Important note: Information in this article was accurate in October 2000. The state of the art may have changed since the publication date.Scientists and doctors are confident that they now know how to prevent most cases of mother-to-child transmission of the HIV virus during delivery, but a number of factors make it very difficult to do so in resource-limited settings. Furthermore, preventing transmission at the time of birth does not guarantee that the child will remain free of HIV infection.
"In the developed world, in countries such as the United States, HIV-positive mothers are advised not to breastfeed," said Subhasree Raghavan (Columbia University, New York), speaking in a July, 2000, interview. "The vast majority of them have access to clean water, heating facilities and formula, and thus most mothers are able to meet nutrient requirements of the babies using safely prepared bottle feeds."
But it is another story in resource-limited countries, said Raghavan. "In the developing world, mothers have a lack of access to heating facilities, safe water and formula. That leaves breastfeeding as [the] only viable and safe option for feeding babies. Thus there is an urgent need to work on methods and techniques that can make breastfeeding safe in these parts of the world."
Raghavan also called attention to another crucial difference: HIV-infected pregnant women in wealthier settings have a much greater chance of lowering their viral loads with antiretroviral therapy. Lower viral loads among HIV-infected pregnant women have been associated with lower rates of mother-to-child transmission (MTCT).
"However, it is a major challenge to take care of maternal health in the developing world due to unknown HIV status and due to lack of access to adequate nutrition, medical care, simple therapies for opportunistic infections and antiretroviral therapy," Raghavan said.
According to the US Centers for Disease Control and Prevention (CDC, Atlanta), in the absence of preventive drug treatment, there is a 25 to 30 percent chance that a woman will infect her newborn with HIV, either during pregnancy, during delivery, or through breastfeeding. Approximately two-thirds of perinatal infections occur during pregnancy or birth, and one-third occur through breastfeeding. UNAIDS estimates that approximately 600,000 infants are infected with HIV each year--90 percent of them in the developing world.
At the XIII International AIDS Conference, held July 9-14, 2000, in Durban, South Africa, numerous studies showed that short courses of either nevirapine or zidovudine (AZT) given to both mother and child reduced transmission of HIV from an infected mother to her child by up to 42 percent.
But in studies that followed these children for as long as two years, much of the protection--especially for those treated with AZT--appeared to vanish. Researchers then looked at the methods of nourishing the young children--particularly breastfeeding--and found that a substantial number of children who were free of HIV disease at birth later acquired HIV infection, most likely through breastfeeding. Many women breastfeed because they feel mandated to do so for cultural reasons or because they do not have access to uncontaminated water for formula.
While there was some discussion at the conference over whether long-term results justified a universal antiretroviral-based attack on MTCT, the moderator of one session that focused on MTCT, Kim Nichols (African Services Committee, Inc., New York), said, "These studies are so promising that we need to influence our governments to implement these programs."
Foremost among those studies was a comparison of a short course of nevirapine--one dose to the mother at the time of delivery and one dose to the child following birth--to a lengthier course of AZT [abstract LbOr1]. Research had already proved that AZT could reduce mother-to-child transmission by 30 percent or more. The HIVNET 012 trial, performed in Uganda, showed that nevirapine reduced transmission even more and that the results could be sustained for at least one year, with preliminary data indicating a continued benefit for several months longer.
"This is tremendous news," said Lynne Mofenson (Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Rockville, Md., USA), who co-moderated the session at which the study was presented.
"Through 18 months," said Thomas Fleming (University of Washington, Fred Hutchinson Cancer Research Center, Seattle), protocol statistician for HIVNET 012, "the reduction of HIV transmission from mother to infant--even in a breastfeeding population--is still significant. This regimen has the potential to reduce HIV mother-to-child transmission by 42 percent or more in places where other prevention regimens are impractical."
Maxi Owor (Mulago Hospital, Makerere University, Kampala, Uganda) presented one-year safety and efficacy data from the HIVNET 012 trial, a phase IIb trial that randomized 619 HIV-infected women and their infants to either nevirapine or AZT.
The two regimens:
The latest findings presented by Owor are a follow-up of breastfeeding mothers and their babies enrolled in a clinical trial conducted at Mulago Hospital and supported by the National Institute of Allergy and Infectious Diseases (NIAID, an agency of the US National Institutes of Health, Bethesda, Md.). Last year, results from that trial showed that a short regimen of nevirapine given to both mother and child significantly reduced HIV transmission. The information announced in Durban showed that the reduction in mother-to-infant transmission of HIV was sustained even though the infants were breastfed.
The new data Owor presented at the Durban meeting included 14- to 16-week transmission rates as well as transmission rates after one year of treatment.
In the study, the average age of the HIV-infected mothers was 25 years. The children were, as would be expected, nearly evenly split between boys and girls; 156 of the 308 children on AZT were female; 154 of the 311 children on nevirapine were female. The women were enrolled in the study between November 1997 and April 1999. All of them were in their ninth month of pregnancy and had not previously taken any antiretroviral drugs.
Owor reported that the children were administered tests for HIV RNA, using the Roche Amplicor testing kit at one to three days after birth; again six to eight weeks after birth; at 14 to 16 weeks; and at 12 months. They were also tested using ELISA and Western blot tests at 18 months.
The HIV transmission rates of 311 infants in the nevirapine cohort and 308 infants in the AZT arm of the trial showed similar rates of transmission at birth: 8.1 percent of the babies in the nevirapine arm were infected versus 10.3 percent of the infants receiving AZT. Owor said that at six to eight weeks, the HIV infection rate among the nevirapine babies was 11.8 percent compared with 20.0 percent for the children receiving AZT. At 14 to 16 weeks, the infection rate in the nevirapine group was 13.6 percent, compared with 22.1 percent among the AZT group.
When Owor examined the results after 12 months she found that 15.7 percent of the children receiving nevirapine had become infected with HIV, compared with 24.1 percent of the children on AZT. "That is [an] 8.3 percent absolute difference in infection and a 32 percent reduction in relative risk," she said. Preliminary data revealed that the difference continued through 18 months. The relative risk reduction reached 42 percent.
Among both the women and the infants, serious adverse events did not significantly differ between the nevirapine and AZT groups, Owor said.
"This study continues to indicate that a single dose of nevirapine given to HIV-positive women in labor and to the newborn within 72 hours of birth was safe and significantly reduced mother-to-child HIV transmission rate compared with [a] short course [AZT] regimen in this breastfeeding population," Owor said.
The study indicated, however, that some children who remain HIV-uninfected through childbirth still acquire the HIV virus later. "We still need to develop postnatal interventions to prevent infection," said Mofenson. Mofenson said that with universal implementation of the treatments for pregnant women around the world, "we can save the lives of 240,000 babies a year."
"These results are important because they demonstrate that nevirapine may be the most viable option studied to date for the developing world," said Brooks Jackson (Johns Hopkins School of Medicine, Baltimore), lead investigator of the HIVNET 012 study.
The drug can be stored at room temperature, an important consideration in resource-limited countries. Nevirapine tablets have been available since 1996, and a pediatric formulation was recently introduced, although the drug is not currently indicated for the prevention of perinatal HIV transmission.
In another study, researchers in South Africa found that nevirapine was equivalent to AZT plus lamivudine (3TC) in protecting children from acquiring HIV infection from their mothers.
Early results of the South African Intrapartum Nevirapine Trial (SAINT) found a transmission rate of 12.7 percent in mother-child pairs treated with nevirapine and a 9.5 percent infection rate in the mother-child pairs getting AZT/3TC, reported Daya Moodley (University of Natal, Durban) [abstract LbOr2].
Moodley said the trial scrutinized two short-course antiretroviral regimens previously shown to reduce rates of mother-to-child transmission of HIV within six weeks of birth. The two regimens were compared in a randomized open-label trial conducted at 13 sites in South Africa.
About 1,300 HIV-infected pregnant women were assigned to one of two treatment arms. In arm A, women received 200 mg of nevirapine during labor. One dose of nevirapine was administered to the mother and the infant 24 to 48 hours after delivery. In arm B, multiple doses of AZT and 3TC were administered during labor and then for one week after delivery to both the mother and infant.
The researchers used Roche Amplicor kits to determine the HIV status of the infants. Tests were performed within two days of delivery and at subsequent visits at four weeks, six weeks, and 12 weeks.
Moodley's group determined that there were 46 intrauterine infections among the 652 babies born to mothers receiving nevirapine--a 7.1 percent rate. This compared with 38 such infections among the 649 women who were receiving the AZT/3TC combination--5.9 percent. Peripartum infection rates were 5.6 percent for nevirapine and 3.6 percent for the combination arm. There were 9 (1.4 percent) perinatal deaths in the nevirapine arm and 17 (2.6 percent) perinatal deaths in the AZT/3TC arm. "However," Moodley said, "these differences were not statistically significant."
"Both of these regimens were effective," Moodley said, "with results comparable to those observed with nevirapine in HIVNET 012 and with [AZT/3TC] in PETRA [a perinatal transmission trial discussed later in this article]. Compared to current South African mother-to-child transmission rates, which are in excess of 20 percent, both the simple nevirapine regimen and the more involved and expensive [AZT/3TC] regimen demonstrated comparable efficacy in prevention of mother-to-child transmission of HIV-1 in the peripartum period."
Other researchers also confirmed AZT's effectiveness in preventing vertical transmission. The short-course AZT treatment, particularly favored in developing countries where extended medication is too costly, reduces the rate of mother-to-child transmission substantially, according to Stefan Wiktor (US Centers for Disease Control and Prevention [CDC], Atlanta) [abstract TuOrB354].
"There is a problem in keeping the children free of infection because often there is no acceptable alternative to breast milk for nutrition," noted Wiktor. Nonetheless, "Even in this breastfeeding population, the oral short-course [AZT] regimen significantly reduces overall mother-to-child HIV-1 transmission at 24 months of age."
Wiktor reported the pooled results of trials of AZT in pregnant women in the West African nations of Côte d'Ivoire and Burkino Faso. His research team's objective was to assess the 24-month efficacy of a short-course maternal AZT regimen for the prevention of mother-to-child HIV transmission in a breastfeeding population.
Working in cooperation with the National French AIDS Research Agency, Wiktor and colleagues treated the HIV-infected mothers of 641 children. Placebo pills were given to mothers of 322 children, while the other 319 mothers received AZT. HIV-infected women who were in their final weeks of pregnancy were recruited into the trials from September 1995 to February 1998. The women were randomized to receive either 300 mg of AZT or a placebo twice a day until labor, then oral therapy until delivery, then one tablet twice daily for seven days.
After six weeks, Wiktor said, 14 percent of the children whose mothers took AZT were infected with HIV, while 23.6 percent of the children whose mothers received placebo were infected.
Wiktor said that HIV infection in children was defined as a positive HIV-1 PCR, or, if the child was over 15 months of age, a positive HIV serologic test. Postnatal transmission was defined as a negative HIV-1 PCR through the first 30 days of life, followed by a positive HIV finding later on.
The researchers included 494 children in an analysis of postnatal transmission--233 from the placebo group and 261 from the AZT group. After two years, about 8 percent of the children whose mothers had received AZT had become infected, most likely through breast milk from their infected mothers. About the same percentage of placebo children were found to have acquired HIV postnatally.
Because transmission through breastfeeding does offset the reduction in transmission achieved by AZT therapy before and during birth, safe and acceptable alternatives to breastfeeding remain critical. Breastfeeding is a customary practice in West Africa with an average duration of nearly 14 months. In many places in sub-Saharan Africa, women who are unable to afford infant formula or who do not have access to clean water to prepare formula must breastfeed to prevent their children from starving.
"Breast-feeding transmits HIV, but remains a difficult practice to replace, particularly with the lack of viable alternatives," said Wiktor.
The World Health Organization has noted, "Among populations where breastfeeding is the norm, the risk that an HIV-positive woman will infect her infant ranges from 25 percent to 35 percent, of which about one-third is attributed to breastfeeding."
"The high risk of postnatal transmission, which was similar for the [AZT] and placebo groups, highlights the importance of identifying interventions to prevent transmission through breast milk," Wiktor said. "Additional interventions including therapy to reduce maternal HIV viral load need to be evaluated to prevent breast-milk transmission of HIV."
The average length of time that children in Wiktor's study were breastfed was 13.8 months, with 56.4 percent of children still breastfeeding at 12 months and 28.7 percent at 24 months. About the same numbers of children who were born to mothers on AZT or placebo were breastfeeding, Wiktor said. If a mother is HIV-infected, there is about a 10 percent risk of infecting the child through breast milk, Wiktor said. "That is apparently what occurred in this study."
In the UNAIDS-sponsored Perinatal Transmission (PETRA) trial, doctors evaluated three regimens of AZT/3TC, compared with placebo, among 1,754 women at five sites: two in South Africa, two in Uganda and one in Tanzania. There were 1,802 children born to the women enrolled in the randomized, double blind, placebo-controlled study.
The results of the PETRA trial were promising, showing that the antiretroviral agents, even in a short course of treatment, protected children from being infected during delivery. The six-week results:
About 30 percent of the women in the study delivered by cesarean section. About 70 percent of them were breastfeeding at six weeks.
When researchers at the Durban meeting reported the two-year outcomes, they were unable to find a statistically significant difference in mortality figures between those children in the placebo group and those in the active treatment arms [abstract LbOr5].
Glenda Gray (Perinatal HIV Clinic, Chris Hanney Hospital, Soweto, South Africa) said, "The follow-up data shows that women who are infected with HIV and breastfeed their children double the risk of infecting their child."
"The PETRA trial ... is unique among studies to prevent mother-to-child transmission of HIV because of its large sample size, multinational character, diversity of HIV subtypes, use of combination therapy, and inclusion of an intrapartum-only treatment arm," she said.
Gray reported that the six-week results showed a statistically significant difference in favor of the use of the antiretrovirals between arm A and placebo and between arm B and placebo. At that point, the reduction in mother-to-child-transmission was 52 percent in arm A; 34 percent in arm B. But when the mortality figures were assessed after 18 months, Gray reported that there were no longer any statistically significant differences in mortality among the four arms of the study.
In arm A, the children whose mothers had received antenatal, intrapartum, and postnatal antiretroviral treatment had a mortality rate of 20.7 percent; in arm B, the mortality rate was 24.4 percent; arm C, 25.7 percent, and arm D, the placebo group, 26.6 percent.
"As the study population is predominantly breastfeeding," Gray said, "the loss of efficacy of all regimens at 18 months of life is likely to result from a high number of HIV infections in breastfed children." Gray said the analysis of the timing of HIV infection in breastfed children is continuing. She said that analysis should "allow a better understanding of HIV transmission through breastfeeding, which will facilitate the development of feasible strategies to counter this."
UNAIDS issued a statement outlining policy implications from the latest results of the PETRA trial. "Antiretroviral intervention to reduce mother-to-child transmission should be pursued," the statement argued. "It is highly effective when women can avoid breastfeeding.
"Ways to improve the safety of feeding children born to HIV-infected mothers need to continue to be developed. The PETRA II trial in Uganda will examine whether antiretroviral therapy given to the newborn during the breastfeeding period protects against HIV transmission. Also in Uganda, a safe replacement feeding--homogenized and diluted cow milk supplemented with essential nutrients--is being developed for infants of HIV-infected mothers."
While acknowledging that it is not yet known exactly why the preventive effect of the antiretrovirals waned, UNAIDS still emphasized the danger of breastfeeding. The report said, "At 18 months, the treatment effect decreased. Whether this was due to differences in HIV transmission or to death from other causes is still unclear. However, the analyses show that breastfeeding was a highly significant determinant. Other predictors of unfavorable outcomes were low CD4+ cell counts and advanced clinical stage of HIV infection in the mother. Cesarean section appeared to confer a beneficial effect. These observations are in keeping with previous studies."
In an earlier report on the PETRA trial, the World Health Organization noted, "There is a continued risk of infection with HIV for as many months or years as breastfeeding continues, and, in the PETRA trial, most of the participants are breastfeeding."
The question of how the method of breastfeeding impacts transmission of HIV from mothers to children was examined in a prospective study undertaken by researchers at the University of Natal in Durban, South Africa [abstract LbOr6].
Anna Coutsoudis (University of Natal) said, "The risk of mother-to-child transmission of HIV through breastfeeding has not previously been examined in the light of the pattern of breastfeeding. We took a look at what type of breastfeeding is taking place among these mothers."
In particular, Coutsoudis said, the researchers differentiated between children who were exclusively breastfed and those who received both breast milk and formula (a practice referred to as "mixed breastfeeding"). After receiving counseling, mothers decided whether they wanted to breastfeed their infants or use formula. Some chose both methods, i.e. they chose mixed breastfeeding.
The women were recruited from July 1995 to April 1998 and were selected from a trial which was also investigating the role of vitamin A in the prevention of HIV transmission. A preliminary report of the South African Vitamin A Study Group had suggested that exclusive and mixed breastfeeding yield different rates of infection.
In 551 mother-baby pairs enrolled in the study, 157 of the babies were never breastfed, 118 were exclusively breastfed for three months, and 276 received mixed breastfeeding. The three feeding groups did not differ in any risk factors for mother-to-child transmission, and the probability of detecting HIV infection at birth was the same--7.6 percent among the formula-fed babies, and 6.9 percent in each of the breastfed cohorts.
Coutsoudis defined exclusive breastfeeding as the practice of giving a baby only its mother's milk for nutrition--no water, juices, formula, other liquids, or solid foods for at least three months after birth. A non-exclusively breastfed baby was given one or more of those sources of nourishment in addition to mother's milk.
Coutsoudis said that studies have suggested that exclusive breastfeeding might provide protection by creating a natural barrier against HIV in the child's digestive system. In contrast, the mixed feeding might create weaknesses in the gastrointestinal environment, allowing the HIV virus from the breast milk to be absorbed into the child's system and cause HIV infection.
After six months, the study showed, the percentage of HIV-infected babies who were never breastfed was 19.4 percent; similarly, 19.4 percent of the exclusively breastfed babies had acquired HIV. However, 26.1 percent of babies who received both breastfeeding and other sources of nutrition were HIV-infected after six months.
"These longer-term data support our early report that exclusive breastfeeding for three months lowers risk of mother-to-child transmission of HIV compared to mixed breastfeeding," Coutsoudis said. "Infants exclusively breastfed for at least three months and up to six months have no excess risk of HIV infection over those never breastfed. These findings, if confirmed elsewhere, can influence public health policies on feeding choices available to HIV-infected mothers in developing countries."
In particular, Coutsoudis said, "Exclusive breastfeeding may offer HIV-infected women in developing countries an affordable, culturally-acceptable, and effective means of reducing mother-to-child transmission of HIV while maintaining the overwhelming benefits of breastfeeding."
When the children were followed further, for as long as 15 months, the children who were exclusively breastfed still had a lower risk of becoming infected. About 25 percent of those children were infected, compared to 36 percent of children who had received mixed sources of nutrition.
In Thailand, researchers asked women to refrain from breastfeeding during a trial in which four different courses of treatment using AZT were explored [abstract LbOr3].
Perinatal HIV Prevention Trial (PHPT) investigators were trying to determine if a simplified and shortened AZT prophylaxis regimen could be as efficacious as Pediatric AIDS Clinical Trials Group protocol 076 (PACTG 076), which established that AZT could substantially reduce mother-to-child transmission of HIV. The researchers enrolled 1,398 women in one of four AZT regimens.
While the lengths of the regimens varied, they all featured the same dosages: for women, 300 mg of AZT twice a day until labor began, and then 300 mg of AZT every three hours; for newborns, 2mg/kg of AZT every six hours. The four regimens:
Although some of the regimens were difficult to follow, Sophie Le Coeur (Institut National d'Etudes Demographiques, Paris), who presented the paper in Durban, said, "All the treatments were well tolerated and there was a close adherence to feeding children with formula. These women were extremely compliant, showing their strong willingness to do what was necessary to save their children."
Le Coeur said the short-short course was abandoned early when preliminary results of the first safety interim analysis showed a marked increase in transmission compared with the long-long treatment. She said that in those early findings, the long-long regimen resulted in a 4.1 percent transmission rate while the short-short therapy resulted in a 10.5 percent transmission rate.
"The final figures confirmed the decision to discontinue the short-short regimen," she said. The long-long regimen resulted in a 6.7 percent transmission rate; the long-short treatment program resulted in a 5.7 percent rate and the short-long regimen resulted in an 8.4 percent rate.
The long-short and long-long regimens proved the study's hypothesis that a shorter period of treatment--which would save resources--was equivalent to the PACTG 076 trial, Le Coeur said. Equivalence between these regimens and the short-long protocol was borderline, she said.
(The landmark PACTG 076 was a randomized, double-blind, placebo-controlled US trial that revealed the effectiveness of AZT in preventing mother-to-child transmission of HIV. The treatment regimen consisted of 100 mg of AZT five times daily for the woman, beginning at 14 to 34 weeks of gestation [depending on when the woman was found to be HIV-infected and pregnant]; an intrapartum course of AZT administered to the woman intravenously; and 2 mg/kg of orally administered AZT for the infant every six hours for six weeks. Infants in the AZT group had an infection rate of 8.3 percent compared to an infection rate of 25.5 percent in the placebo group.)
PHPT, Le Coeur said, shows that both the long-short and the long-long regimens "appear safe, are easy to comply with, and are equally efficacious." These two regimens can both be implemented more easily and far more inexpensively than the original PACTG 076 regimen. While there may not be any added benefit to giving the six-week regimen to infants whose mothers have received the long treatment regimen, Le Coeur noted, the six-week regimen may prevent some infections among infants whose mothers have taken the AZT regimen for less time.
In areas of the world where women can receive high-quality prenatal care and where antiretroviral drugs can be afforded by individuals or by governments, some doctors talk about the possibility that mother-to-child transmission of HIV could be eradicated.
"New studies show us how far we have come toward eliminating mother-to-child HIV transmission in the United States, and how far we have yet to go in the developing world where such efforts are urgently needed," the CDC's Helene Gayle said.
Gayle cited studies which show that comprehensive prevention and treatment efforts in the United States have brought sharp drops in mother-to-child transmission of HIV [MoOrC239].
CDC epidemiologist Mary Lou Lindegren elaborated on this point by noting that perinatal transmission of HIV dropped by half between 1993 and 1997 in 32 US states that track perinatal HIV exposure and HIV infection. Lindegren reported that the incidence of perinatal HIV transmission fell from 20.7 percent in 1993 to 10.6 percent in 1997. (Researchers are still analyzing the 1998 data.)
"Declines occurred in all regions, in urban as well as rural areas, among racial and ethnic groups and especially among infants less than one year of age," Lindegren reported. The reduction among children under age one was 86 percent.
In these states, the study identified factors contributing to this success, including a sharp rise in the number of women who had learned of their HIV infection by being tested during pregnancy. In 1994 about 80 percent of these women were tested during pregnancy, but this figure rose to 96 percent in 1998. In 1994, about 30 percent of pregnant women used AZT to reduce the likelihood of transmission, but by 1998 nearly 70 percent of women were receiving the drug. In 1994, about 27 percent of infants were given AZT at birth, compared with 84 percent in 1998.
Using data from seven states with enhanced HIV surveillance (Colorado, Indiana, Louisiana, Michigan, Missouri, New Jersey, and South Carolina), Lindegren was able to identify factors contributing to transmission. "These data show significant progress, but they also highlight the importance of reaching all women, especially substance-abusing women, with early prenatal care, HIV testing, and access to preventive therapy," said Lindegren.
She said that about 35 percent of women giving birth to HIV-infected infants were using illicit drugs. In addition to preventive treatment, Lindegren said these women also need access to substance abuse treatment.
For women who seek care late in pregnancy, other interventions, such as rapid HIV testing during labor followed by initiation of therapy, will be important, Lindegren said. Increased education and outreach to physicians to encourage them to test all pregnant patients may also contribute to further reductions.
In scrutinizing the enhanced data collected from seven of the 32 states, researchers found that:
Her colleague Gayle suggested three possible strategies for further lowering the transmission rate in the United States:
While transmission of the virus to children in Western countries is becoming uncommon, only sporadic decreases are reported in the developing world, and philanthropic campaigns to provide medication to counter mother-to-child transmission do not always appear to be welcomed.
One possible reason--never spoken for attribution by doctors, officials or nongovernmental organization personnel--is that children who are born to HIV-infected mothers in resource-limited settings are extremely likely to become orphans. HIV-infected newborns rarely survive to age five, and most die within a year of birth, from a combination of HIV infection, poor health conditions, and the HIV-related illness or death of the mother.
Preventing the transmission of HIV to babies might only serve to increase the number of orphans in the developing world, which is expected to have 44 million orphans by the year 2010, according to the US Agency for International Development (USAID). In Africa, due to custom and culture, if a child loses one parent, the child is considered an orphan.
(Editor's note: While the International Association of Physicians in AIDS Care shares the view of most physicians that withholding preventive treatment in this situation is unethical, it is not clear whether or not all of the parties involved in establishing HIV/AIDS policies in resource-limited settings would agree.)
USAID officials said the vast number of children who have limited parental guidance will create severe social, economic, educational, and medical problems that will plague the continent for at least a third of the century.
Hardest hit will be the nations of Rwanda, Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Zambia, Zimbabwe and the Central African Republic--all of which will have more than 20 percent of their population under age 15 classified as orphans.
"AIDS is creating orphans at a rate unrivaled in world history," said Susan Hunter, co-author of the USAID-sponsored report, "Children on the Brink 2000." Hunter said that 80 percent of the orphans will lose parents due to AIDS.
Hunter said that already in five African countries, one-fifth to one-third of children under age 15 have lost at least one parent; by the year 2010, there will be six African nations in which 30 percent of the children under age 15 will be classified as orphans.
Some of the problems that need to be addressed relate to inheritance laws, researchers say. Sandy Thurman (White House Office of National AIDS Policy, Washington, D.C.) said that in some areas of Africa, when a man dies, his wife and children do not inherit, but his brothers will receive his land and possessions. That deprives a devastated family of not only the breadwinner but also a home, she said. The wife and family are then dependent on the brother for support, a situation that can lead to abuse.
She cited one Ugandan woman who was orphaned as a teenager and was subsequently raised in a relative's household, where she suffered sexual abuse. Now a 20-year-old college student, the woman has learned that she is HIV-infected. Thurman said that this is a typical scenario because these women and children are vulnerable and without resources.
"Girls are much more likely to become caregivers to their siblings and to ill parents, and girls often fall to the end of the line in educational opportunity," she said. "The gains women and girls have made in education are being wiped out by this epidemic."
Thurman said one possible solution is microfinancing cottage industries that support the caregivers of the orphans. "There is a grandmother in Uganda who lost 11 of 12 adult children to AIDS. She is caring for 35 grandchildren," Thurman said. Using loans from community institutions supported by US government funding, the woman was able to purchase pig and chicken breeding stock and has generated enough income to send 15 of the grandchildren to school and to get treatment for five other children who are HIV-infected.
Thurman said the woman has taken out and repaid five loans; the repayment rate of women in her neighborhood who have received similar loans exceeds 98 percent. "Citicorp should have such a good repayment rate," she wryly commented.
Thurman said the United States has earmarked $24 million for helping AIDS orphans. "It's more than any other country is donating for this purpose," she said. "But it's not enough."
She said that in Lusaka, the capital of Zambia, there are 100,000 orphans living on the streets. "I went out at night to look at the situation and I was surrounded by a sea of these children," she said. "It is an appalling situation. It was an unbelievable experience. They have developed their own little social networks with 10-year-olds taking care of younger children, not necessarily their own brother or sisters, and living in drainage ditches."
Yet, she said, the children fight to attend school so they can learn to read and write. The schools in Lusaka, she noted, can only care for 900 children a day, and can feed them just one meal a day.
John Williamson, a co-author of the USAID report, said that keys to solving the orphan crisis include mobilizing community-based services and providing economic and emotional support to help families cope with taking care of their relatives' survivors.
The costs of caring for millions of orphans, most of whom are not yet infected with HIV but are extremely vulnerable to contracting the disease; the costs of treating ill parents and ill children; the costs of supplying drugs to combat mother-to-child transmission--all hover like the sword of Damocles over Africa and other desperate regions of the world.
Ed Susman, a freelance medical writer who has been reporting on AIDS-related issues for 15 years, lives in West Palm Beach, Fla. (70317.410@compuserve.com).
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