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310th Meeting – Tuesday, March 17th 2009

"HIV Research and Public Health in Thailand: Prevention and Care"

A talk by Marc Lallemant - Director of Programs for HIV Prevention and Treatment (PHPT) and his colleague Dr. Gonzague Jourdain

Present: Linda Rochester, Christa Sollner, Mark Tuckson, Rebecca Weldon, Sithiwong, Mark and Dianne Barber-Riley, Nance Cunningham, Oliver Hargreave, Louis Gabaude, Klaus and Heidi Berkmuller, Kongkaew Inthanon. An audience of 12 plus a few more.

A brief summary of Marc's and Gonzague's presentation

This summary is adapted from a paper published in "AIDS in ASIA" (Max Essex: Editor), Kluwer Boston; 1st ed. (Jul. 14, 2004) with information available on www.phpt.org

Of all Asian countries, Thailand was one of the first and hardest hit by the first Human Immunodeficiency Virus (HIV-1) pandemic. A national surveillance system was implemented in 1989 to monitor the spread of the epidemic to the general population: in 1994, the prevalence of HIV infection in pregnant women presenting at the antenatal clinics exceeded 10% in highly impacted regions such as Phayao, which is located in the Northern part of the country. With the nationwide prevention campaigns, the prevalence rates in pregnant women dropped significantly. In June 2006, the prevalence rate of HIV-1 among pregnant women was less than 1% nationwide, with the highest rates found in the Central and Eastern provinces of the country. Despite this outstanding progress, many infants in Thailand are still born to an HIV infected mother and are at risk of acquiring the Human Immunodeficiency Virus (HIV) causing the Acquired Immune Deficiency Syndrome (AIDS). Thailand currently has an estimated 570,000 people living with HIV.

Thai response to the epidemic The Royal Thai Government responded quickly to the HIV/AIDS epidemic and implemented a multi-sector AIDS program. At its onset, this program involved all government ministries, non-governmental organizations, multilateral donors and private businesses. Cooperation at the national level among ministries was carried out through the National AIDS Prevention and Control Committee chaired by the Prime Minister.


1. Public information, education and prevention

As early as 1989, bi-annual sentinel surveillance surveys were conducted in each province among drug users, direct and indirect commercial sex workers, military recruits, blood donors, and antenatal care women. The data collected highlighted the most affected provinces and documented the dynamic of the epidemic spreading from one group of high- risk behaviors such as sex workers to other sectors of the general population such as the military recruits. The publication of these prevalence results in the national newspapers, illustrating the visible progression of the epidemic, was instrumental in raising public/government awareness towards the spread of the HIV/AIDS.

The government responded with several national campaigns, bombarding the public with information on HIV/AIDS using all forms of mass media as well as innovative and powerful methods of communication. For example, a nationwide network of volunteers was mobilized to distribute cards, audio-cassettes and videos containing information about AIDS. Condom use was heavily promoted through the 100% condom use campaign in which the active involvement of the charismatic public figure, Mechai Viravaidya was critical for its success. Finally, HIV testing was rapidly made available in all government hospitals and in many private facilities. The comprehensive monitoring and surveillance system in place since 1989 enabled the documentation of the success of these prevention programs in curtailing the spread of the epidemic. Indeed, the impact of these preventive measures was particularly visible in the North. For example, the prevalence rates in pregnant women dropped from more than 10% to less than 5% between 1994 and 1997 in the Phayao province, to around 2% today. The surveillance system also allowed observers to follow the epidemic, demonstrating the overall HIV prevalence decline in commercial sex workers and in the general population, while pointing out the relative failure of the campaign among intravenous drug users

2. Human rights and social support

A national counseling plan was launched in 1990 including training of counselors, and promotion of voluntary anonymous HIV counseling and testing at the national level. This plan was expanded in 1993 to provide training for nurses in the antenatal care setting. In addition, the government took a clear stand against the discrimination of HIV-infected individuals and the protection of their rights. For example, calls for mandatory blood testing and result disclosure were strongly opposed to.

The government also supported many Non Governmental Organizations (NGOs) involved in various aspects of HIV/AIDS prevention and care including home care, building AIDS patients network, income generating activities, family support groups, etc. For example, the Thai Business Initiative in Rural Development, a project aimed at diverting young rural women from prostitution by providing them with training and employment.

3. Promotion of research

Important epidemiological, clinical, virological and socio-behavioral research programs conducted in Thailand were encouraged and supported by the Ministry of Public Health. The research allowed a better understanding of the dynamic of the epidemic and documented uniquely in the world the success of the prevention campaigns (Nelson et al, 1996). These research programs also helped instigate pilot projects, which were launched at the regional level, and proved to be crucial in guiding interventions and policies at the national level. The close collaboration between researchers and policy makers at the Ministry of Public Health was particularly effective in the field of mother-to-child prevention. Finally, Thailand was and continues to be actively involved at the forefront of the global research effort towards an HIV/AIDS vaccine, coordinated by a National HIV vaccine committee of knowledgeable experts.

4. Medical treatment and care

The use of zidovudine (AZT), the first antiretroviral with proven clinical efficacy, was approved in 1987, and until the mid nineties it was provided by the Ministry of Public Health to HIV-infected patients. The Thai Food and Drug Administration (FDA) then rapidly allowed the importation of many other antiretrovirals. Later, an agreement between the Thai government and the manufacturer of AZT allowed the Government Pharmaceutical Organization (GPO) to purchase the drug in bulk at a competitive price. In 2002, the GPO started producing several generic antiretroviral fixed dose combinations (ARV) including GPOvirS and GPOvirZ pills to be taken twice a day opening access to triple therapy at affordable price (1,200 Baht per month in 2004). With the expansion of access to treatments through the national program, in 2009 over 197,000 persons receive antiretroviral treatments under the universal coverage system. Approximately 50,000 receive treatment from other programs.

A success story : Prevention of mother-to-child transmission program Within the national HIV/AIDS prevention program, Thailand specifically targeted mother-to-child transmission of HIV.

From as early as 1990, even before any measures to reduce mother-to-child transmission of HIV were discovered, some hospitals were conducting HIV testing for pregnant women. At that time, this practice reflected general fears among health care workers who felt the need to know the HIV status of their patients in order to protect themselves. However, when discovered to be HIV-positive, most women were informed of their HIV status.

Theoretically, the women could then make a decision with regard to the continuation of their pregnancy; decide about infant feeding mode, post-partum contraception and prevention of sexual transmission to their partners. At this time, most women confirmed as HIV positive had their pregnancy terminated, while many of those who continued with their pregnancy were sterilized thereafter. This trend reflected the fact that most health care workers felt they had nothing to offer these women who were often perceived as unable to manage a pregnancy and raise a child. This attitude amongst the health care workers changed significantly, from 1993, when the intense training on HIV counseling provided by the Ministry of Public Health was extended to nurses within the antenatal care settings.

In the same year, in response to the clear evidence that HIV could be transmitted through breastfeeding, the Ministry of Public Health recommended formula feeding to HIV-infected women only, while continuing to support the UNICEF Baby-Friendly Initiative and promoting breastfeeding in the general population. In the public hospitals, formula milk was provided for free to the poorest of HIV-infected women until the child reached 18 months of age. The Ministry of Public Health ensured that this recommendation was only targeted towards HIV-infected women who could then decide on the safest mode of feeding for their infants.

As soon as the results of a clinical trial in the United States and France were released in 1994, demonstrating the remarkable efficacy of zidovudine (AZT) in reducing perinatal transmission of HIV, the Ministry of Public Health reevaluated its HIV treatment program and concluded that, given Thailand's budget for antiretrovirals and the quality of its health care infrastructure, AZT prophylaxis for HIV-infected pregnant women and their newborns was feasible, affordable and by far the most cost-effective way to use the budget for antiretrovirals compared to the use of AZT mono-therapy for patients. At about this time, the Thai Food and Drug Administration approved the use of AZT for the prevention of perinatal HIV.

By 1996-1997, after completing preliminary research studies, the Thai Red Cross began providing AZT to HIV-infected pregnant women in its affiliated hospitals throughout the country using funds raised with the help of members of the royal family. Knowing that most mother-to-child transmission occurs close to delivery, the Ministry of Public Health quickly initiated in northern Thailand a pilot perinatal HIV prevention program using a short course AZT treatment. This program was established in collaboration with a large clinical trial, the Perinatal HIV Prevention Trial (PHPT-1, see www.phpt.org) conducted by Harvard University and the French Institut de Recherche pour le Dveloppement (IRD). The main objective of this trial was to compare the efficacy of abbreviated AZT treatments in mothers and/or children with the regimen tested in the US and France. PHPT-1 demonstrated that a short course of AZT prophylaxis (delayed until 35 weeks gestation, and for 3 days in the newborn) was less effective than a long one (from 28 weeks gestation and 6 weeks in the newborn) with transmission rates of 10.5% versus 4.1%, respectively. Both programs, the Ministry of Public Health program in the North and the PHPT-1 research study complemented each other greatly and both benefited from the other's program in terms of training, coverage, and capacity building.

In December 1999, the Ministry of Public Health convened a meeting to issue national guidelines on perinatal HIV transmission prevention, based on evidence from clinical trials, along with the pilot programs and the Ministry of Public Health decided to launch its first nationwide perinatal transmission prevention program.

These great achievements were made possible due to a variety of factors:  the pragmatic approach of the Ministry of Public Health using the latest scientific knowledge from clinical research, testing them through pilot projects before scaling up to the national level; emphasizing on training particularly on HIV counseling, the high quality of HIV testing and health care system delivery.

The most striking results of the Prevention of Mother to Child Transmission of HIV (PMTCT) program is uniquely illustrated by the dramatic drop in number of pediatric AIDS cases reported to the Ministry of Public Health, although this also reflects the impact of the public campaigns on the prevention of sexual transmission.

Following the results of another trial in Uganda demonstrating the efficacy of one dose of nevirapine (NVP) at onset of labor and 2 days after birth in the newborns, the Perinatal HIV Prevention Trial 2 (PHPT-2; see www.phpt.org) tested the addition of one single oral 200 mg dose of nevirapine at onset of labor and one 6 mg dose for the newborn 48 to 72 hours after birth to the standard AZT regimen. The transmission rate in women who received zidovudine (AZT) plus nevirapine (NVP) was 2.0%, significantly lower than the 6.3% transmission rate experienced by women who received AZT alone. This simple regimen of AZT during the last trimester of pregnancy combined with a single dose of NVP at onset of labor is able to achieve transmission rate as low as those obtained using a triple combination regimen, or Highly Active Antiretroviral Therapy (HAART) during pregnancy. Following the remarkable results of this trial, the Ministry of Public Health has again responded in a pragmatic manner, convening a meeting of experts and reviewing its national guidelines for the prevention of mother-to-child transmission of HIV in order to advance the initiation of AZT from 28 weeks gestation and incorporate nevirapine (NVP) in the prevention package. Also, the World Health Organization (WHO) decided to recommend this treatment for pregnant women who do not need immediate combination therapy for their own health.

Moving towards Access to Highly Active Antiretroviral Therapy (HAART) The extension of the Prevention of Mother to Child Transmission of HIV (PMTCT) program to include long term provision of Highly Active Antiretroviral Therapy (HAART) to immuno-compromised mothers and to the few infected children is referred to as "PMTCT Plus". For example, immuno-compromised HIV-infected mothers and infected children who had participated in the Perinatal HIV Prevention trials have received antiretroviral fixed dose combinations (ARV) drugs since 1999 and continue to be closely monitored. The follow-up of these cohorts has demonstrated that "PMTCT Plus" was feasible, well accepted and highly beneficial to the patients involved. "PMTCT Plus" was also identified as a unique opportunity to reach out and treat HIV-infected fathers/partners so that both parents can care for their children.

In May 2001, during the Third International Symposium on Pediatric AIDS in Thailand, in a public Declaration, the clinicians, researchers and public health officers requested from the Ministry of Health the provision of Highly Active Antiretroviral Therapy (HAART) to infected mothers, children and families within the Thai national Prevention of Mother to Child Transmission of HIV (PMTCT) program.

With the increasing production of generic drugs worldwide, the price of antiretroviral fixed dose combinations (ARV) drugs has dropped dramatically, and the possibility of providing long term ARV treatment to HIV-infected patients has become more realistic. In Thailand, the Government Pharmaceutical Organization (GPO) started producing GPOvir, a combination of d4T, 3TC and nevirapine in a single pill to be administered twice a day, which costs approximately US$30 a month.

Using the same strategy of building upon the success of small pilot programs before scaling up nationally and using the results of the clinical trials performed in Thailand, the Ministry of Public Health organized in 2003 the revision of the national guidelines for the use of antiretroviral fixed dose combinations (ARV) and launched, in collaboration with the Global Fund, a national program to provide access to Highly Active Antiretroviral Therapy (HAART) to 70,000 patients over the next five years.

In clinical trials, antiretroviral therapy has been shown to have a dramatic impact on reducing the risk of progression to AIDS and death in HIV-infected adults and children. Large observational cohorts in Europe and the US demonstrated the impact of antiretroviral therapy on mortality in HIV-infected patients in routine care settings, with up to 70% reductions in risk of death.

With support from the Thai Ministry of Public Health, Oxfam GB and the Global Fund, PHPT/IRD program has been working within 50 public hospitals throughout Thailand to provide treatment for the participants of the research studies and other people living with HIV/AIDS. All patients in this treatment cohort are monitored to ensure their safety and to examine the efficacy and impact of the treatment provided.

In 2002, Perinatal HIV Prevention Trial (PHPT) submitted a joint proposal to the Global Fund to fight AIDS, TB and Malaria (GFATM) to demonstrate the feasibility of the provision of high quality HIV care including antiretroviral treatment. The PHPT-GFATM program will have provided antiretroviral fixed dose combinations (ARV) treatment and monitoring to more than 2,000 patients, one third of whom are children.

To ensure optimal use of antiretrovirals and the durability of drug regimens, the program highlights the critical importance of active involvement of People Living with HIV/AIDS, the need for hands-on training of medical professionals and the benefits of establishing independent networks of HIV care specialists. The development of clear procedures for patient screening, clinical and biological evaluations and systematic data collection enabled the program to document the high rate of virological and immunological success and low rate of mortality achieved.

This cohort is closely monitored with regular clinical and demographic data collection. To inform future policies and programs in order to optimize benefits of antiretroviral therapy, data are analysed to address the following key research areas:

… Long term efficacy of antiretroviral therapy: long term survival, factors associated with survival, immunological and virologic response
… Antiretroviral safety: incidence and risk factors to toxicities,
incidence of hospitalisation/serious adverse events (HIV related, ARV related, others)
… Drug resistance: durability of first line regimen and patterns of resistance, resistance mutations at baseline.
… Co-infections: HIV and Hepatitis B, Hepatitis C and tuberculosis
… Adherence to therapy
… Cost effectiveness of antiretroviral treatment: diagnosis strategies for infants born to HIV infected mothers, treatment regimens, monitoring strategies.

Through ongoing training and the development of specific clinical procedures, the program will continue to strengthen HIV care teams and their collaboration with people living with HIV/AIDS.

For more information, please visit the www.phpt.org website.

The presentation concluded with a question and answer in which members of the audience asked the speakers for more information on many of the topics outlined in their talk.

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