Preventing Mother-Infant Transmission Worldwide: What Is Needed? Interview with Joseph Saba, M.D.
Every year over 500,000 infants are infected with HIV from their mother, before or during birth or shortly after, and almost 500,000 children die. More than half of these infections and deaths could be prevented by treating pregnant women before birth. A recent clinical trial in Thailand showed that a less-intensive AZT regimen, suitable for developing countries, was effective. Two weeks later, Glaxo-Wellcome offered to reduce the price of the drug for treating pregnant women by up to 75%--an important step forward, as it brings the drug cost of the full regimen to as low as $50.But aside from cost of the drug, there are major logistical problems to making this treatment available. We asked Joseph Saba, M.D., Clinical Research Specialist with UNAIDS (the Joint United Nations Programme on HIV/AIDS), to explain what is needed now.
AIDS Treatment News: Give our readers a short history on antiretroviral drug treatment to prevent mother-to-infant HIV transmission.
Dr. Saba: Everything started in 1994 when the first results of the study ACTG 076--a clinical trial in pregnant women in the U.S. and Europe--showed that AZT started between week 14 and 34 of pregnancy and continued until delivery, and given after birth for six weeks to the baby, could very significantly reduce the risk of mother-child transmission. Following these results, the World Health Organization held a meeting in Geneva to see how they could be applicable to the developing countries.
It became clear that these results were not applicable in many countries, because the AZT regimen was long, and started before most women come to prenatal clinic in many developing countries; also, this regimen required intravenous treatment. It was logistically and financially impossible to implement in many developing countries.
So new trials were designed to test regimens that could be more widely used. One of these trials, sponsored by the U.S. Centers for Disease Control and conducted in Thailand, was completed in December 1997; the analysis was then done and results were announced in February of this year. This trial showed that transmission could be greatly reduced with a regimen which starts at week 36 of pregnancy, is given to women twice daily instead of five times daily the way the ACTG 076 regimen was, did not require intravenous treatment during delivery, and did not require treatment of the baby. So it is shorter and much easier to apply, and could work in developing countries. Other trials are now testing different regimens--without the placebo arms, which were stopped after the Thailand results became available. While these trials are ongoing we have been working on how to make any intervention that is applicable in developing countries really within the reach of these countries.
Several issues had to be addressed. How could the prenatal care system be adapted? What are the requirements in terms of voluntary counseling and testing? Will the women accept the intervention? And is it cost-effective, compared with other public- health programs?
We found that the treatment was acceptable; the women really wanted to use antiretrovirals to save their children from getting infected. Accepting the testing is a different issue, because it can result in discrimination, and then the women are afraid from their husband, or their family, or at their work. But once the testing has been done, they usually agree to take the medication.
When the Thai study results were announced, we adopted our cost-effectiveness model and found that this treatment was clearly cost effective--saving as many lives and sometimes more than the same investment in blood screening for HIV. It compares well to other public-health interventions.
Also while the trials were ongoing, we were in discussions with Glaxo-Wellcome. They were involved in these studies, and we continued discussion on how we could make the regime affordable to developing countries. You probably know about the Glaxo Wellcome announcement [on price reductions for AZT].
So as soon as we got the results, we were able to figure out how practical this intervention could be, and how applicable it is in developing countries.
ATN: What is needed now?
Dr. Saba: Last month in Geneva, a meeting hosted by UNAIDS in collaboration with WHO and UNICEF looked at the practical aspects, and the next steps now. This group decided to set up a mechanism to accelerate technical development and discuss the logistics with the countries interested in doing programs, to make this happen as quickly as possible.
ATN: To give people a sense of the overall size of the effort required, about how many women each year become pregnant who are HIV positive?
Dr. Saba: According to UNAIDS estimates, more than half a million babies each year are born with HIV infection, or acquire it early after birth, from mother-to-child transmission. So working from the HIV transmission rate, we estimate that between two and three million pregnant women are HIV-infected.
ATN: How many women will have to be tested to find them?
Dr. Saba: That depends on the HIV prevalence. In countries like Zimbabwe, where 35% of pregnant women are infected, you would have to test three times more. In countries where fifteen percent of the women are infected, seven times more women must be tested. In countries like Thailand, where the prevalence is 2.4%, you could compute similarly.
We modeled the cost effectiveness, and if the prevalence rate is very low, then maybe one should not use a program of mass testing and counseling, but either target settings where prevalence is higher, or focus testing on those women known to be exposed to HIV in one way or another. When the prevalence rate is over 5%, it may be more cost-effective to offer testing to everybody. We will need to test many more women than are HIV-positive--maybe 20 or 30 million--to provide this treatment worldwide.
There are major problems in reaching many of these women. In some countries, fewer than 60% of pregnant women attend prenatal clinics. Many come at least once for prenatal care, but they do not necessarily deliver; in some areas of Tanzania or Uganda, for example, as few as 30% of women who have come for prenatal care deliver at the hospital. The reason is usually just the lack of transport, the lack of a telephone, to get there. But many come to a clinic during pregnancy, so at this time we could consider giving them the antiretroviral treatment.
Making such a program available to all pregnant women who really need it will take a long time. First you need to reach the women who attend prenatal clinic--then the women who do not attend, which is difficult.
We need to look at this like the vaccine programs. This treatment is like a vaccine for the child, for preventing HIV infection in the child. When the expanded programs on immunization were established, it took years to be able to reach the whole population in a country.
ATN: Therefore this will be a long-term effort, working with the countries, and different in each country?
Dr. Saba. Yes, exactly. It is a long-term effort which needs to start now. We also must strengthen prenatal care; you need to have trained doctors and nurses, and have adequate care given to pregnant women, if we are to give them antiretrovirals.
And one must not forget about transmission through breast feeding, and the need to provide these women alternatives; this also requires logistics.
ATN: How can we approach the problem of violence and discrimination against women who test positive?
Dr. Saba: That is a very serious problem. There are basic principles. One must respect the choice of women to be tested and counseled. Also, this must be done in a very confidential way, with appropriate counseling. Confidentiality is essential because it will increase the credibility of the center in the testing process, and also it will help protect the women against any possible discrimination.
ATN: Are there programs in operation today where AZT is being delivered at a reduced price?
Dr. Saba: Not yet, but many countries are already designing programs, and some have contacted Glaxo Wellcome. We hope that within the next few months we will have programs ready to go in these countries. Thailand, for example, is very interested in implementing the process as quickly as possible; so is Zimbabwe.
ATN: What can our readers do, what can AIDS organizations within the United States do to help in this process?
Dr. Saba: It will be a lot of work for everybody--in designing programs, in helping the countries, helping the communities in these countries to take part in the process, and developing the advocacy messages that still need to go out. Now there is an increased momentum for this issue--for the access to drugs in general, and also for mother-to-child transmission. We need to keep this momentum growing, to turn the research findings into reality in developing countries.
A few years ago, when HIV blood screening was advocated, there were difficulties and restrictions and financial problems. Now the blood supply is screened in most countries. We need to keep driving this momentum. It is an effort for all of us.
