TreatmentUpdate 66, Volume 8, No 2; February 1996
Sean Hosein

Researchers enrolled 366 HIV-infected subjects (13% female and 87% male) whose CD4+ cell counts ranged between 200 and 500 cells. The average count was about 360 CD4+ cells. On average, about 70% of subjects had no symptoms of HIV infection. As well, between 11 and 20% of subjects had used AZT before entering this study, half of whom used it for less than 3 weeks. All female subjects were supposed to have pelvic exams and pap smears twice yearly. Subjects who had recovered from a life-threatening infection or cancer were allowed to enter the study provided they had recovered and no longer needed treatment for that infection or cancer. Researchers monitored 50% of subjects for between 10 and 12 months. In the first 6 months of the study, neither doctors nor subjects were supposed to know which subjects were receiving which drug (or combinations of drugs). Researchers randomly assigned subjects to one of four groups:

AZT; 600 mg/day 3TC; 600 mg/day 3TC; 300 mg/day and AZT 600 mg/day (low-dose group) 3TC; 600 mg/day and AZT 600 mg/day ( high-dose group)

Results CD4+ cell counts

At least half of the subjects in each group had the following increases in CD4+ cell counts during the first 6 months of the study:

AZT alone; 12 CD4+ cells 3TC alone; 24 CD4+ cells low-dose group; 66 cells high-dose group; 41 cells

One year later the figures were:

AZT alone; 32 cells 3TC alone; 33 cells low-dose group; 70 cells high-dose group; 65 cells

Production of virus

On average, for the first 6 months, at least half of the subjects in the combination groups had the amount of HIV in their blood decrease by 93% compared with their pre-study levels. Subjects receiving AZT alone had a 50% decrease, while for those receiving 3TC alone the figure was 75%. The differences between the [combination] groups and those receiving one drug were statistically significant. The reduced amount of HIV in the blood of subjects on combination therapy continued for 12 months.

Toxicity

Serious side effects occurred in 8% to 12% of subjects. Subjects receiving AZT alone or in combination were likely to develop side effects faster than subjects not taking AZT (alone or in combination). This difference was statistically significant, that is, not likely due to chance alone. Common side effects included:

gastrointestinal problems (including nausea) headache mild damage to nerves in hands/feet (peripheral neuropathy)

Side effects such as nausea, feeling tired, having low energy were severe enough to cause 23 subjects to leave the study. Two other subjects (both receiving AZT) left because of lower than normal levels of a particular type of white blood cell called neutrophils. Two subjects receiving AZT alone and one receiving 3TC alone died. Further details were not released.

Unanswered questions

Readers should keep in mind that 70% of subjects in this study had either not used AZT or had had little exposure to AZT before entering this study. Results may be different in other subjects who had never used AZT for more than 3 weeks.

While the results from this study, which suggest greater benefit is possible with a combination of anti-HIV drugs, researchers are not certain that:

the combination of study drugs can reduce the risk of developing a life-threatening infection/cancer; the rise in CD4+ cell counts in the blood reflects production of new cells or merely a redistribution of cells from lymph nodes and tissues; the increased number of CD4+ cells are fully functional to provide the protective immunity needed to resist many of the infections seen in AIDS; the bone marrow can withstand long-term treatment with the study drugs.

REFERENCES:

1. Eron JJ, Benoit SL, Jemsek J, et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimetre. New England Journal of Medicine 1995;333:1662-1669.

2. Merrigan TC. A quarter-century of antiviral therapy. New England Journal of Medicine 1995;333:1704-1705.

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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