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*,†
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).
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