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A Call to Action

At Long Last We Have an Inexpensive, Effective Means of Reducing Vertical Transmission of HIV. Now We Need a Coordinated Global Effort to Ensure That This Intervention Is Made Available to Pregnant Women Everywhere

February 2000

These are the best of times -- and the worst of times -- for everyone who is engaged, however peripherally, in the worldwide effort to reduce the vertical transmission of HIV infection. These are the best of times because, in the developed world, we have succeeded in reducing perinatal transmission by as much as 75% -- and because, at long last, we have at our disposal an inexpensive and effective means of preventing a significant number of the HIV infections that occur when seropositive women in Third World countries give birth. These are the worst of times because, at present, the women who are most likely to give birth to infected infants are also the women least likely to have access to the safe, simple, single-dose drug regimen that has been shown to reduce the rate of maternal-to-infant HIV transmission by as much as 50%.

In the absence of chemoprophylaxis, vertical transmission occurs in between 14% and 40% of live births to HIV-infected women -- with the viral burden of the mother being the most important correlate of the rate of infection. A number of recent studies have concluded that mothers who have high viral loads are more likely to transmit the virus, but this is clearly not the only factor affecting mother-to-infant transmission, because we know that women with exceedingly high viral loads and double-digit CD4 counts have delivered healthy, uninfected children -- and women with undetectably low viral loads and mid-range CD4 counts have given birth to HIV-infected offspring.

Unfortunately, there is no absolute guarantee that an HIV-positive woman -- even one with a near-normal CD4 count and no detectable viremia -- will deliver an uninfected baby. Even in the best of circumstances, some risk remains -- which is why we routinely recommend that all seropositive women receive antiretroviral therapy during pregnancy (see "Antiretroviral Therapy in Pregnant Women," Vol. 3, No. 4). The purpose of this therapy is two-fold: to reduce the risk that the babies will be born HIV-positive, and to optimize the health of their mothers.

We have known since 1994, when the striking data from the landmark clinical trial ACTG 076 were published, that the administration of zidovudine to pregnant HIV-infected women reduces by two-thirds the likelihood that these women will transmit the virus to their babies, assuming the women do not breast-feed their infants. Indeed, the dramatic results of this trial were described in the second issue of HIV Newsline (see "AZT Diminishes Transmission of HIV-1 from Mothers to Their Infants," Vol. 1, No. 2, pages 31-35). Over the last six years, the rate of vertical transmission of HIV in the United States has dropped from 25% to between 8% and 3%, thanks to countrywide efforts to encourage all pregnant women to agree to HIV testing, coupled with culturally-specific counseling programs designed to encourage all women who do test positive for HIV to agree to take antiretroviral agents during pregnancy and delivery.

Two years ago the National Institutes of Health released the results of a retrospective meta-analysis that included 8,533 infants born to HIV-positive mothers. The data revealed that when women who were given ZDV during pregnancy were delivered by cesarean section, the rate of HIV transmission was reduced to 2% (range: 0.0% to 4.0%) -- a significant improvement over the transmission rate of 7.3% (range: 5.9% to 8.8%) for HIV-positive mothers who took ZDV but delivered their new- borns vaginally.

Several subsequent studies have reaffirmed the N.I.H. finding that seropositive women who deliver by cesarean section are less likely to transmit the virus to their newborns than women who deliver vaginally. However, it appears that this benefit is seen only in cases of elective C-section -- that is, when the surgical procedure is undertaken prior to the onset of labor and the rupture of the uterine membranes. To further complicate matters, the only prospective, randomized trial of elective C-section in HIV-positive women taking ZDV failed to show a statistically significant reduction in vertical transmission in the cohort assigned to surgery. Moreover, no studies have yet assessed the value of C-section in women on multidrug antiretroviral therapy. (For further information on the risks and benefits of elective cesarean section for seropositive women, see "C-section further reduces risk that mothers with HIV will pass the virus to their newborns," AIDS Care, Vol. 2, No. 4.)

As we enter the twentieth year of the HIV pandemic, it is reasonable to anticipate that the HIV transmission rate will be 5% or less among seropositive pregnant women who receive ZDV monotherapy -- and this modest risk may eventually be all but eliminated in women who respond well to combination therapy. To whom do these encouraging statistics apply? Almost exclusively, to women who receive antenatal care, are offered HIV counseling and the option of voluntary testing, and can obtain antiretroviral therapy. The vast preponderance of these women live in the developed countries of the world or have access to medical care in those countries.

These lucky women, these happy few, represent only a tiny fraction of the world's population of 20 to 25 million seropositive females -- 80% of whom live in sub-Saharan Africa, where infection rates in the worst-hit areas approach 40% and where, by the year 2010, some 40 million children will have been orphaned by the HIV epidemic. For most of the women in sub-Saharan Africa and other developing countries, the ACTG 076 regimen is not an option, and even the short-course ZDV regimen that was developed specifically for Third World countries may not be an option -- because most of these women receive no antenatal care and deliver out of hospital, so there is no opportunity to provide them with HIV counseling and testing, nevermind chemoprophylaxis to prevent vertical transmission.

South of the Sahara, where condoms are costly and the family finances are usually controlled by men, birth control and barrier protection are frequently not among a woman's options. And of course bottle-feeding, which requires expensive formula and a safe water supply, is also not an option in many places -- which means that a certain percentage of the infants who are born seronegative to seropositive mothers will be infected at their mothers' breasts. Studies suggest that 15% of these babies are infected through breast-feeding.

For these vulnerable women, nevirapine does provide an option. As a pivotal study conducted in Uganda has elegantly demonstrated, a single dose of nevirapine, given during labor, plus a single dose of nevirapine syrup, given to the neonate within three days of birth, is at least as safe as ZDV and reduces vertical transmission by 50% (see "A safe, effective, and inexpensive means of interrupting vertical transmission of HIV," on pages 7-8 of the newsline section of this issue). Moreover, the cost for the two doses of nevirapine is only $4, versus $819 for the ZDV monotherapy regimen that has been the standard of care in developed countries ever since the data from ACTG 076 were published six years ago.

Here, at long, long last, is what healthcare providers, public-health officials, and AIDS advocates have been clamoring for: a remarkably safe, remarkably inexpensive, and remarkably effective means of preventing mother-to-infant transmission of HIV infection. A perfect chemoprophylactic agent would be 100% safe, 100% effective, and would cost less than 26¢ -- which is what Uganda spends per capita per year on health care. This regimen falls short of perfection, as all such regimens do, but its low cost and high efficacy have encouraged and excited those of us who are involved in the global effort to slow the rate of vertical HIV transmission.

Getting this desperately needed prophylactic agent into the hands -- and into the mouths -- of the women and children who most need it is going to be no easy task. As the authors of the Ugandan study point out, half of the women in sub-Saharan African who are potential candidates for single-dose nevirapine intervention live in remote regions that are unserved by any kind of healthcare providers -- so we will have to find ways to deliver the drug to these women. To do that, we will have to overcome cultural as well as logistical hurdles. In order to be given a chance to help these women, we will have to persuade them that our Western medicine can help them.

No one imagines that this is going to be an easy task -- but no one can deny that it is an urgent and essential one. If the suffering of these desperate, destitute, defenseless women and their infants is not enough, in and of itself, to galvanize the world's attention, then the specter of 40 million AIDS orphans, indigent and ignorant, often homeless and hungry, should spur the world to action.

To provide both an incentive and an example, the Elizabeth Glaser Pediatric AIDS Foundation has pledged $1,000,000 in seed money to launch an initial intervention campaign. In partnership with Global Strategies to Prevent Perinatal Transmission we have also issued a call to worldwide action -- to save the lives we can save, using the tools we now have.

This call is directed at pharmaceutical companies. We call on them to assist, directly and indirectly, with the cost of implementing programs to reduce the number of babies born HIV-positive. Noting that several drug companies have received worldwide acclaim for donations of drugs to cure other diseases in poor nations, we call on all companies to respond to the human need in the HIV epidemic.

This call is directed at multinational corporations. We call on them to assist in setting up public information and education programs and in the registration and delivery of drugs. They can help spread both the knowledge and the simple means to save babies' lives. We also call on them to contribute, both for the good of their future markets and for the good of the world.

We call on religious groups, public and private charities, large and small foundations, and nongovernmental organizations to take the lead in this vital crusade -- because partnerships between the public and private sectors can expedite the implementation of intervention programs.

Our call for action is immediate. A new baby is infected with HIV every minute of every day. Half of those infections can be prevented, and therefore all delays should be measured in those terms. With an investment of $10,000,000 immediately, we can begin to prevent some of the estimated 600,000 HIV infections that occur in children each year. The Elizabeth Glaser Pediatric AIDS Foundation is seeking commitments of at least that much money in the next few months.

"I'll get back to you in a couple of days" means that 2,400 babies will be infected who need not have been. "When the review committee meets in a month" means that 35,000 babies will be infected who need not have been. "When the U.S. Congress returns in January" means that 112,000 babies will be infected who need not have been. "Not until the patent expires" means that millions of babies will be infected who need not have been.

We call for the world to recognize its obligation to prevent HIV infection in babies -- and to do so today.

Catherine M. Wilfert, M.D., is Professor Emerita, Department of Pediatrics, Duke University Medical Center, Scientific Director, Elizabeth Glaser Pediatric AIDS Foundation.

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This article was provided by San Francisco General Hospital. It is a part of the publication HIV Newsline.