-dose group had an increase of 72 cells by the 4th week of the study. By the 6th month of the study, this figure had fallen to 31 cells. The increased cell count was statistically significant until the 4th month.

* HIV

The amount of HIV in the blood fell to 1/12th its pre-study level by the 2nd week of the study. After that it began to increase until by the 6th month, it had returned to near its pre-study level.

Results -- High dose saquinavir

The average CD4+ cell count rose by 121 cells when subjects started using saquinavir. Six months later the average increase was 82 cells. These changes were statistically significant. Readers should note that all subjects in this group had an increase of at least 50 CD4+ cells. The difference in the increased CD4+ cell counts between the high-dose and low-dose groups was statistically significant in the 3rd and 5th months of the study.

* HIV

In the high-dose group, production of HIV fell to 1/22nd its pre-study level. After this, it began to increase slowly but still remained below its pre-study level by the 6th month. This difference between the level of HIV in the 6th month and the pre-saquinavir level was statistically significant.

Toxicity -- low-dose group

Common signs/symptoms included:

* fatigue

* headache

* muscle pain

* diarrhea

* low-blood sugar

Toxicity -- the high-dose group

Common signs/symptoms included:

* headache

* muscle pain

* diarrhea

* low levels of magnesium in the blood

According to the researchers, all subjects recovered from all of these effects once they stopped taking the drug. They added, "Most gastro-intestinal [problems happened during] the first 1 - 2 weeks [of the study] and decreased or disappeared.... without [need to reduce the dose]." Since subjects could tolerate the doses of drugs used in this study, the researchers think that further experiments with these doses of saquinavir and other antiviral drugs should be conducted. The company that makes saquinavir is also testing a new form of the drug in soft gel capsules. Researchers think that use of this product should result in much higher levels of saquinavir in the blood. In Canada that study in question is being coordinated at Sunnybrook Hospital (Toronto).

REFERENCE:

1. Schapiro JM, Winters MA, Stewart F, et al. The effect of high-dose saqunavir on viral load and CD4+ T cell counts in HIV-infected patients. Annals of Internal Medicine 1996;124(12):1039-1050.

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