JAIDS Journal of Acquired Immune Deficiency Syndromes:
The Haiti Research-Based Model of International Public Health Collaboration: The GHESKIO Centers
Pape, Jean W. MD*,†; Severe, Patrice D. MD†; Fitzgerald, Daniel W. MD*,†; Deschamps, Marie M. MD†; Joseph, Patrice MD†; Riviere, Cynthia MD†; Rouzier, Vanessa MD†; Johnson, Warren D. Jr MD*,†
*Center for Global Health, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, NY;
†Centres GHESKIO, Port-au-Prince, Haiti.
Correspondence to: Jean W. Pape, MD, CTU Les Centres GHESKIO, 33 Boulevard Harry Truman, Cite de l’Exposition, Port au Prince HT-6110, Haiti (e-mail: email@example.com).
Supported in part by grants from the National Institutes of Health: the National Institute of Allergy and Infectious Diseases to Dr Pape (UM1AI069421); the National Institute of Allergy and Infectious Diseases to Dr Fitzgerald (K24AI098627); the National Cancer Institute to Dr Fitzgerald (R01CA142422); the Fogarty International Center to Dr Johnson (D43TW000018); and the Fogarty International Center to Dr Pape (U2RTW006896); and the Fogarty International Center to Dr Fitzgerald (D43TW009606).
Presented in part at the 14th Conference on Retroviruses and Opportunistic Infections, February 25–28, 2007, Los Angeles, CA.
The authors have no conflicts of interest to disclose.
Abstract: For 3 decades, GHESKIO (the Groupe Haitien d’Etude du Sarcome de Kaposi et des Infections Opportunistes), the Haitian Ministry of Health, and Weill Cornell have pursued a tripartite mission of service, training, and translational research. The initial focus was on AIDS and tuberculosis. The mission has expanded to include the local community and now provides maternal–child health, family planning, cancer prevention and treatment, immunizations (including human papillomavirus, cholera), and primary education through vocational and microcredit programs. Outcome measures include a reduction in HIV prevalence from 6.2% to the current 2.2%, extensive tuberculosis and cholera prevention and treatment programs, and national training programs for biomedical and community health workers.
Haiti has some of the most challenging sociopolitical and economic problems in the world. The country has been affected by political instability and recurrent natural disasters.1,2 It is also one of the countries most affected by HIV/AIDS and tuberculosis (TB).3 Operational research has been essential to mount a successful response against these diseases.
In 1982, the Haitian Study Group on Kaposi Sarcoma and Opportunistic Infections (GHESKIO) was created with a mission of conducting operational research, training, and patient care for HIV/AIDS and associated infections. Thirty-one years later, Dr Kathleen Sebelius, the U.S. Health and Human Services Secretary, and Dr Florence Guillaume, the Haitian Minister of Health (MOH), summarized the role played by GHESKIO in Haiti by saying, “We expect GHESKIO to develop public health models that can be scaled-up at the national level.” How did GHESKIO acquire these credentials?
THREE DECADES OF HIV-RELATED RESEARCH IN HAITI
In 1980, we established the Cornell Unit at the State University Hospital in Port-au-Prince. With the introduction of oral rehydration solution and other measures, we were able to decrease the 40% in-hospital mortality rate for infants with acute diarrhea to less than 1% in the first year. In 1982, a national program for the control of diarrheal diseases was implemented with the Cornell Unit as the training site. The massive scale-up of this program is mainly responsible for the decrease in national infantile mortality from 144 per 1000 in 1980 to 60 per 1000 in 2000.4–7
In 1981, we were asked to evaluate adult patients with chronic diarrhea at the same hospital. These patients turned out to be the first cases with AIDS recognized in Haiti. In 1982, the U.S. Centers for Disease Control and Prevention listed Haitian race as a risk factor for HIV, causing unparalleled prejudice to Haitians.8–14 In 1983, GHESKIO published a comprehensive description of the first AIDS cases in a resource-poor setting.15 The story of HIV/AIDS in Haiti has since been inseparable from that of GHESKIO.
GHESKIO demonstrated that modes of HIV transmission among Haitians were the same as those of other nationalities, prompting the U.S. Centers for Disease Control and Prevention to remove Haitians from the so-called risk groups for AIDS.16–18 GHESKIO also showed that blood transfusions from paid donors were a major contributor to HIV transmission in Haiti, leading the MOH in 1986 to close all such blood banks and to put the Haitian Red Cross in charge of national blood banking operations.19
Chronic persistent diarrhea and pulmonary TB are the hallmarks of AIDS in Haiti. GHESKIO conducted seminal studies on the treatment and prevention of isosporiasis and cyclosporiasis.20–23 They also led the first trials documenting the protective effect of primary and secondary isoniazid prophylaxis in the prevention of active TB in coinfected patients.24,25 GHESKIO provides same-day TB diagnosis and treatment for patients with chronic cough who are coming for HIV testing after demonstrating that 30% of these patients had active TB.26 After documenting the role of sexually transmitted infections (STI) in enhancing HIV transmission, GHESKIO developed and scaled-up a syndromic STI guide that led to a marked decrease in STIs.27,28
These research findings led to the development of the GHESKIO comprehensive HIV prevention and care model that include nutritional support, access to primary and vocational schools, and microcredit loans, all offered at the same site.29 With the availability of international funding in 2003, the MOH asked GHESKIO to expand its model nationwide. GHESKIO's first 1000 patients on antiretroviral therapy (ART) had a 90% and 75% survival rate at 1 and 5 years, respectively, showing that resource-poor countries were capable of successful national ART scale-up.30,31 GHESKIO documented comparable survival rates in infants on ART.32 In 2005, GHESKIO evaluated the optimal timing for ART initiation and demonstrated that patients who initiated ART at the then recommended World Health Organization (WHO) guideline of CD4 <200 cells per cubic millimeter had 4-fold higher mortality and twice as many incident TB versus those who started at a CD4 count of <350 cells per cubic millimeter.33 This study prompted the WHO to revise their guidelines to recommend earlier initiation of ART.34
GHESKIO has also conducted many important maternal and child health studies (Figure 1). Our early studies described the accelerated progression to AIDS and death of HIV-infected infants and the role of bacterial sepsis in morbidity and mortality. GHESKIO pioneered early infant diagnosis with polymerase chain reaction in 2009 and an ultrasensitive p24 antigen assay. We also evaluated different ART regimens to reduce acquisition of nevirapine resistance after single dose nevirapine prophylaxis for the prevention of mother-to-child transmission of HIV. In nutrition, a 6-month program for feeding HIV-exposed infants with nutritional supplements and other support was associated with a reduced risk of growth faltering.35 This intervention is now being adapted and scaled-up in other settings. Breast milk composition of HIV-infected mothers is being assessed for its impact on the infant gut microbiome and immune development. GHESKIO has also evaluated the logistics and cost for implementing a national, rapid, test-and-treat program for syphilis and the cost of HIV treatment programs.36–39 The MOH has since initiated a national program to eradicate congenital syphilis. GHESKIO and the MOH conducted the first national study on the incidence of multidrug-resistant tuberculosis (MDR-TB) in Haiti, showing a rate of 3% in persons without previous TB treatment.40,41 In 2008, GHESKIO was approved by the WHO Green Light Committee as 1 of only 2 MDR-TB treatment centers in Haiti, with Partners in Health.
GHESKIO has sought to achieve an impeccable record of ethical research in Haiti. We have had an institutional review board in place since 1984. In 2001, GHESKIO promoted the development of Haiti's first National Bio-Ethics Committee.42–44 In addition, GHESKIO has pioneered many interventions to improve the understanding of illiterate volunteers enrolled in research studies.45–49
Community involvement and direct participation have been central for the conduct of research and its implementation into services and training. GHESKIO has an effective and diverse 22-member community advisory board (CAB) representing all sectors of society. GHESKIO's new frontier is focused on adolescents and young adults, and an adolescent CAB has been established to facilitate interventions aimed at reducing vulnerability and stigma in this population.
IMPACT OF THE EARTHQUAKE AND THE CHOLERA EPIDEMIC
GHESKIO's response to public health emergencies in Haiti demonstrates its resilience and capacity to refocus rapidly on new emerging health priorities. Although GHESKIO lost many key personnel and 65% of its facilities in the earthquake, they managed to locate and continue treatment on 94% of patients on ART within 3 weeks of the earthquake. At the same time, GHESKIO set up an emergency field hospital in collaboration with U.S. Health and Human Services Disaster Medical Assistance Team that performed surgical procedures on more than 3000 patients. GHESKIO provided postoperative and rehabilitation services to 8000 patients over the ensuing 2 years and assistance to more than 7000 internally displaced persons.50–54
In October 2010, Haiti experienced its first cholera epidemic. GHESKIO rapidly established cholera treatment centers inside the adjacent slums, trained 2000 medical staff, and informed 250,000 persons in the community about modes of cholera prevention and treatment.55,56 As of June 2013, more than 33,000 patients were admitted to the GHESKIO cholera treatment sites with 0.1% mortality. In collaboration with the MOH and Partners in Health, GHESKIO successfully introduced oral cholera vaccine to 52,000 high-risk persons in urban slums in Port-au-Prince (Rouzier et al and Valcin et al, unpublished data).57,58 The MOH has since launched a national oral cholera vaccine scale-up (Figure 2).
THE CURRENT SITUATION
GHESKIO has been a major partner with the government and other organizations in combating the HIV epidemic for more than 30 years. The HIV prevalence in Haiti has decreased, from 6.2% in 1993 to 2.2% in 2012.7 Over the past decade, ART has been expanded to 123 clinics providing treatment to more than 50,000 patients, with one third of these covered by the GHESKIO network. Using the WHO criteria of CD4 counts of <350 cells per cubic millimeter to initiate ART, Haiti has already achieved universal access.
As of June 2013, GHESKIO had trained more than 11,000 medical personnel in integrated HIV prevention and care, including 3500 physicians, 4900 nurses, 1750 laboratory technicians, and 1375 social workers. A diversified CAB has sensitized more than 300,000 community agents and leaders about HIV modes of transmission. Three specialized training programs have been established: Haiti's first Master's in Public Health Program in 2005, the first Nurse Practitioner Program in 2009, and a specialized laboratory training course in 2010. These programs are successful because they fulfilled the needs of expanding human resources and were developed in collaboration with local and international institutions: the Master's in Public Health Program and Nurse Practitioner Program with Quisqueya and Cornell Universities, and the specialized laboratory training course with the National Public Health Laboratory.
GHESKIO has been a model of US-international collaboration. GHESKIO research evolved from early epidemiologic and natural history studies to the conduct of clinical trials supported by the National Institutes of Health (NIH) Method to Extend Research in Time Award (1990).59–61 GHESKIO was designated an international site in the HIV Vaccine Trial Network (1997) and in the Adult Clinical Trial Group (2002) and as an independent Clinical Trials Unit (CTU) in 2006. GHESKIO's productivity has been recognized by uninterrupted NIH support since 1983. The GHESKIO CTU has conducted 7 adult therapeutic, 9 HIV vaccine, and 4 maternal-child-adolescent trials with 3400 participants enrolled and retention rates of 98%. GHESKIO is currently conducting 17 investigator-initiated research projects independent of the CTU. To date, there have been more than 150 peer-reviewed publications with seminal studies published in prestigious journals. In 2000, GHESKIO was given the status of “public utility” by the Haitian government.62
GHESKIO is presently implementing an NIH study to provide same-day HIV diagnosis and ART initiation, with the possibility to expand a test-and-treat intervention nationally. GHESKIO has also determined the most common human papillomavirus serotypes in both HIV-infected and uninfected women and plans to conduct a pilot project with the MOH to offer human papillomavirus vaccine to adolescents in an urban population. The increasing number of MDR-TB cases is a major concern and a priority. GHESKIO plans to evaluate new drugs and vaccines and is supported by its BSL-3 laboratory and a new MDR-TB hospital. Nutrition and maternal-child health continue to be other focus areas with the construction of a Family Nutrition Unit. A 2007 editorial of the Journal of Infectious Diseases stated, “Operational research must be a cornerstone of future success (of AIDS interventions), and it is expected that the GHESKIO program will continue to help lead the way”.63
The authors acknowledge the following for their contributions: Dr Peter F. Wright from Dartmouth (HIV vaccine trials and pediatric studies); Dr Serena Koenig from Harvard (cost studies and multi-drug resistant tuberculosis interventions); Dr Rose Irene Verdier (regulatory and ethics); Dr Daphnee Benoit (training); Mrs Marie-Eugenie Beaulieu, Alexandra Apollon, and Oksana Ocheretina (laboratory); Adias Marcelin, Christian Perodin, and Reginal Osse (data management); Drs Mireille Peck and Maguy Colin (CAB); and Claudia Riche and Yonie Cadot (nursing).
4. Pape JW, Mondestin B, Jasmin L, et al.. Management of diarrhea in Haiti: mortality reduction in 8,443 hospitalized children. In: Proceedings of the WHO International Conference on Oral Rehydration Therapy. Washington, DC; 1983:87–89.
5. Pape JW, Balasubramanyan R, Rohde JE. Intestinal illness. In: Sandler RA, Jones TC, eds. Medical Care of Refuges. New York, NY: Oxford University Press; 1988:364–373.
6. Mortalité Enquête;, Morbidité et Utilisation des Services - EMMUS-IV, Rapport Préliminaire, HAÏTI, 2005. l’Institut Haïtien de l’Enfance (IHE) with the collaboration of l’Institut Haïtien de Statistique et d’Informatique (IHSI). Port-au-Prince, Haiti; 2005.
7. Mortalité Enquête;, Morbidité et Utilisation des Services - EMMUS-V, Rapport Préliminaire, HAÏTI, 2012. l’Institut Haïtien de l’Enfance (IHE) with the collaboration of l’Institut Haïtien de Statistique et d’Informatique (IHSI). Port-au-Prince, Haiti; 2012.
8. Centers for Disease Control and Prevention. Current trends update on acquired immune deficiency syndrome (AIDS)—United States. MMWR Morb Mortal Wkly Rep. 1982;31:507–508, 513–514. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00001163.htm
. Accessed June 1, 2013.
9. Moskowitz LB, Kory P, Chan JC, et al.. Unusual causes of death in Haitians residing in Miami. High prevalence of opportunistic infections. JAMA. 1983;250:1187–1191.
10. Jaffe HW, Bregman DJ, Selik RM. Acquired immune deficiency syndrome in the United States: the first 1,000 cases. J Infect Dis. 1983;148:339–345.
11. Pitchenik AE, Fischl MA, Dickinson GM, et al.. Opportunistic infections and Kaposi's sarcoma among Haitians: evidence of a new acquired immunodeficiency state. Ann Intern Med. 1983;98:277–284.
13. Farmer PE, ed. AIDS and Accusation. Berkeley, CA: University of California Press; 1992.
14. Pape JW, Liautaud B, Thomas F, et al.. Characteristics of the acquired immunodeficiency syndrome (AIDS) in Haiti. N Engl J Med. 1983;309:945–950.
15. Pape JW, Liautaud B, Thomas F, et al.. The acquired immunodeficiency syndrome in Haiti. Ann Intern Med. 1985;103:674–678.
16. Pape JW, Liautaud B, Thomas F, et al.. Risk factors associated with AIDS in Haiti. Am J Med Sci. 1986;291:4–7.
17. Pape JW, Stanback ME, Pamphile M, et al.. Prevalence of HIV infection and high-risk activities in Haiti. J Acquir Immune Defic Syndr. 1990;3:995–1001.
18. Pape JW, Johnson WD Jr. Epidemiology of AIDS in the Caribbean. In: Piot P, Mann J, eds. Baillier's Clinical Tropical Medicine & Communicable Diseases. Vol. 3. London, United Kingdom: Bailliere Tindall Limited, Harcourt Brace Jovanovich, 1988:31–42.
19. Centers for Disease Control and Prevention. Current trends update: acquired immunodeficiency syndrome United States. MMWR Morb Mortal Wkly Rep. 1985;34:245–248.
20. DeHovitz JA, Pape JW, Boncy M, et al.. Clinical manifestations and therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1986;315:87–90.
21. Pape JW, Verdier R-I, Johnson WD. Treatment and prophylaxis of Isospora belli
infection in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1989;320:1044–1047.
22. Pape JW, Verdier RI, Boncy M, et al.. Cyclospora infection in adults infected with HIV. Clinical manifestations, treatment, and prophylaxis. Ann Intern Med. 1994;121:654–657.
23. Verdier RI, Fitzgerald DW, Johnson WD Jr, et al.. Trimethoprim-sulfamethoxazole compared with ciprofloxacin for treatment and prophylaxis of Isospora belli
and Cyclospora cayetanensis
infection in HIV-infected patients. A randomized, controlled trial. Ann Intern Med. 2000;132:885–888.
24. Pape JW, Jean S, Ho J, et al.. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet. 1993;342:268–272.
25. Fitzgerald DW, Desvarieux M, Severe P, et al.. Effect of post-treatment isoniazid on prevention of recurrent tuberculosis in HIV-1 infected individuals: a randomized trial. Lancet. 2000;356:1470–1474.
26. Burgess AL, Fitzgerald DW, Severe P, et al.. Integration of tuberculosis screening at an HIV voluntary counseling and testing center in Haiti. AIDS. 2001;15:1875–1879.
27. Deschamps MM, Pape JW, Hafner A, et al.. Heterosexual transmission of HIV in Haiti. Ann Intern Med. 1996;125:324–330.
28. Mellon RL, Liautaud B, Pape JW, et al.. Association of HIV and STDs in Haiti: implications for blood banks and HIV vaccine trials. J Acquir Immune Defic Syndr. 1995;8:214.
29. Peck R, Fitzgerald DW, Liautaud B, et al.. The feasibility, demand and effect of integrating primary care services with HIV voluntary counseling and testing: evaluation of a 15-year experience in Haiti, 1985-2000. J Acquir Immune Defic Syndr. 2003;33:470–475.
30. Severe P, Leger P, Charles M, et al.. Antiretroviral therapy in a thousand patients with AIDS in Haiti. New Eng J Med. 2005;353:2325–2334.
31. Leger P, Charles M, Severe P, et al.. Five-year survival of patients with AIDS receiving antiretroviral therapy in Haiti. N Engl J Med. 2009;361:828–829.
32. George E, Noel F, Bois G, et al.. Antiretroviral therapy for HIV-infected children in Haiti. J Infect Dis. 2007;195:1411–1418.
33. Severe P, Jean Juste MA, Ambroise A, et al.. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med. 2010;363:257–265.
35. Heidkamp RA, Stoltzfus RJ, Fitzgerald DW, et al.. Growth in late infancy among HIV-exposed children in urban Haiti is associated with participation in a clinic-based infant feeding support intervention. J Nutr. 2012;142:774–780.
36. Schackman BR, Neukermans CP, Fontain SN, et al.. Cost-effectiveness of rapid syphilis screening in prenatal HIV testing programs in Haiti. PLos Med. 2007;4:e183.
37. Koenig SP, Riviere C, Leger P, et al.. The cost of antiretroviral therapy in Haiti. Cost Eff Resour Alloc. 2008;6:3.
38. Koenig S, Schackman B, Riviere C, et al.. Clinical impact and cost of monitoring for asymptomatic laboratory abnormalities among patients receiving antiretroviral therapy in a resource-poor setting. Clin Infect Dis. 2010;51:600–610.
39. Koenig SP, Bang H, Severe P, et al.. Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti. PLos Med. 2011;8:9.
40. Joseph P, Sévère P, Ferdinand S, et al.. Multi-drug resistant tuberculosis at an HIV testing Center in Haiti. AIDS. 2006;20:415–418.
41. Ocheretina O, Morose W, Gauthier M, et al.. Multidrug-resistant tuberculosis in Port-au-Prince, Haiti. Rev Panam Salud Publica. 2012;31:221–224.
42. Pape JW. Institution review boards: consideration in developing countries. Emerg Infect Dis. 2001;7:547.
43. Fitzgerald DW, Wasunna A, Pape JW. Ten questions institutional review boards should ask when reviewing international clinical research protocols. IRB. 2003;25:14–28.
44. Fitzgerald DW, Wasunna A, Crigger B, et al.. Building ethics capacity in Haiti. Dev World Bioeth. 2003;3:3–9.
45. Fitzgerald DW, Marotte C, Verdier RI, et al.. Comprehension during informed consent in a less-developed country. Lancet. 2002;360:1301–1302.
46. Joseph P, Schackman B, Horowitz R, et al.. The use of an educational video during informed consent in an HIV clinical trial in Haiti. J Acquir Immune Defic Syndr. 2006;42:588–591.
47. Fitzgerald DW, Maxi A, Marcelin A, et al.. Notification of positive HIV test results in Haiti: can we better intervene at this critical crossroads in the life of HIV-infected patients in a resource-poor country? AIDS Patient Care STDs. 2004;18:658–664.
48. Horwitz RH, Roberts LW, Seal DW, et al.. Assessing whether consent for a clinical trial is voluntary. Ann Intern Med. 2013;158:222–224.
49. Fitzgerald DW, Pape JW, Wasserheit JN, et al.. Provision of treatment in HIV-1 vaccine trials in developing countries. Lancet. 2003;20:993–994.
50. Pape JW, Johnson WD, Fitzgerald DW. The earthquake in Haiti—dispatch from Port-au-Prince. N Engl J Med. 2010;362:575–577.
51. Pape J. Global health. Haiti’s quake shifts clinic’s focus from AIDS to aid. Science. 2010;327:509.
52. Hopmeier M, Pape JW, Paulison D, et al.. Reflections on the initial multinational response to the earthquake in Haiti. Popul Health Manag. 2010;13:3.
53. Pape JW, Deschamps MM, Ford H, et al.. The GHESKIO refugee camp after the earthquake in Haiti—dispatch 2 from Port-au-Prince. N Engl J Med. 2010;362:e27.
54. Pape JW, Rouzier V, Ford H, et al.. The GHESKIO field hospital and clinics after the earthquake in Haiti—dispatch 3 from Port-au-Prince. N Engl J Med. 2010;362:e34.
55. Farmer P, Almazor CP, Bahnsen ET, et al.. Meeting cholera’s challenge to Haiti and the world: a joint statement on cholera prevention and care. PLos Neg Trop Dis. 2011;5:e1145.
56. May JP, Joseph P, Pape JW, et al.. Health care for prisoners in Haiti. Ann Intern Med. 2010;153:407–410.
57. Hinman A, Farmer P, Ivers LC, et al.. Cholera vaccination in Haiti: evidence, ethics, experience. Harv Int Rev. 2011;33:51–57.
58. Ivers L, Pape JW, Farmer P. Oral cholera vaccine and integrated cholera control in Haiti. Lancet. 2012;379:2026–2028.
59. Deschamps MM, Fitzgerald DW, Pape JW, et al.. HIV infection in Haiti: natural history and disease progression. AIDS 2000;14:2515–2521.
60. Deschamps MM, Pape JW, Desvarieux M, et al.. A prospective study of HIV seropositive asymptomatic women of childbearing age in a developing country. J Acquir Immune Defic Syndr. 1993;6:446–451.
61. Jean SS, Pape JW, Verdier RI. The natural history of human immunodeficiency virus 1 infection in Haitian infants. Ped Infect Dis J. 1999;18:58–63.
62. Moniteur Le. Jounral Officiel de la Republique d’Haiti. 2000;71.
63. Adams LV, Columbo P. The time to treat children is now. Editorial Comentary. J Infect Dis. 2007;195:1396–1398.
HIV infection; Haiti; cholera
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