Collaboration between Harvard University (USA) and
Université Cheikh Anta DIOP  (Senegal).

1. Introduction

In the past few years, Senegal has been praised as a country that has been able to contain its HIV epidemic, with a current prevalence of 1.4% of the total population.  This relatively low prevalence is certainly due to many different factors, including positive government action.  Early on in the epidemic, the government installed a National AIDS Prevention Committee and was supportive of AIDS research in the country.  Senegal has also involved its religious leaders and communities in the fight against AIDS. Researchers from Harvard University have been collaborating with colleagues in Senegal for over 15 years in many areas relating to HIV/AIDS prevention.  The experience and knowledge gained through this collaboration will be invaluable resources for the APIN project.

In recognition of their commitment in the fight against AIDS in their countries, Presidents Yoweri Museveni of Uganda and Abdou Diouf of Senegal received excellence awards at the seventh conference of the Society for Women and AIDS in Africa (SWAA), held in Dakar last December. Sustained preventive information campaigns and services have brought HIV infection rates down from double to single-digit levels in Uganda and kept infection rates extremely low in Senegal. View the United Nations report on HIV control measures in Senegal and Uganda.

2. Information on Senegal

Area: 196,190 sq km  

Capital:  Dakar

Population: 9 million
Density: 47 per sq km
Growth: 3.32% per year

Coastline: 531km

3. The Inter-University Convention.

The collaboration between Harvard University and Université Cheikh Anta Diop of Dakar (Senegal) had its beginnings even before AIDS itself was identified.  In 1979, Max Essex, Chairman of the Department of Cancer Biology at the Harvard School of Public Health, attended a workshop in Senegal on a potential Hepatitis B vaccine.  His commitment to the country grew, and in 1985 he joined with Souleymane Mboup of the Université Cheikh Anta Diop and researchers from the Universitiés of Tours and Limoges (France) to create the present collaboration for HIV/AIDS research and prevention, named Inter-University Convention Dakar-Tours-Limoges-Boston.  Since its inception in 1985, the convention has remained particularly strong between Harvard University in Boston and the Université Cheikh Anta Diop in Dakar.  This joint collaboration has given rise to the longest prospective study on HIV in Africa and one of the longest studies of HIV-infected people in the world, while helping to develop local infrastructure in Dakar.  Today, the laboratory of Professor S. Mboup has grown into one of the largest and most advanced AIDS biomedical facility in West Africa.  In 1993, the Harvard AIDS Institute (HAI) was created. HAI is a university-wide organization that conducts and catalyzes research to stop the worldwide AIDS epidemic. Members of HAI and research scientists from the Department of Immunology and Infectious Diseases at the Harvard School of Public Health form the core of the Boston team in this collaboration. The researchers combine biologic research with epidemiologic and clinical studies to help uncover clues to the two AIDS viruses, HIV-1 and HIV-2.  While they expect their research to hasten the eventual eradication of both AIDS viruses, the researchers also try to integrate their work with prevention and treatment of these viral infections in West Africa.  The formal agreement of the Convention, among the institutions, states that research results will be integrated with prevention measures for HIV-1, HIV-2, and other sexually transmitted infections in Senegal.

The AIDS collaboration takes as its symbol the Baobab tree, which to the Senegalese represents both life and death:

4. Scientific breakthroughs

The joint collaboration has yielded several important findings since 1985, including the initial identification of the second AIDS virus (human immunodeficiency virus type 2, or HIV-2), which has been confined primarily to West Africa.  The research teams have also shown that the rates of disease development and transmission are dramatically slower in people with HIV-2 than in people with HIV-1, the virus causing the worldwide AIDS epidemic.  These observations then led to the idea that the weaker and less easily transmissible virus might protect against HIV-1 infection. In 1995, these teams reported that infection with HIV-2 sharply reduces the chances of becoming infected with HIV-1.  This finding demonstrated for the first time in humans that protection against HIV-1 infection is possible, and may have important implications for AIDS vaccine development. The study was performed among 756 women licensed as commercial sex workers in Dakar, from 1985 to 1994.  The researchers found that infection with HIV-2 reduced the women's chances of acquiring HIV1 infection by approximately 70%.  This reduction occurred despite a higher incidence of gonorrhea, which suggests that the HIV-2 infected women had not lessened their exposure to HIV-1 through behavioral change.

In addition to findings relating to the biology and natural history of HIV-1 and HIV-2, the collaboration has also fomented the development of technologies pertinent to the study of these viruses in West Africa.  For example, a serological test screening simultaneously for HIV-1 and HIV-2 was developed in Professor Phyllis Kanki's laboratory, and costs a fraction of the available commercial assays. Many HIV-2 specific research reagents where also developed by the Kanki laboratory, including a viral load assay for this less-studied virus.  As no commercial assay for HIV-2 viral load is currently available, this assay will be essential to many research and clinical applications.

5. Description of Projects and sites : Dakar, Kaolack and Ziguinchor

Senegal is a country of approximately 9 million inhabitants.

Initial cross-sectional survey data (1985-1987) showed a variable distribution of HIV and demographic characteristics in the registered female prostitutes from these cities.

In 1970, the government of the Republic of Senegal instituted a program for the registration of self-identified female prostitutes, legalizing their practice of providing sex for payment.  This program required semi-annual evaluation and treatment, if necessary, for sexually transmitted diseases at clinic centers established for this purpose in Dakar (1970), Kaolack (1987), and Ziguinchor (1987).  Venous blood samples were routinely taken at annual intervals to assess serologic status.  These centers originally managed by social workers and nurse practitioners were joined by our study physicians in Dakar (1985), Kaolack (1987), and Zinguinchor (1987).  This allows for a more complete physical examination but also more extensive clinical assessment at scheduled and nonscheduled visits.   All registered prostitutes visiting the clinics are asked to participate in our studies.  they are asked to sign an inform consent form and to complete a basic socio-demographic questionnaire.  Irrespective of enrollment in our studies, all prostitutes attending the clinic are counseled by physicians and social workers on the prevention of sexually transmitted diseases including AIDS.  Free condoms are provided at each visit, and women are instructed on their use.  On subsequent visits, women are counseled again on condom use.  This infrastructure has enabled the researchers to track first the spread of HIV-2 through this population, then the spread of the later and faster moving HIV-1 which has been the basis for many research studies.

Brief description of sponsored projects in Senegal:

5.1 - Natural History of HIV Infections in Senegal (Prostitute Project):

One of the first prospective study to be initiated by the collaboration, this study was undertaken to identify and compare the risk determinants for both HIV-1 and HIV-2 in the same self-identified high-risk group.  The prospective nature of the study and the positive identification of seroconversion events allowed for the comparison of disease progression between HIV-1 and HIV-2 infected subjects.  Through this study, it has been found that the rate of AIDS development is >10 fold higher in HIV-1 compared to HIV-2.  Also, it was found that HIV-2 is less transmissible compared to HIV-1, both by perinatal and heterosexual routes.  HIV-2 thus appears to be less virulent than HIV-1.

5.2 - Project 1: Natural History of Perinatally Acquired HIV

5.3 - Project 2: Natural History of Disease Patient Study

5.4 - Natural Protection

5.5 - FHI/Pave

5.6 - Primary infection

5.7 - Kaolack project / Dr. Laura Leonard.

6. Education, Training and Technology Transfer

The collaboration has a training component sponsored by the Fogarty International Center of the National Institutes of Health.  Under this training grant, Senegalese researchers have had the opportunity to spend time at the Harvard School of Public Health, either as research fellows or as students enrolled in degree-granting programs (D.Sc, PhD, M.Sc).  During that time, the trainees have the opportunity to access the vast resources offered not only by the School of Public Health but also by other faculties at Harvard, in all the different areas of expertise that might be relevant for HIV/AIDS prevention.

Researchers from the Harvard School of Public Health have been going regularly to Senegal as well, to help train local personnel and help with technology transfer.  In addition, various training workshops have been organized in Dakar over the years, addressing various issues of HIV research:

Select Workshops in Senegal:

Applications of Polymerase Chain Reaction (PCR) in HIV Pathogenesis Research (Dakar, September 14-16, 1992)

Computer Skills and Data Management Colloquium (Dakar, April 19-23, 1993)

In vitro Antibody Production in HIV Pathogenesis Research (Dakar,  February 13-17, 1995)

Mucosal Immunity in HIV Infection workshop (Dakar, May 15-19, 1995)
Cytotoxic T-Lymphocyte workshop (Dakar, October 16-20, 1995)

List of Forgarty International Fellows from Senegal :

Cheikh Saad Boye, Jean Louis Sankale, Aissatou Gueye NDiaye, Tidiane Ndoye, Ibou Thior, Abdoulaye Dieng Sarr, Khady Diouf, Mame Awa Toure.

7. Select Publications

Lower Human Immunodeficiency Virus (HIV) Type 2 Viral Load Reflects the Difference in Pathogenicity of HIV-1 and HIV-2.
J. Infect. Dis. 180(4):1116-21,1999.
Popper, S., Dieng-Sarr, A., Travers, K.U., Guèye-Ndiaye, A., Mboup, S., Essex, M.E., and Kanki, P.J.

Human immunodeficiency virus type 1 subtypes differ in disease progression.
J. Infect. Dis. 179(1):68-73,1999.
Kanki PJ. Hamel DJ. Sankale JL. Hsieh Cc. Thior I. Barin F. Woodcock SA. Gueye-Ndiaye A. Zhang E. Montano M. Siby T. Marlink R. NDoye I. Essex ME. MBoup S.

Role of the CCR5 delta 32 allele in resistance to HIV-1 infection in west Africa.
J Hum Virol 1998 Nov-Dec;1(7):469-74.
Kokkotou E, Philippon V, Gueye-Ndiaye A, Mboup S, Wang WK, Essex M, Kanki P.

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.
AIDS. 12(2):131-7, 1998 Jan 22.
Sarr AD. Hamel DJ. Thior I. Kokkotou E. Sankale JL. Marlink RG. Coll-Seck EM. Essex ME. Siby T. NDoye I. Mboup S. Kanki PJ.

Natural protection against HIV-1 infection provided by HIV-2.
Science 1995;268:1612-15.
Travers K, Mboup S, Marlink R, Guèye-Ndiaye A, Siby T, Thior I, Traoré I, Dieng-Sarr A., Sankalé JL, Mullins C, NDoye I, Hsieh C, Essex M, and Kanki P.

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.
Science 1994;265:1587-90.
Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traore I, Hsieh C-C, Dia M, Gueye E-H, Hellinger J, Gueye-Ndiaye A, Sankale J-L, Ndoye I, Mboup S, and Essex M.

8. WEB LINKS

Senegalese Government (in French)

Senegalese Ministry of Health (in French)

HIV in Senegal

Harvard School of Public Health

Harvard HIV Research Labs


Harvard AIDS Institute