PROGRAMME 6 ANGLAIS.HTM

Strategies that can be used in Africa to reduce the transmission of the Human Immuno-deficiency Virus (HIV) from mother to child : a study of practicability, tolerance and acceptability of two medicinal interventions centered on the perinatal period, AZT tablets and vaginal capsules containing chlorine of bensalkonium (N. MEDA et al).

1.1. Abridged title: the decrease in the transmission of HIV from mother to child

1.2. Discipline : medicine, epidemiology

1.3. Calendar
- beginning : January 1995
- end : December 1997

1.4. Attachment :
Département : Conditions de Vie et Développement,
Unité de recherche : Santé,
Programme SIDA

1.5. Partners
- Ministry of Health, Burkina Faso and Côte d'Ivoire
- Muraz Center / OCCGE, Bobo Dioulasso Burkina Faso
- CEDRES Abidjan Côte d'Ivoire
- Unit of INSERM 330, University of Bordeaux II, Bordeaux, France
- Teaching Hospital, Cochin - Port Royal, Paris, France
- Sponsor - National Research Agency on AIDS, ANRS, France.

2. Presentation
2.1. Research Problem
This research covers the infection of the child by the HIV, the mother being the originator. This, comparable to that of sexually active adults, has become a world-wide epidemic, especially in Africa. The research consists in testing, two potentially interesting interventions within the strategies of the reduction of the transmission of HIV from mother to child (TMC) in developing countries. These two interventions are centered on the last month of pregnancy, during delivery and the immediate post-partum. In fact numerous arguments in the fields of immunology, serology and virology turn to prove today that the HIV TMC would occur during the final weeks of pregnancy, delivery and breastfeeding. Two factors seem to be predominant during the TMC of the HIV: firstly a high level of maternal blood viral charge and secondly the presence of the HIV in the cervico-vaginal secretions. The child would get infected when he comes into contact with it. Also our hypothesis is to test to see if a reduction in the blood viral within the mother and or the disinfection of the genital area with an antiseptic could reduc the risk of the TMC of the HIV. The antiretroviral drug used is zidovudine (AZT). It is chosen for it has been shown in Europe and in the United States that it possesses a remarkably effectiveness in reducing the TMC of the HIV. Unfortunately, the strategy of application of this treatment as experimented in France and in the U.S has proven to be difficult not to say impossible to be realised exactly in developing countries considering the obstetrical services in place and the total cost of such an operation. Thus an alternative using a simplified and short administration of AZT centered on the last month of pregnancy, during delivery and the precarious post-partum has been proposed and this is what is being tested now.
Regarding the genital parts, the chosen drug is Benzalkonium chlorine CdB in the form of genital capsules. In Africa, nothing is known about the clinical and biological tolerance, the acceptability of the product we plan to test. Concerning especially AZT which contains a certains amount of haematologic toxicity, it is crucial to be assured that this risk is not high as the rate of maternal aneamia is very high. With the desinfection of the vaginal area, the repeated use of local antiseptics other than CdB has already shown elsewhere that there are some risks of genital ulcerations. This effect nullifies the advantages of these medical products in the prevention of the sexual transmission of the HIV. Moreover, these two measures, especially the application of AZT, requires a prenatal tracking down of the HIV infection for there is a great fear in accepting to use them by the community. Again these measures demand an assiduous observance of the treatment and a reinforced prenatal supervision different from the habitual practice. Thus these measures are difficult to put in application in a routine way in Africa because of other obstretical interventions such as martial supplementation and the chemical prevention of malaria. On the whole, the worldwide practicability and the acceptability of these measures cannot be right away considered as a final result. Thus before planning to make a study of the effectiveness of these two measures on the TmC of the HIV, our main preoccupation consists in verifying among pregnant women in Africa the clinical and biological tolerance and the socio-cultural acceptance of these potential measures of prevention.

2.2. Objectives
- Study the clinical and biological tolerance of the AZT tablets with a 250 g dose and CdB vaginal capsules among pregnant women and their children in West Africa.
- Evaluate at the same time the acceptability of the testing of the HIV infection by pregnant women, the observance of a daily treatment covering from four to six weeks and an intensive assiduous prenatal supervision.

2.3. Methods
The research has planned and established in two centers of maternal and child health (SMI) in Burkina Faso and two others in Côte d'Ivoire, couselling and voluntary and confidential testing units concerning the HIV. It sorely concerns pregnant women infected by the HIV-1 or HIV1 and 2 and who have no haematological counter indications (severe anaemia, silkle cell, severe neutropenia, hypertransaminasemie). The study comprises two clinical trial tests of stage IIb chosen at double blind random comparing AZT and CdB capsules in placebo. In both trial tests the number of subjects to be examined was fixed at 150 for AZT denominate "trial ANRS 049a" and CdB "trial O49b". Each therapeutic section and placebo section will comprise 75 subjects. The supervision will be precarious from the inclusion to 145 post partum and later. The target date is fixed for the 15th month of the life of the child.

Additional research is possible with such a plan and it has been planned. Thus the fact that this study will make it possible the follow-up of a host of about 300 couples - mother - child, offers us the opportunity to clarify certain determinants of the TMC of the HIV not officially elucidated by responding to the following question: Is there any relationship between the viral charge (in the plasma, cervico-vaginal secretaions in the breast milk) and the risk of transmission from mother to child of the HIV type1? Moreover the method of polymerase chain reaction (PCR), the yardstick for the precarious pedriatical diagnosis of the HIV infection is so complicated and onerous that its use in developing countries is bound to meet enormous obstacles. Thus the research question we will equally answer is : Is it possible to simplify for a more common use on the field in Africa the PCR method by lightening the procedures of blood sampling and the virological techniques ?

2.4. Geographical wones concerned
These two trials are made at the same time in two centers: Abidjan in Côte d'Ivoire, Center A and Bobo Dioulasso in Burkina Faso, Center B. The coordinating center for these two trials is INSERM n° 330 unit. University of Bordeaux II, France. The coordinator for the center in Abidjan is Dr Philippe Msellati and that of Bobo is Dr Nicolas Meda. The whole research program is named in Africa DITRAME project (The reduction of mother - child transmission of infections during pregnancy and breast feeding).

2.5. Acquired results
Counselling and testing units have been operational in Côte d'Ivoire and Burkina Faso and in MCH (SMI) since 1995. The rate of acceptability of the HIV tests is high but varies between 56% and 90% according to the area concerned. As at the date of 31st December 1995, among 2800 HIV tests made, the rate of general infection was at 12.1% (IC 95% , 9.5-12.5%). The proportion of women returning to the centers to get the test results varies from 45% to 80% according to the center concerned. The actual registration for the trials began in October 1995. By March 1996, 59 pregnant women had been registred for the ANRS 049a trials. The observance of the treatment and the assiduousness shown in the medical supervision visits were good. With these first group of women no anaemia and severe neutropenia, no important increase in transminases seriques were noticed in the results obtained on both mother and child after about six weeks of post-partum check of 37 mother-child couples. The average haemoglobine used in these trials was 9.6 g/dl. This average increased on the whole by 1.2 g/dl at the end of the treatment period fixed at 18 post-partum. The end of the two trials is December 1997.

2.6. Key words
mother to child transmission of HIV-1, AZT, prevention strategy, Burkina Faso, Côte d'Ivoire, chlorine of bensalkonium.

3. Publications.
MEDA N. Epidémiologie de la transmission mère-enfant du virus du sida dans les pays en développement. CIE : L'Enfant en Milieu Tropical 1996 : sous presse

VAN DE PERRE P, MEDA N. Interventions to reduce mother to child transmission of HIV. AIDS 1995; 9 (suppl A) : S59-S66.

CARTOUX M., MSELLATI P., MEDA N, et al. Acceptability of interventions to reduce perinatal HIV transmission in West Africa. In IXth International Conference on AIDS ans STD in Africa, Kampala, Uganda, 1995 : Abstract TuB 122.

CARTOUX M., MSELATTI P., MEDA N, et al. Acceptability of interventions to reduce mother to child transmission of HIV-1 in West Africa. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 1996 : in press.

DABIS F., MSELATTI P., MEDA N., WELFFREN-EKRA C., CARTOUX M.., MANDELBROT L. Zidovudine to decrease mother-to-child transmission of HIV-1 in Africa : an appraisal. In IXth International Conference on AIDS and STD in Africa, Kampala, Uganda, 1995 : Abstract TuC632.

SALAMON R., COULIBALY M., WELFFREN-EKRA C., MEDA N., OUANGO J-G. Pays en développement et recherche sur le SIDA : les problèmes éthiques. In IXth International Conference on AIDS and STD in Africa, 1995 : Abstract WeD240.

CARTOUX M., ROUAMBA O., MEDA N., DABIS F., DURAND G., SALAMON R. Le point sur le conseil lié au dépistage de l'infection par le VIH à Bobo-Dioulasso, Burkina Faso. Cahiers Santé 1996: 6 (1) : 7-10.

MEDA N., TOURÉ B., CARTOUX M., et al. Resons for refusing antenatal HIV testing in Burkina Faso. In IWth International Conference on AIDS and STD in Africa. Kampala, Uganda, 1995 : Abstract ThD293.

MEDA N., SOMBIE I., CARTOUX M., et al. HIV testing of pregnant women : acceptance of voluntary HIV secreening in Burkina Faso. In IXth International Conference on AIDS and STD in Africa, Kamapala, Uganda, 1995 : Abstract WeD839.

VAN DE PERRE P., MEDA N., DABIS F., et al. Possible interactions of brasfeeding with the efficacy of Zidovudine in reducing mother-to-child transmission of HIV-1. In IXth International Conference on AIDS and STD In Africa, Kampala, Uganda, 1995:Abstract TuC629.

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