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Health Impact of Research in the Caribbean

Health Impact of Research in the Caribbean. Jean William Pape, MD Director Centres GHESKIO , Port-au-Prince, Haiti Professor of Medicine, Weill Medical College of Cornell University, New York, NY, USA A Multicultural Caribbean United Against HIV/AIDS Meeting

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Health Impact of Research in the Caribbean

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  1. Health Impact of Research in the Caribbean Jean William Pape, MD Director Centres GHESKIO , Port-au-Prince, Haiti Professor of Medicine, Weill Medical College of Cornell University, New York, NY, USA A Multicultural Caribbean United Against HIV/AIDS Meeting Santo Domingo, Dominican Republic, March 4-7, 2004

  2. Objective and Methods • Objective: • Identify specific research projects conducted in the Caribbean that had an impact on care and or public health • Methods: • Gather original research studies conducted in the Caribbean and published in peer-reviews : • Very difficult task: No common data source for the region. • A data base was sent to key researchers in the region • Obtain from key researchers their opinion about the impact of such research on care and or public health in their respective country, the region, the world • Limitations: • Omissions by • Lack of data • Lack of time • Focus on biomedical research

  3. The Many Faces of the Caribbean • > 30 Countries/territories varying in size, populations, development, ethnicity, culture. • Territorial extent • Sovereign state members of CARICOM including • Belize (Central America), • Guyana, Surinam (South America) • Haiti • The French territories: Martinique, Guiana, Guadeloupe • Semi-autonomous states of the Kingdom of the Netherlands • Cuba and The Dominican Republic • Puerto-Rico and the US Virgin Islands

  4. The AIDS Epidemic in the Caribbean • 2nd most affected region in the world • National HIV seroprevalenve varies widely • 0.02% in Cuba to 3-5% in Haiti • > 1% in at least 12 countries (UNAIDS) • > 2% in at least 8 countries (UNAIDS) • Island of Hispagniola: epicenter : 75% • Haiti: 55% • Dominican Republic: 20%

  5. Distribution of HIV-1 Subtype in the Caribbean • HIV-1 • Predominance of Type B • Others subtypes: • Cuba: C, D, F, G, H, J, and recombinants Cueves et al 2002 • Martinique: A Ouka et al, 1998 • French Guiana, A, F Kazanji et al 2001 • Puerto-Rico: D, B/F, Flores et al 1999 • Trinidad/T: • B , Trinidad-variant Cleghorn et al 2000 • D Camara B, 2003 • No HIV-2 documented • References: Cesaire R, Cleghorn F, Camara B

  6. History of HIV/AIDS in the Caribbean • USA: • 1981: 1st cases of KS and PCP MMWR 1981:30:305-8 • 1982: KS and OI among Haitians MMWR 1982:31:353-61 • Haiti: • KS (1979): 11 cases:Liautaud B. Ann Dermatol. Venerol. 1983 110,213-219 • OI (1978): 90 cases: Pape JW. N. Engl.J.Med 1983 309:945-50; Malebranche R Lancet 1983 1:873-8 • Trinidad/Tobago: • OI (1983) 2 cases MSM: Bartholomew C. W.I.Med.J 1983 32;177-180 • Jamaica: • OI (1982): 1 case MSM: Narain JP.PAHO Bull 1989;61-71,1989 • Bermuda/Puerto-Rico: (1982) • Earliest cases: Ken Castro, MMWR (1982)

  7. Characteristics of Tropical AIDS • Constitutional S/S: • Fever and severe weight loss • GI: • Oral thrush/dysphagia (candida albicans; CMV) • Chronic/intermittent diarrhea (cryptosporidium sp.; Isospora belli;cyclospora cayentanensis) • Pulmonary • Mycobacterium tuberculosis • Skin: • Pruritic skin lesions (prurigo) Liautaud B. Arch Derm (1989) 125:629-32 • Trinidad:Histoplamosis. Barton EN et al. J trop Geo Med. 1988. 40:153-157 • Pape JW et al. N.Engl J Med 1983 309:945-50 • Malebranche R et al. Lancet 1983 1:873-8

  8. Clinical Manifestations and Therapy of Isospora Belli in AIDS Patients Pape et al. NEJM 320:1044, 1989DeHovitz et al. NEJM 315:87, 1986

  9. Cyclospora Infection in Adults Infected with HIV Pape JW et al. Ann Int Med 1994 121:654 Verdier RI et al. Ann Int Med , 2000 132:885-888.

  10. Risk of Tuberculosis • Among Persons coming for HIV Screening • Dominican Republic: • 10% of all comers have active TB Espinal MA et al. Lancet.1995;354:890-93 • Haiti: • 6% of all comers have active TB and • 33% of all those with cough have active TB. Burgess A et al. AIDS 2001.15:1875-79 Same Screening, diagnosis, treatment and prevention of TB • Infectiousness of M. tuberculosis in HIV-infected: • Dominican Republic: HIV+ compared to HIV- are less likely to transmit M. tuberculosis to their close contacts Espinal MA et al. Lancet.2000,355:275-280

  11. Tuberculosis prevention in persons co-infected with HIV and TB Rate of active tuberculosis cases per 100 person-years Placebo Intervention Author/Place/Date Pape et al/Haiti/ The Lancet 342: 1993 INH, X 1 year 10 1.7 Markowitz et al/USA/1997 INH, X 6 mo 4.7 1.6 Whalen et al/Uganda/1997 INH, X 6 mo 3.41 1.08 INH+RIF, X 3 mo 3.41 1.32 INH+RIF+PZA, X 3 mo 3.41 1.73 Halsey et al/Haiti/1999 INH, 2X/week, X 6 mo - 1.0 RIF +PZA , X 8 weeks - 3.7 INH = Isoniasid ;RIF = Rifampin; PZA = Pyrazinamide

  12. Effect of Preventive INH on the Incidence of Active TB and Progression of HIV infection Pape JW et al: The Lancet 342: 1993

  13. Clinical Outcome of HIV-infected patients treated for Tuberculosis with regimens containing Rifampicin outcome % *% dead since diagnosis versus % dead during therapy for tuberculosis **DOT 6 months of intermittent thrice weekly regimen of 2HRZE/4 HR *+ Modified DOT 2HRZ/4HR

  14. TB Recurrence in HIV+ and HIV – Patients Successfully Treated for TB Proportion free of recurrent tuberculosis Time from completion of TB therapy (months) Fitzgerald D et al. The Lancet 2000 356 : 1470-74

  15. Effect of Post Treatment Isoniazid Prophylaxis on TB Recurrence among HIV+ Patients Proportion free of recurrent tuberculosis Population free of recurrent tuberculosis Time from completion of TB therapy (months) Fitzgerald D et al. The Lancet 2000 356 : 1470-74

  16. HIV-1 Association with HTLV-1 • Prevalence of HTLV-1: 2-5% in population of African ancestry in the region, with low diffusion into non-African derived Caribbeans • Impact of HTLV-1 on natural history of HIV-1 • Trinidad: • Associated with a rapid progression to AIDS in a small study. Bartholomew C et al.Lancet 1987, 2:8573:1469; Cleghorn F et al Arch Int. Med.1992, 152:1372-73. 2001,17:799-805 • Impact of HIV-1 on the natural history of HTLV-1 • Martinique: • HIV-1 does not increase viral load of HTLV-1. Cesaire, R et al AIDS Res Hum Retro. 2001,17:799-805 • Both teams: CD4 counts could be artificially increased

  17. Changing Pattern of AIDS: Increased Heterosexual Transmission HAITI TRINIDAD/TOBAGO Pink= homo/bisexual; White= heterosexual/probable heterosexual; Red =blood transfusion; Green=IVDA Pape, J.W. and Johnson, W.D., Jr.:. In: Baillier's Clinical Tropical Medicine & Communicable Diseases, 3, 1988, . 31-42.; Cleghorn F et al AIDS. 1995.9:389-394

  18. Risk Factors for HIV/AIDS • Introduction of HIV by • MSM in Haiti, Jamaica, Trinidad/Tobago documented by molecular epidemiological analysis (T/T) • Also migrant farm workers, FCSWS, and informal commercial importers in Jamaica: Figueroa PJ et al AIDS.1995,9:761-8 • Sexual Transmission: 75% and driven by FCSWs • Heterosexual: > 70% • MSM: 5% • Blood Transfusion: < 5% • Mother to Child Transmission (MTCT): 5% • IVDU rare except for Puerto-Rico Deren et al Int Conf AIDS 1998: 12:242 AIDS Epidemic Update, UNAIDS report, December 2003

  19. Cofactors of Heterosexual Transmission • Biologic • STI • Lack of circumcision: Halperin D • Dry sex: Halperin D. Sex Transm Inf 1999,75:445-446 • Genital discharge (Bacterial vaginosis/candida) • Behavioral/cultural • Other • Poverty • Migration • Tourism

  20. STI as Cofactors for HIV transmission • Two of the earliest epidemic of crack/cocaine (1982) followed by an epidemic of GUD and an epidemic of heterosexually transmitted HIV occurred in: • Trinidad/Tobago Cleghorn F et al AIDS 1995.9:4: 389-94 • The Bahamas Gomez P et al Sex Trans Dis. 2002,259-264 • Haiti : • Risk for HIV transmission among HIV discordant couples : • 7 and 3 times higher respectively when HIV- partner had GUD and syphilis.Deschamps MM et al: Ann Int Med 1986 125:324-330 • Jamaica: Extensive research and development of a comprehensive program that led to the decrease in STIs. Figueroa JP. West Indian Med. J. 2001,sup 4:15-22

  21. Behavioral/Cultural Cofactors of Heterosexual Transmission • Dysfunctional gender relations • Macho concept • Multiple partners; early sex • Bisexuality vs MSM • Early initiation of sexual activity (De Moya A in Ramirez et al (eds) Masculine Identities in the Caribbean) • FCSWS: COIN developed a model program for prevention of STIs in The Dominican Republic • IVDU (Puerto-Rico) as many are heterosexual • Condom use: • Consistent condom use is protective. Deschamps MM et al: Ann Int Med 1986 125:324-330 • Difficulty of interpretation of self-reported condom use Weir S et al (DeMoya A, Gomez B, Guerrero E) Int. J STD&AIDS. 1998;9:223-226 • Policy Environmental in support of condom use is essential for consistent condom use among FCSWs. Kerrigan et al (Moreno L, Rosario S). AIDS. 2003,17:415-423

  22. Other Cofactors of Heterosexual Transmission • Poverty and STIs in rural Haiti: • Fawzi et al. Int.J STD/AIDS. 2003,14:848-853 • Migration: (Bateyes, DR) • Outside the country: Brewer T, Hasbun J, Butler de Lister M, Constanzo J AIDS.1998,12:1879-1887 • In-country, from rural to urban areas: Farmer P. Culture, poverty and the dynamics of HIV transmission in rural Haiti. In Culture and sexual risl. Newark, NJ, 1995:3-28 • Tourism: issues linked to STIs and how they can be addressed. Forsythe S, Hasbun J, Butler de Lister M. Health Policy and Plan. 1998,13:3:277-286

  23. HIV MTCT • Puerto-Rico: PACTG 076: 1st study showing efficacy of ZDV to reduce MTCT. Connor E et al (Jimenez E) N Engl J Med 1994;331:1173-1180 • Barbados: ZDV- treated mother-infant pairs to 5.5% St John A et al. Ped Inf. Dis. 2003:22;(5);422-25 • Dominican Republic: > 80 MTCT centers . Perez E et al. JAIDS.2003,34:5:506-511 • Obstetrical factors associated with MTCT: Prolonged rupture of the membranes, maternal drug use, low birth weight, pre-term birth > HIV MTCT. Landesman SH et al (Zorilla C, Garcia P) NEnglJMed 1996 334:1617-23 • Non-Obstetrical factors associated with MTCT and the specific role of viral load. Garcia P et al (Zorilla C). NEnglJMed 1999 341;394-402; Sperling R et al (Jimenez E) NEnglJMed 1996:335:22:1621-28 - Urgent to provide the best therapy to the mother to decrease viral load and reduce MTCT • Family Planning Integration aimed primarily at HIV+ women: Dechamps et al. Int Pro Div 2000,719-723

  24. Perinatal HIV Transmission Rate In Puerto-Rico (1990-2002) Source: Ryan White Title IV Program, OCASET, 2002

  25. Survival curves of HIV-infected Haitian children born to HIV+ mothers in Miami and Port-au-Prince Jean, SS et al Ped Infect Dis J 1999,18: 1; 58-63.

  26. Pediatric HIV/AIDS • Association of disease progression with • Viral load in perinatally infected children.Shearer W et al (Diaz C) N Engl J Med 1997,336:1337-42 Suggests early therapy may be indicated in such cases. • Other associated infections (Staphylococal infections, M. tuberculosis (Haiti) • Disease progression with early onset (< 3 months) of clinical S/S (lymphadenoptahy, hepato, splenomegaly) and early positive culture (1st week of life). Diaz C et al JAIDS 1998:18:3; 221-228 • Natural history of pediatric HIV/AIDS in Jamaica: TB most common OI. Pierre R et al. West Ind Med Jour. 2003,52(suppl) 1-7

  27. Natural History of HIV Infection in the Caribbean (1) Deschamps MM et al. AIDS. 2000, 14:2515-2521 (2) Cleghorn F. et al JAIDS. 2004, in press

  28. Universal Access to Antiretroviral Therapy • Experience of Puerto-Rico • Bitherapy (ZDV + 3 TC) is better than either alone Eron J et al (Santana J) N Engl J Med 1995,333:25:1662-1669 • Experience of French Territories • Care Cabie et al • Resistance to ARV (Dos Santos) • Bahamas: • 56% reduction in adult AIDS death ; 89% reduction in AIDS mortality among children • Bermuda: • 83 % reduction of AIDS cases from 1995 to 2001 • Barbados: • 42% reduction in AIDS mortality in 5 years • Dutch Caribbean: Marked reduction in mortality

  29. Farmer P et al Lancet .2001,358:404-09

  30. Antiretroviral Therapy and Survival Kaplan Meier Estimate of survival in HIV infected adults treated with antiretroviral therapy (ART) by Gheskio compared to survival of historical controls diagnosed with AIDS before ART was available.

  31. HIV vaccine sites

  32. National HIV Seroprevalence in Haiti (1993-2003) Pregnant women at 1st antenatal visit MSPP/IHE/CDC/GHESKIO

  33. Summary • Considerable amount of research in the Caribbean with much public health impact. • Success stories that show that the epidemic can be controlled • The information must be shared and a common data base developed • Major contribution can continue to be made in both prevention (HIV vaccine) and care IF we are united against HIV/AIDS; our diversity should be our strength not our weakness • Eleanor Roosevelt : “ The future belongs to those who believe in the beauty of their dreams”: A world without AIDS

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