On the eve of the opening of the 12th World AIDS Conference in Geneva, the American Medical Association held a day-long briefing on the research presented in the July 1st, "all-HIV" edition of JAMA
. The briefing allowed the researchers whose work is being published to present information in lay terms to the press and public. Two key presentations covered:
Simultaneous vs. Sequential Initiation of Therapy with Indinavir (Crixivan), Zidovudine (AZT) and Lamuvidine (3TC) for HIV Infection: 100 Week Follow-Up
Roy Gulick, MD, MPH, Assistant Professor of Medicine, Cornell University Medical College, New York
Coverage by Michael Giordano, M.D.
At the last international AIDS conference in 1996 in Vancouver, Dr. Gulick presented early (24-week) data from this study of AZT, 3TC and the protease inhibitor indinavir (Crixivan) that showed the world how encouraging triple combination therapy could be. Now, this study of 97 patients has the longest follow-up to date of a combination HIV drug regimen.
This important presentation of two-year data from the study (known as Protocol 035) included the following points:
- patients who started indinavir, AZT and 3TC all at the same time (simultaneous therapy) had the best results -- 78% of those patients maintained HIV levels below the limits of detection (<500 copies/mL) for 100 weeks. Side effects were limited and manageable
- patients on the triple combination arm experienced a rapid initial rise in CD4 (T) cell counts over the first 3 months on the study, and their T-cells continued to increase steadily throughout the study.
- most patients with undetectable levels of HIV by week 24 on the antiretroviral regimen of indinavir + AZT + 3TC will have continued "undetectability" through at least 100 weeks of follow-up
The study also taught important lessons on how to use antiretrovirals in combination. Patients who started with simultaneous therapy (i.e., starting all the drugs at the same time) had a significantly better chance of reaching undetectable than people who started the three drugs sequentially (adding one drug after another over time). Adding the drugs one at a time over several months kept HIV undetectable in only 30% - 45% of patients for 100 weeks. The study concluded that using drugs sequentially is a major cause of the treatment failure that has been reported increasingly in the medical and popular media. This study should encourage doctors and patients to learn to use potent drugs like indinavir in combination therapy properly, in order to gain maximum benefit from them.
Perinatal HIV-1 Transmission: Interaction between Zidovudine Prevention and Mode of Delivery in the French Perinatal Cohort
Laurent Mandelbrot, MD, of Hopital Cochin-Port Royal, Paris
Coverage by Michael Giordano, M.D.
In this study of 2,834 pairs of mothers and infants, this French study team found that HIV-positive pregnant women may have the best chance of preventing transmission of HIV to their baby by having an elective cesarean section (before the beginning of contractions and labor), using AZT while pregnant, and receiving intravenous AZT during delivery.
This study found that:
- 17.2% of women who did not receive AZT transmitted HIV to their babies
- 6.4% of women who did receive AZT transmitted HIV to their babies
- only 0.8% of women who received and had an elective 'C-section' transmitted HIV to their babies
Earlier studies conducted in the United States have shown that AZT use during pregnancy does reduce the likelihood of HIV transmission from mother to child. The analysis of this study suggests that C-section and AZT therapy complement each other by protecting the baby at various stages of the gestation and birth process: during pregnancy, during the beginning of labor, and during delivery, when a great deal of blood is often present.
This study pointed out that a C-section is still major surgery, and may pose a significant risk to the mother, but it is a remarkably effective option that HIV-positive women who want to have a child may wish to discuss with their obstetricians.