Daily, 2000 children become infected through mother–child HIV transmission, including 200 in Asia [1,2]. In Thailand, mother–child HIV transmission already has infected 30 000 children, caused 7500 AIDS cases in children, and increased overall mortality rates among children 0–4 years of age in some areas [3–6]. The prevalence of HIV infection among the 900 000 women who become pregnant each year is 1–2% (Fig. 1), and approximately 13 000 children are born at risk for mother–child HIV transmission annually [4,5]. Without interventions, 4000 children would become infected each year, about one seventh of all new HIV infections . In 1998, Thailand became the first resource-limited country to implement a national program for preventing mother–child HIV transmission (PMCHT). This article recounts the development of Thailand's national PMCHT program, describes main components and early uptake of the program, and offers the lessons learned.
Thailand is administratively divided into provinces, districts, and subdistricts; in general, the Ministry of Public Health (MOPH) has a general hospital in each province, a community hospital in each district, and a health center in each subdistrict. In addition, the 75 provinces (excluding Bangkok) are grouped into 12 regions, each with at least one regional hospital. Nationwide, there are 92 general hospitals, 715 community hospitals, 9677 health centers, and 12 regional mother–child hospitals. All provide antenatal care and are linked by an established referral system. All hospital deliveries are supervised by a physician.
In addition to MOPH hospitals, where more than 70% of women give birth, other hospitals in Thailand provide antenatal care services, including private hospitals and government hospitals operated by the armed forces, the Ministry of University Affairs, and the Bangkok Metropolitan Administration.
MOPH policy calls for at least four antenatal care visits, the first of which should be within the first 6 months of pregnancy. Routine antenatal care services are medical history; physical examination; blood testing for anemia, blood group, hepatitis B antigen, syphilis, and HIV; urinalysis; diagnosis, treatment, and referral of women with high-risk pregnancies; tetanus toxoid vaccination; provision of vitamins and iron; and education on health, nutrition, and self-care. Except for laboratory testing, these services are free in MOPH hospitals; laboratory testing costs approximately 100–300 baht (US$2–7). Special funds are available for women who cannot afford this fee. Table 1 shows indicators related to maternal and child health in Thailand.
Development of program components
Antenatal HIV testing
In 1990–1991, several large hospitals began routine screening for HIV infection in antenatal clinics [8–10]. At that time, PMCHT interventions were not available and health care providers in Thailand had little experience with counseling for HIV testing . One early motivation for HIV testing of pregnant women was to identify which women were infected so increased precautions could be taken to reduce exposure of health care workers to HIV during deliveries . For pregnant women, the benefit of HIV testing was to learn their HIV status so they could decide about pregnancy continuation, subsequent birth control, and prevention of HIV transmission to partners. Although HIV infection is not a specific indication for pregnancy termination in Thailand, in some hospitals in the early 1990s, most pregnant women who learned they were infected with HIV before 24 weeks’ gestation terminated their pregnancies [13,14].
As PMCHT interventions became available throughout Thailand, additional hospitals began routine antenatal HIV testing. It was estimated that approximately half of pregnant women in MOPH hospitals were tested in 1995 and about 75% in 1997. Other surveys showed that in 1997, 83% of 480 physicians said they offered routine HIV testing to all obstetric patients , and in 1999, 97% of 749 hospitals reported routine antenatal HIV testing .
In current practice, voluntary HIV testing is routine for all women starting antenatal care; after receiving information about HIV and other routine antenatal tests, women are encouraged to consent to confidential HIV testing. The HIV testing algorithm uses an enzyme-linked immunosorbant assay (ELISA) for initial screening . Positive results are confirmed with a second ELISA test from a different company or a rapid test. Gel particle agglutination or Western blot tests are used to resolve discordant test results. Results are usually available within 1 week. HIV testing is available at all community, general, and regional hospitals but not at most health centers, where antenatal care in rural areas is often initiated. For women starting antenatal care at health centers, referral systems are in place for blood testing at nearby hospitals. Many hospitals also routinely offer repeat blood testing in the third trimester .
Women who did not have consistent antenatal care may come to the hospital in labor without having had a test . Many hospitals now routinely offer a rapid HIV test to women in labor who were not tested during pregnancy. Brief information is given and consent is obtained before testing. Postpartum, women with positive test results are provided posttest counseling and other PMCHT interventions.
Beginning in 1991, more than 600 nurses were trained in basic counseling skills to work in anonymous HIV counseling and testing sites set up by the MOPH throughout Thailand. In response to the increase in HIV infections among pregnant women in 1991–1992 and the increase in antenatal HIV testing, the MOPH sought to ensure that antenatal testing was voluntary and always accompanied by pretest and posttest counseling, and that test results were confidential and made known to the patient. In 1993, a 5 day training curriculum for antenatal HIV counseling was developed; by 1994, voluntary and confidential HIV testing accompanied by pretest and posttest counseling was implemented as part of routine antenatal services in many hospitals in Thailand [9,17]. With the benefit of counseling experience gained from conducting clinical trials of short-course zidovudine in Thailand, the antenatal counseling curriculum was updated in 1998 to support pilot projects implementing short-course zidovudine [19,20].
In current practice, HIV pretest counseling is usually done at the first antenatal visit and may be conducted individually or in a group, sometimes aided by the use of a videotape . Posttest counseling of HIV-seropositive pregnant women is always done individually and addresses disclosure of HIV status to partners, taking zidovudine, infant feeding, and future child care planning [19,20]. Whereas pretest counseling and posttest counseling of HIV-seronegative women can be done at health centers, posttest counseling of HIV-seropositive women is generally done in hospitals where experienced counseling staff are available. Most counselors are nurses or social workers trained in maternal and child health HIV counseling who do not work exclusively as counselors but also perform other maternal and child health duties.
In 1994, results of the AIDS Clinical Trials Group (ACTG) protocol 076 were announced. This trial demonstrated that a zidovudine regimen given for approximately 3 months during pregnancy, administered intravenously during labor, and given for 6 weeks to newborn infants could reduce mother–child HIV transmission by two thirds in the absence of breastfeeding . This regimen was rapidly adopted as standard practice in countries that had health care systems and financing to support it . In June 1994, World Health Organization (WHO) consensus workshop participants concluded that, because the regimen's cost and complexity limited its general applicability, no recommendations regarding its use could be made for resource-poor countries.
In 1995, the World Bank, the WHO, and the MOPH reviewed antiretroviral drug use in Thailand. This review determined that, although the government of Thailand was supporting the costs of zidovudine monotherapy for treating low-income adults with AIDS, only approximately 5% of the total number of persons living with AIDS in Thailand had received zidovudine . This review further concluded that using zidovudine for PMCHT would be more cost-effective than using it for treating persons with AIDS. However, given the high per capita cost of the regimen of zidovudine used in the ACTG 076 trial and the large number of women needing such an intervention in Thailand, the MOPH did not support the routine use of this regimen and most physicians did not use it . Instead, the MOPH collaborated in partnerships to conduct two phase III clinical trials to study shorter courses of zidovudine and began planning operational research to implement PMCHT programs using short-course zidovudine.
In the first trial, the MOPH collaborated with Mahidol University and the US Centers for Disease Control and Prevention (CDC) to study the efficacy of short-course zidovudine in Bangkok; results showing that short-course zidovudine reduced transmission by 50% compared with placebo (9.4% versus 18.9%) were available in early 1998 [24,25]. In the second trial (Perinatal HIV Prevention Trial), the MOPH collaborated with Chiang Mai, Mahidol, and Harvard Universities, and the French Institut de Recherche pour le Dévelopement in a trial to determine if a similar short course of zidovudine was as efficacious as a longer course; results showing the shorter course inferior to the longer course (10.5% versus 4.1%) were available in 2000 .
Although the MOPH did not support or recommend the routine use of the ACTG 076 regimen of zidovudine in Thailand, some physicians wanted to use it for their patients. To help meet this demand, the Thai Red Cross, a non-governmental organization, began a public donation campaign in 1996 [27,28]. In this program, physicians taking care of low-income HIV-infected pregnant women can request on a case-by-case basis that their patients be included. If the request is approved, the program provides the physician with zidovudine for a regimen similar to the ACTG 076 regimen, though with oral dosing during labor. Through 1999, 2891 women were served in this program in 81 hospitals in 40 provinces; of 726 children tested, 6.0% were infected with HIV.
In 1997, the MOPH decided to conduct operational research using short-course zidovudine as part of a comprehensive program for PMCHT in MOPH hospitals. The first of these projects began in 1997 in Region 10, which comprises six provinces in northern Thailand where approximately 40 000 women give birth each year, 4% of whom are infected with HIV. The project was conducted in coordination with the Perinatal HIV Prevention Trial and used a short-course zidovudine regimen similar to the one studied in that trial . Through December 1999, 82% of 76 750 women in antenatal care were tested for HIV, and 86% of 2341 HIV-infected women were provided with zidovudine. Of 390 children tested, 7.7% were infected with HIV .
A second pilot project began in July 1998 in the seven provinces of Region 7 in northeastern Thailand, where approximately 80 000 women give birth each year, 1% of whom are infected with HIV . The zidovudine regimen used was that found to be effective in the Bangkok trial and subsequently recommended by the WHO [25,32]. During this 2 year project, 70% of 153 598 women who gave birth were tested for HIV, and 69% of 918 HIV-infected women received zidovudine. The most common reasons for not receiving zidovudine were not knowing about zidovudine and premature delivery. Of 293 children tested, 9.6% were infected with HIV [33, 34].
In current practice, zidovudine for PMCHT (Fig. 2) is purchased at the national level. Generic zidovudine tablets are purchased from the Government Pharmaceutical Organization, a state enterprise in Thailand. Zidovudine syrup is not yet made in generic form and must be purchased from a commercial pharmaceutical company. The national budget for zidovudine is divided each year by region, based on the number of HIV-infected women in antenatal care estimated from HIV serosurveillance data. Each region distributes zidovudine to its provinces, which further allocate it to hospitals based on usage reports. Physicians prescribe zidovudine to women and infants; counselors explain the use of zidovudine and assess the amount used by interviewing the women and counting unused pills.
In 1992, the WHO issued guidelines on infant feeding and mother–child HIV transmission . Considering the low risk of infant death from other infectious diseases and malnutrition in Thailand, the MOPH in 1993 recommended that all HIV-infected women be discouraged from breastfeeding. In the same year, the MOPH also allocated funds to purchase infant formula for women on low incomes. The budget was first set at a level to provide a 2 year supply of free formula for the estimated 10% of HIV-infected women who were thought to be below the poverty line. However, concerned that formula supplies for poor HIV-infected women would be inadequate, and noting the increasing number of pregnant women in whom HIV infection was diagnosed, the MOPH argued successfully to increase the budget allocation for formula in 1997. Since other acceptable feeding options are available for older children, the period of formula support was reduced to 1 year per child, allowing more children to receive formula. In 1999, the budget for formula was increased substantially to support the national PMCHT program and now is large enough to buy formula for nearly 10 000 HIV-infected women annually.
In current practice, infant formula is distributed to the regional health promotion centers and in turn to the provinces and hospitals in a manner similar to that for zidovudine. At the hospital level, counselors generally distribute formula to HIV-infected women monthly. In recent evaluations of the PMCHT program, 4–6% of HIV-infected and 86–95% of HIV-uninfected women breastfed their babies, suggesting little change in infant feeding choices among uninfected women [34,36]. However, concerns about revealing their HIV status by formula feeding were reported by 31% of the infected women .
National implementation of PMCHT program
Beginning in 1998, the results of successful research and pilot implementation projects led physicians in most provinces to demand government support for short-course zidovudine. The MOPH began supporting nationwide integration of a PMCHT program into its existing maternal–child health program. In 1999, the MOPH convened an expert panel to review existing data and help to determine national policy for zidovudine and other interventions for PMCHT (Fig. 2) .
By 1999, zidovudine was being used in most hospitals in Thailand. In a survey of 749 hospitals with maternity services in February 1999, 96% reported offering HIV testing, 69% reported offering antenatal zidovudine, and 29% reported offering newborn zidovudine . Where used, antenatal zidovudine was started at ≥ 36 weeks’ gestation in 70% of hospitals. These findings contrast with those of a May 1997 survey in which only 20% of physicians providing obstetric care reported using zidovudine for PMCHT .
With support from CDC, the MOPH began a national system to monitor its PMCHT program in 2000. This computerized system collects summaries of 44 data items from each hospital monthly to monitor key indicators of antenatal care, HIV testing, and use of zidovudine and formula. Based on reports received from 669 hospitals in 65 provinces for the period October 2000 through July 2001, 93% of 318 721 women who gave birth had been tested for HIV, 69% of 3958 HIV-seropositive women giving birth had received zidovudine, and 86% and 80% of the 3865 children born to HIV-seropositive women had received zidovudine and infant formula, respectively, through the program (Table 2).
Lessons learned and future challenges
Some aspects of Thailand's health care infrastructure (e.g., antenatal care system, clean water) and HIV epidemic (e.g., relatively low HIV prevalence) that have contributed to its ability to mount its national program may not be present in other countries. For instance, it may be more feasible for countries with lower uptake of antenatal care to rely on intrapartum nevirapine rather than antenatal zidovudine for PMCHT.
Despite these differences, several lessons learned from Thailand's experience may be useful for other countries considering implementing national programs:
* Pilot PMCHT projects provide a setting to work out feasible referral and management protocols and solve problems; if successful, they provide data to advocate for expansion.
* Frequent communication throughout PMCHT programs is needed to establish good teamwork, clarify responsibilities and work flow, disseminate policy, and solicit and heed input from staff at all levels.
* Training, especially in counseling, is critical for preparing counselors and their supervisors. Periodic re-training is needed because of staff turnover and rapidly evolving technical issues.
* Counseling plays a central role in PMCHT programs by informing pregnant women about HIV testing and prevention, and helping HIV-infected women to adjust to their diagnosis and reduce transmission to their children. Skill in counseling can enhance the quality of antenatal and other health services in addition to PMCHT.
* Data from surveillance, research, monitoring, and evaluation provide evidence to advocate for developing, expanding, and improving PMCHT programs. Simple data systems that allow accurate information to be easily collected, quickly analyzed, readily understood, and rapidly disseminated enhance their usefulness.
* Integrating PMCHT into maternal and child health services simplifies program management at the hospital level. For instance, messages about breastfeeding, which differ for HIV-infected and HIV-uninfected women, are easier to deliver consistently when the same counselors are trained in the reasons for promoting breastfeeding for HIV-uninfected women and discouraging it for HIV-infected women.
* Non-governmental organizations and research groups can catalyze programs by providing services before the government is able to do so, and can gain early PMCHT program experience useful for policy making.
Based on pilot project data, we estimate that implementation of Thailand's PMCHT program could reduce the average risk for mother–child HIV transmission from 30% to less than 10%, preventing 2500 infant infections each year. To achieve and maintain this prevention effect, national monitoring and evaluation data should be reviewed frequently to identify areas where the program can be improved. In addition, clinical, counseling, and management training related to PMCHT should be provided regularly at the national level to update health care personnel on new information and technologies, to train new staff, and to avoid staff ‘‘burnout.’’ Finally, political and budgetary support should be maintained, while adapting to the changing economy, health care reform, and government decentralization in Thailand. To improve the PMCHT program, the MOPH has begun to research more effective interventions, improve the care of HIV-infected women and their children, meet the needs of the growing number of HIV-related orphans, and enhance efforts in the antenatal and postpartum settings to prevent heterosexual transmission.
We thank Ms Nareeluck Kullert of the Ministry of Public Health and Dr Achara Teeraratkul and Ms Monsicha Poolsawat of the HIV/AIDS Collaboration for providing helpful information.
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