Medical Advances with International Impact: Maternal Transmission; TB Prevention; Easier Sample Preparation Oral Contrace
Some recent advances can be particularly important for developing countries where about 90% of people with HIV live. Public support will be will be crucial in improving treatment access for more people. These issues are becoming more prominent during preparations for the 12th World AIDS Conference, June 28 - July 3 in Geneva.Simplified AZT Regimen Cuts
Maternal-Infant Transmission in Half
On February 18 the U.S. Centers for Disease Control and the Ministry of Public Health of Thailand announced that a short course of AZT can greatly reduce the risk of transmission of HIV from mother to infant. The simplified regimen used AZT orally twice a day for the mother, starting at week 36 of pregnancy and continuing through labor. The drug was not given to the infant. The women in this trial were not breastfeeding.
This result means that we now know that a regimen suitable for developing countries can prevent maternal transmission of HIV. The next step is to push to make the treatment available to all HIV-positive pregnant women who want it--as well as supporting the ongoing research to find better prevention methods, perhaps using more than one drug.
The AZT regimen now used in rich countries to prevent maternal transmission has been unworkable in much of the world, mostly but not entirely because of the cost. The conventional treatment starts much earlier, at week 26 of pregnancy--but in many countries women do not come in for care until shortly before delivery. The women take AZT five times a day for the rest of the pregnancy, and then intravenously during labor; in addition, the infant receives AZT orally for two months. The new regimen can be started late, avoids all intravenous treatment, uses twice daily dosing, and requires much less of the drug. However it was not as effective as the more extensive regimen, reducing transmission about 50% (from 18.6% without AZT to 9.2% with AZT in the Thailand trial), vs. almost 70% (25% without AZT to 8% with AZT, in the earlier trial in the U.S.).
The new report also ends the divisive dispute on use of placebos in trials to reduce transmission in developing countries. From now on the placebo arms will be dropped or switched to the short-course AZT regimen, now that it is known to work.
Mark Harrington of the Treatment Action Group called on Glaxo Wellcome to "make AZT available to developing countries for a substantially reduced price, or give the drug away for free, as Merck did with its drug for African river-blindness. Over 500,000 children are born with HIV each year. Short-course AZT could prevent infection in at least half of these cases, saving millions of lives in the next few years."
UNAIDS, which coordinated the international research effort which included the Thailand trial, will hold a meeting of interested governments and agencies in Geneva at the end of March, "to find ways of rapidly and effectively implementing the results of this and other trials into public health policy as they become known."
Tuberculosis Prevention: Faster Two-Drug Regimen Found Effective
A trial in almost 1600 people with HIV found that a two-month regimen with two drugs (rifampin and pyrazinamide) was as effective as the conventional one-year regimen of isoniazid in preventing development of active tuberculosis, in persons who were known to be TB-infected as determined by a positive skin test. The two-month regimen is easier and less expensive to administer; it also seemed to have better survival (5.8 deaths per 100 patient years, vs. 6.7), although this difference was not enough to be statistically significant, meaning that it could have occurred by chance. The two-month regimen is likely to be preferred in the U.S., but could be more important in developing countries where preventive treatment has not been widely used so far because of cost. HIV can greatly accelerate the development of tuberculosis, which causes about a third of AIDS-related deaths in the world.
About 70% of the volunteers in this study were in the U.S., enrolled through government research programs. Others were in Haiti, Brazil, and Mexico. The results were reported at the 5th Conference on Retroviruses and Opportunistic Infections (F Gordin and others, A Randomized Trial of 2 Months of Rifampin (RIF) and Pyrazinamide (PZA) Versus 12 Months of Isoniazid (INH) for the Prevention of Tuberculosis in HIV-Positive(+), PPD+ Patients (pts) (late breaker abstract #LB5].)
Dried Blood Spots Allow Simpler Test for Viral Load, Newborn HIV Infection
Dried blood spots--a well-known method of preserving blood samples for certain tests--may be useful in some cases for measuring HIV viral load. The advantage is that the samples do not need refrigeration, nor require a centrifuge or other special equipment or supplies that are unavailable in many settings. Also, much less blood is used, an advantage particularly for infants. Three studies on dried blood spots were presented at the 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998.
Viral load testing can be used to diagnose many HIV-infected infants in the first days or week of life, so that treatment can be started only for those who need it. The standard antibody test for HIV infection will not work until later, because all infants of HIV-infected women will test positive due to the mother's antibodies. One study suggested that samples can be pooled when screening for HIV infection, greatly reducing the cost of the testing, which could help in making medical care available to persons who otherwise would not receive it.
The three new studies are:
S Cassol and others, Dried Blood Spots (DBS) for Monitoring HIV-1 RNA Load in Neonates and Infants [abstract #315]. This study used two different viral load test kits, the Roche Monitor PCR vs. NASBA, to measure viral load in stored dried blood spots, and compared the results to those of conventional viral load measurements using liquid plasma, which had been run earlier for the same infants. It concluded that "HIV-1 RNA recovery in DBS is feasible, highly reproducible, and compares favorably with conventional liquid plasma measurement, making it suitable for use in large-scale international field trials."
AM Comeau and others, Use of Microsample Dried Blood Spot RNA Assays for Diagnosis of Pediatric HIV in the First Week of Life [abstract # 530]. Here the same team reported on tests of dried blood spots to diagnose HIV infection early after birth. The researchers concluded that "with slight modifications, RNA kits designed for viral load determinations can be used reliably on microsample DBS to detect the presence of HIV early in life."
AM Comeau and others, Quality-Controlled Pooling Strategies for Nucleic-Acid Based HIV Screening: Using PCR as a Primary Screen on Dried Blood Spot Specimens in Population Studies [abstract #318].
This study looked at pooling part of the material from dried blood spot samples, to reduce the labor and the number of test kits needed to screen for HIV infection. In this case, pooling means combining several samples for an initial test; if the batch tests negative, then all the samples are known to be negative, and if the batch tests positive, then all samples in that batch must be tested individually. This procedure, applied to stored blood samples from newborns in this research project, reduced the number of tests to less than a third of what would otherwise have been required.
