Important note: Information in this article was accurate in October 2001. The state of the art may have changed since the publication date.
American Foundation for AIDS Research, October 2001
Anne-christine d’Adesky
In much of the world, the stork is regarded as a symbol of fertility, a welcome bearer of the good news that a baby is on the way, gently carried along in the stork’s beak. Not so in the capital of Uganda, where the giant marabou stork with its huge black wings and pink gullet is viewed more as a Grim Reaper, a symbol of death and decay, not life and prosperity. These large creatures are all over the capital, perched ominously like vultures in the trees, atop giant construction cranes, on telephone wires. They even alight on cars parked at the side of the road and fly so low that residents instinctively duck when one goes overhead.
A scavenger, the marabou began arriving here in the mid-1980s to feast upon piles of refuse that built up during two decades of civil war, including the successive reigns of Milton Obote and his notorious protégé, dictator Idi Amin, who ruled from 1971 to 1986. Up to a million Ugandans were murdered during this terrible period, their swollen bodies lining the grassland shores of Lake Victoria where the marabou like to nest. Many others lost their homes and livelihood, dying of hunger and disease. These included the first cases of AIDS, which was then called "slim disease" from the rapid weight loss that it triggered.
By the time current president, Yoweri Museveni, took power in 1986, Uganda was politically, economically and socially in tatters. It also was reeling from a fast-moving HIV epidemic. Like the marabou stork, HIV flourishes in settings of extreme poverty and civil instability.
Ask around the capital city, Kampala: Few families are untouched by HIV and AIDS. The situation is worst in the countryside, where entire villages have perished. The high AIDS death toll has affected not only the poor, but a wide swath of society, including professionals of all stripes, soldiers and policemen.
AIDS has in particular attacked women and their children. National infection rates are twice as high in women than men in their early twenties. And teenage girls aged 15 to 19 are deemed four to six times more likely to have HIV than boys – a trend reported in other parts of sub-Saharan Africa. Uganda bears the sad distinction of having more AIDS orphans than any other country in sub-Saharan Africa, with an estimated 1.7 million children who have lost one or both parents. Many of these children are also HIV-positive.
Given this stark picture, it is rather surprising to find Uganda viewed today as a model of success in HIV prevention, as well a litmus test of what more can be achieved by hard-hit African nations battling AIDS. In 1992, 16 percent of Ugandan adults were estimated to be HIV-positive; by 1996, that number had fallen by half. Newer statistics show an HIV prevalence rate of 6.1% for 2001. Credit must go to the government’s National AIDS Control Programme, set up by the Ministry of Health, which has emphasized mass education about HIV and condom use, as well as voluntary counseling and testing (VCT). Although AIDS remains highly stigmatized and feared, polls suggest there is a broad awareness of the disease and the ways it can be contracted. Such awareness remains more common in Kampala than in the countryside.
The national picture remains very sobering. In a keynote address at the recent African Great Lakes Conference on Access to HIV AIDS Care and Support, leading HIV researcher Peter Mugyenyi noted, "The current HIV rate is unacceptably high and appalling and would constitute a state of emergency in developed countries." One million Ugandans are infected by HIV, and they have limited access to antiretroviral medicines. Mugyenyi predicted, "New infections will continue to spread from the huge infection reservoir, most of who do not know their serostatus." That includes a large number of women who are passing HIV on to their offspring. The Ugandan government has found that the present rate of mother-to-child HIV transmission is 28%. Out of a million live births per year, 100,000 test HIV-positive, according to Dr. Laura Guay of Johns Hopkins University and Makerere University in Kampala.
The government last year announced a major national program for the prevention of mother-to-child transmission (PMTCT) of HIV using anti-HIV drugs like AZT and nevirapine. By 2004, it hopes to offer all pregnant women attending government clinics a comprehensive package of voluntary HIV counseling and testing (VCT), maternal care and STD prevention, and for those who test HIV-positive, a PMTCT regimen. The services offered will also include antimalarial and antiparasitic treatment.
The program will utilize two PMTCT regimens. The first is "short-course" AZT. AZT will be administered to pregnant women from the 36th week of pregnancy until a week after delivery, with a liquid dose of AZT for the newborn. The alternative regimen is a single dose of nevirapine to a mother going into labor and a single liquid dose for her baby within 72 hours after delivery. Both regimens are deemed safe for mothers and infants. Combined with an effective counseling and testing program, they have proven quite effective in reducing maternal transmission. The groundbreaking HIVNET 012 study done in 1997 at the antenatal clinic in Kampala’s Mulago Hospital, for example, showed that nevirapine can reduce MTCT by 50%.
The Ugandan PMTCT program is backed by a five-year donation of free nevirapine from the German manufacturer, Boehringer-Ingelheim. Additional financial support has come from the Gates Foundation and the United States Agency for International Development (USAID), among others. The first reports show that implementation of the program is steady. But serious barriers have emerged that raise concerns about the PMTCT effort’s ultimate ability to protect babies from HIV.
In a nutshell, the government’s strategy consists of integrating the PMTCT program into the admittedly weak national health infrastructure of government hospital, family planning and rural antenatal clinics where voluntary counseling and testing services are already offered. Currently, only a half-dozen government hospitals in Uganda offer VCT, so the new program provides an opportunity to build up the national health infrastructure. The PMTCT sites are initially limited to several in Kampala district, including Mulago Hospital, which is the largest medical center in the country, and hospitals in Galu and Arua districts. By early next year, the government expects all districts to have sites up and running.
Since only 40 percent of Ugandan women are estimated to deliver their infants in hospitals — the remainder in private clinics or at home with midwives — the number of pregnant women seeking care from the public sector should increase. There is also early talk of using the PMTCT program as a springboard for future introduction of long-duration anti-HIV therapy, a concept called PMTCT-Plus.
At September’s 3rd International Conference on Global Strategies to Prevent Maternal to Child Transmission in Kampala, Dr. Saul Onyango, the director of the PMTCT program, reported that 19,700 pregnant women have been counseled for HIV in the hospitals that now offer VCT and that over 70% accepted testing. Of that number, 2,026 were HIV-positive. Onyango said, "Our biggest encouragement is that after one year of implementation, almost 20,000 mothers know their serostatus. That is a good starting point. We hope they can bring their friends and peers aboard, but also get into services."
Given Uganda’s limited national health budget of $12 per person, the PMTCT program represents a major investment. In addition to counseling and testing, an antiretroviral regimen, and monitoring and treatment for STDs, pregnant women are given vitamin A, folic acid and iron supplements to maintain their health. "Mother and infant will also be followed during the first two years of the baby’s life. All of this is costly," Onyango noted. "Coordination, training, sensitization, putting in supplies, monitoring, evaluating the whole program — all of these must be put in a system that is very weak. Community education, mobilization and sensitization is another challenge." As he sees it, implementation will be relatively simple in urban areas where there is some infrastructure, but harder in remote areas where clinics lack even basic medicines, equipment and enough doctors. This is partly due to a government policy of decentralization of the health sector, which has resulted in "cost sharing," bureaucratic red tape and competition for scarce funds.
A key component of the government program is a clear-cut recommendation that HIV-positive mothers either exclusively breast-feed or exclusively use replacement formula for the first six months, then immediately wean their infants to solid foods. That advice is based on a review of current trial data presented at the Global Strategies meeting by co-chair Dr. Francis Mmiro. Mmiro found that mixed feeding — occasionally replacing breast milk with formula, soft porridge or other foods — is linked with a higher risk of HIV transmission through breast milk than either exclusive breast- or bottle-feeding. Mixed feeding also carries with it a higher rate of infant mortality.
There’s plenty to worry about. Dr. Anna Coutsoudis of the University of Natal in Durban, South Africa estimated that, based on studies to date, the overall risk of MTCT through breast-feeding is 15% if a baby is breast-fed for two years. The infection rate over the first six years is not known. Out of 700,000 children worldwide who contract HIV through MTCT, up to half acquire it through breast-feeding, Guay estimated.
Amsterdam researcher Joep Lange and colleagues conducting the PETRA PMTCT trial in Uganda, South Africa and Tanzania presented preliminary results at the Global Strategies meeting. These clearly show that the initial benefits of using anti-HIV drugs to prevent maternal HIV transmission are lost over time due to postpartum transmission through breast milk.
The PETRA study compared three PMTCT regimens to placebo. Arm A consisted of short-course AZT-3TC at week 36 through labor, with postpartum AZT for mother and infant; Arm B tested AZT-3TC during labor and postpartum for infant and mother; and Arm C used AZT-3TC only during delivery. (A placebo arm was stopped in September 1998 when it was clear that AZT worked well to reduce MTCT.) Arms A and B were both effective at first in reducing MTCT whereas Arm C was not very effective. Lange remarked that "very little benefit remained after 18 months" with any of the regimens. In short, PMTCT was failing due to transmission through breast-feeding. (See table for the latest PETRA trial data.)
Infant formula represents the safest option to avoid exposure to the virus, but it is not always practical for mothers. Many are poor and cannot afford formula, which also requires preparation and clean water. In such cases, it may be safer for the infant to be exclusively breast-fed. Breast milk is more sterile and provides more complete nutrition than its alternatives. Research suggests that mixed feeding leaves the infants more vulnerable to GI tract infections and to HIV, which takes advantage of inflammation in the lining of the digestive system. The exclusive breast-feeding recommendation is somewhat controversial in itself, but the real problem is that many mothers cannot adhere to it. The obstacles are varied, a major one being fear of revealing HIV status.
Dr. Michele Magoni is an Italian HIV doctor who oversees one of the Ugandan PMTCT facilities. He said, "We opened a [PMTCT] site and there the test kits are available, but only 10% of the women are tested and go there for antenatal counseling and so few receive the testing. At the end of the day, almost none have received the prophylactic treatments."
The problem, his team realized, was its failure to address women’s fears of disclosure and its consequences. Magoni remarked, "In the first year and a half of activity, we did not move enough on community mobilization because it was a pilot project. We have to deal with the stigma."
A pilot PMTCT program in Abidjan, Ivory Coast revealed other barriers besides fear of disclosure, including difficulties with staff or clinic procedures, disbelief of HIV results, and doubts about AZT’s efficacy. In Uganda, few people know much about anti-HIV drugs, including nevirapine. Limited educational material is available in local languages, and illiteracy is high in rural areas. Pregnant women worry about taking drugs that might cause problems for the fetus or unknown side effects. When they do learn about nevirapine, they wonder about drug resistance and efficacy. Fortunately, PMTCT studies to date show there is only temporary drug resistance to prophylactic nevirapine, and it does not have a negative clinical effect on either mothers or infants.
"Are women going to be able manage MTCT?" asked Milly Katana, an outspoken HIV-positive activist with the grassroots National Guidance and Empowerment Network (NGEN), one of several networks for people living with HIV. "Some will, but not all, and I fear it won’t be easy. I think many of the women would choose formula if they could, because they don’t want to risk passing on the virus," she said. "But first of all, is formula going to be available for free for that whole time? Look at the problems we have just in getting other things. Also, it is difficult for women who have to go to work, or poor women who are in the bush, to use formula because it requires cooking equipment. They won’t always be able to keep it up without a lot of support."
The issue is more than the costs of exclusive bottle or breast-feeding. "Already," Katana said, "the women are expressing fears of rejection should they openly declare their HIV status, and health workers say the women are afraid that the [PMTCT] treatment will stigmatize them." Such fears were openly discussed at a women’s satellite meeting during the Global Strategies conference, where many HIV positive women admitted they hid their status from their husbands and partners. To them, being forced to adopt an exclusive feeding choice means having to explain why. "Women come back from these antenatal clinics and are blamed for bringing HIV into the home," said Jane Nabalonzi, a member of the Society of Women and AIDS in Africa (SWAA). "They are afraid their husbands will beat them, or kick them out of the house. So here we are asking them to do something to protect their baby that makes them vulnerable."
Another problem is that the recommendations are seen by many as foreign. "Culturally, we have the habit of mixed feedings in Uganda, and we supplement with porridge and other things. So this is something new that must be adopted," Katana explained.
Early results from the pilot PMTCT feasibility study at Nsambya hospital in Uganda do not ease her concerns. There, a short course of AZT and nevirapine was offered to women who tested positive late in their pregnancy. Out of 462 HIV-positive women, 240 accepted a PMTCT regimen and 198 had delivered their infants by the time of the Global Strategies conference. One hundred sixty-two women received AZT and 78 nevirapine. At week 6 post-delivery, 63% of the treated mother-infant pairs returned for follow-up care; at week 14, that number fell to 44%; and at month 28, it dropped to 8%. That makes it hard to know what the transmission rates are after birth.
One suggestion for avoiding the disclosure issue is to distribute PMTCT medications to all pregnant women, regardless of their HIV status. This is an idea pioneered in Tanzania by Axios International, a public health technical assistance organization. Despite covering all pregnant women, the universal approach saves money by sidestepping HIV counseling and testing. Activists and even Onyango point out that there are ethical problems inherent in indiscriminately distributing medication. This approach also ignores the critical role counseling and testing play in prevention and in helping women access care. It clearly leaves the baby vulnerable after birth.
HIV-positive women have a better idea: Why not treat them with anti-HIV drugs? "What’s the point of saving the child if it’s just going to become an orphan?" asked Cissy Ssuuna, an openly HIV-positive nurse and VCT counselor at Mulago Hospital. "Why don’t they care about keeping us alive and healthy so we can give our children a future? It may be cheaper to use nevirapine, but not if the parents die." As she noted, studies show that three-drug regimens given to pregnant women can lower viral load and effectively prevent any transmission to the fetus. They keep protecting the infant after birth and help the mother. Treatment also lowers the risk of sexual transmission.
Government officials don’t disagree with the science, but they cite the prohibitive cost of anti-HIV combination therapy and Uganda’s weak infrastructure as real obstacles to adult treatment. Still, the momentum is building for "PMTCT-Plus." PMTCT-Plus would provide for long-term treatment of mothers. For now, though, the government is looking at medical means to protect the newborn. Ugandan pediatric PMTCT clinical trials are under way that provide infants with nevirapine for up to 24 weeks after birth. Uganda is also proposing a neonatal HIV vaccine trial, the first such trial outside of North America.
On a social level, the Ministry of Health is focusing on community mobilization to sensitize people about HIV. It hopes to involve HIV-positive advocates like Katana and Nabalonzi to do peer education and set up support groups to help women manage safer feeding options. Speaking at the Global Strategies women’s satellite, Onyango urged participants to become key players, along with their spouses. He asked, "Can some of you people be lay counselors, so we can increase the number of people actively involved in the program? You are the ones who can reach these women and their partners."
As Onyango stressed, "Getting to the spouses is a real challenge." The PMTCT program will now actively target men by encouraging partners of HIV positive women to come to the antenatal clinics, traditionally a province of women and their infants. Pre- and post-test counseling will be offered to both partners, in order to help families confront issues around disclosure.
The nod to men and their role reveals a hard lesson the government has already learned. Success in PMTCT is not going to be a simple matter of providing pills or counselors. It requires tackling deep-seated gender dynamics and empowering women to have more control over their lives.
"The husbands are a real problem," acknowledged Nabalonzi. "Many husbands have two wives, and sometimes these wives do not even talk to each other about HIV, even if one of them is HIV-positive. They cannot afford to tell their husbands. That is the reality we are going to have to confront."
The women’s HIV networks are moving quickly on that front. In October, a new coalition was announced called the Women’s Treatment Action Group (W-TAG). Led by HIV-positive women, it plans to push not only for access to PMTCT and PMTCT-Plus, but, as Nabalonzi says, for more input into the national agenda. "We love our children here in Uganda," she remarked in summary. "As mothers and as women, we are going to have to fight, and fight hard, not just for our own survival, but for our families and our communities. We have no other choice."
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Copyright © 2001 by the American Foundation for AIDS Research (amfAR) and first displayed on amfAR's Treatment Directory web site (http://www.amfar.org/gl). They appear on AEGIS with amfAR's permission. Organizations wishing to reprint or redistribute these materials should request authorization from amfAR's Department of Treatment Information Services (212/806-1600).
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