TreatmentUpdate82 - Vol. 9, No. 8 - pp. 2-3; October 1997
Sean Hosein

Doctors recruited over 1,000 PHAs for this study to compare the effects of triple therapy -- indinavir with AZT (or d4T) and 3TC -- against double therapy with a combination of two nukes -- AZT (or d4T) and 3TC. PHAs receiving triple therapy had their risk of developing AIDS or dying fall by 50% compared to PHAs receiving double therapy. This study confirms the benefit doctors have seen in some of their patients who use protease inhibitors.

Study Details

Doctors reported data on 1,146 PHAs who had an average of 87 CD4+ cells and viral loads of at least 100,000 copies for this study. About 17% of subjects were drug users, 16% female and 3% hemophiliacs. At least half the subjects had used AZT for nearly 2 years before entering the study. Subjects were assigned at random to receive either (a) indinavir 800 mg/8 hours, AZT 200 mg three times daily (or d4T 30-40 mg twice daily) and 3TC 150 mg twice daily or (b) fake indinavir (placebo), AZT (or d4T) and 3TC at doses used in group A. For various reasons during the course of the study subjects would leave, so researchers were able to monitor only 50% of subjects for 10 months.

Results: AIDS

Nearly 100 subjects developed AIDS and/or died during the study:

* triple therapy: 6% developed AIDS or died

* double therapy: 11% developed AIDS or died

Common infections (61% of cases) were PCP (Pneumocystis carinii pneumonia), CMV (cytomegalovirus) and MAC (Mycobacterium avium complex).

Results: CD4+s and viral load

Generally, subjects on triple therapy had greater average increases in CD4+ cell counts -- as many as 121 extra cells -- at all times during the study than subjects on double therapy who, at most, had an average increase of 40 cells. These differences were statistically significant; that is, not likely due to chance alone. The increased cell counts were maintained by both groups for an average of 40 weeks.

Results: levels of HIV

Among those receiving double therapy, the level of HIV in their blood fell to no lower than 1/10th its pre-study value. For subjects on triple therapy, viral load fell to 1/1,000th its pre-study level by the 6th month of the study. Throughout the study, viral load in subjects on triple therapy remained lower than in subjects on double therapy. When doctors looked at subjects according to their CD4+ cell counts, those subjects who had 50 or fewer cells experienced a decrease in viral load to only 1/100th of their pre-study value.

Toxicity

Slightly more side effects were reported by subjects on triple therapy (21%) than by subjects on double therapy (18%). Commonly reported symptoms were:

* tiredness

* fever

* headache

* nausea and vomiting

More subjects on double therapy had low levels of a type of white blood cell neutrophils than did those on triple therapy. On the other hand, more subjects on triple therapy than those on double therapy experienced:

* high levels of bilirubin in the blood

* kidney stones

* kidney damage/dysfunction

* diabetes

This is not surprising as these problems are associated with the use of indinavir (kidney problems) and other protease inhibitors (diabetes).

Drop-outs

Overall, 20% of subjects left the study before they developed any illness or drug toxicity -- 12% in the group receiving indinavir and 28% in the group receiving double therapy. This difference was statistically significant. Over half the subjects leaving the study apparently did so because they wanted to receive indinavir and/or because of increasing viral load levels which they had measured outside of the study.

On the whole, triple therapy with indinavir reduced the risk of death or of developing AIDS compared to double therapy in PHAs with less than 201 CD4+ cells. Questions not answered by this study include:

* How long will the benefit from indinavir last?

* Will the amount of side effects increase over time?

* Which drug regimen can PHAs expect to receive benefit from once HIV has become resistant to indinavir?

REFERENCES:

1. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4+ cell counts of 200 per cubic millimetre or less. New England Journal of Medicine 1997;337(11):725-733.

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Copyright © 1997 - 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