1921
Volume 74, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Access to antiretroviral (ARV) drugs is improving in sub-Saharan Africa but still constrained by several clinical and logistical obstacles. There is a need to develop affordable markers to guide initiation of treatment. We present a prospective cohort study of 779 patients participating in a TB prophylaxis trial. We performed separate analyses for anergic and nonanergic subjects. Prognostic factors for anergic and nonanergic subjects differed between groups. Individuals with anergy and constitutional symptoms were at the highest risk of death. Incident tuberculosis and CD4 < 200 cells/μL at enrollment were the strongest risk factors for death. HIV disease is associated with substantial morbidity and mortality in this population. The burden caused by tuberculosis is particularly high. Anergy is a strong and independent predictor of death. World Health Organization criteria to start ARV may be strengthened with the addition of DTH testing, an inexpensive and readily available tool in sub-Saharan Africa.

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2006-01-01
2017-11-25
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References

  1. Serwadda D, Mugerwa RD, Sewankambo NK, Lwegaba A, Carswell JW, Kirya GB, Bayley AC, Downing RG, Tedder RS, Clayden SA, 1985. Slim disease: a new disease in Uganda and its association with HTLV-III infection. Lancet 2 : 849–852.
  2. World Health Organization (WHO). 2003. AIDS Epidemic Update. Geneva: WHO.
  3. Mbulaiteye SM, Mahe C, Whitworth JA, Ruberantwari A, Nakiyingi JS, Ojwiya A, Kamali A, 2002. Declining HIV-1 incidence and associated prevalence over 10 years in a rural population in south-west Uganda: a cohort study. Lancet 360 : 41–46.
  4. World Health Organization (WHO). 2003. Scaling up Antiretroviral Therapy in Resource-Limited Settings (Draft). Geneva: WHO.
  5. Montaner JS, Le TN, Le N, Craib KJ, Schechter MT, 1992. Application of the World Health Organization system for HIV infection in a cohort of homosexual men in developing a prognostically meaningful staging system. AIDS 6 : 719–724.
  6. Aylward RB, Vlahov D, Munoz A, Rapiti E, 1994. Validation of the proposal World Health Organization staging system for disease and infection in a cohort of intravenous drug users. AIDS 8 : 1129–1133.
  7. Lifson AR, Allen S, Wolf W, Serufilira A, Kantarama G, Lindan CP, Hudes ES, Nsengumuremyi F, Taelman H, Batungwanayo J, 1995. Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications. Ann Intern Med 122 : 262–270.
  8. Malamba SS, Morgan D, Clayton T, Mayanja B, Okongo M, Whitworth J, 1999. The prognostic value of the World Health Organization staging system for HIV infection and disease in rural Uganda. AIDS 13 : 2555–2562.
  9. Kassa E, Rinke de Wit TF, Hailu E, Girma M, Messele T, Mariam HG, Yohannes S, Jurriaans S, Yeneneh H, Coutinho RA, Fontanet AL, 1999. Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers. AIDS 13 : 381–389.
  10. Post FA, Badri M, Wood R, Maartens G, 2001. AIDS in Africa—Survival according to AIDS-defining illness. S Afr Med J 91 : 583–586.
  11. Morgan D, Mahe C, Mayanja B, Whitworth JAG, 2002. Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: Prospective cohort study. BMJ 324 : 193–197.
  12. Schreibman T, Friedland G, 2004. Use of Total Lymphocyte Count for Monitoring Response to Antiretroviral Therapy. Clin Infect Dis 38 : 257–262.
  13. Morpeth S, Shao H, Kisenge P, Bartlett J, Moylan C, Naggie S, Caram B, Sam N, Itemba D, Ole-Nguyaine S, Crump J, Thielman N, 2005. Evaluating simple low-cost predictors of CD4 count <200 for scale-up of antiretroviral therapy in developing countries [Poster 638b]. CROI, Boston, Feb. 22–25.
  14. Duvignac J, Anglaret X, Kpozehouen A, Toure S, Inwoley A, 2005. Thiebaut and ANRS 1203 Study Group. Factors associated with changes in CD4+ T Cells in HAART-naïve Sub-Saharan African HIV-infected adults [Poster 622]. CROI, Boston, Feb. 22–25.
  15. Arnaud J, Loretxu P, Alexandra C, Jacques I, Didakus O, Limangeni M, Gloria K, Elisabeth S, Chris B, Serge B, Gaelle F, Nathan F, Ferradini L. Clinical and virological outcomes of patients on HAART in a large-scale simplified treatment program in a rural district of Malawi [Poster 625b]. CROI, Boston, Feb. 22–25.
  16. Caiaffa WT, Graham NM, Galai N, Rizzo RT, Nelson KE, Vlahov D, 1995. Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection. Arch Intern Med 155 : 2111–2117.
  17. Chin DP, Osmond D, Page-Shafer K, Glassroth J, Rosen MJ, Reichman LB, Kvale PA, Wallace JM, Poole WK, Hopewell PC, 1996. Reliability of anergy skin testing in persons with HIV infection. The pulmonary Complication of HIV Infection Study Group. Am J Respir Crit Care Med 153 : 1982–1984.
  18. Johnson JL, Nyole S, Okwera A, Whalen CC, Nsubuga P, Pekovic V, Huebner R, Wallis RS, Mugyenyi PN, Mugerwa RD, Ellner JJ, 1998. Instability of Tuberculin and Candida Skin Test Reactivity in HIV-infected Ugandans. Am J Respir Crit Care Med 158 : 1790–1796.
  19. Blatt SP, Hendrix CW, Butzin CA, Freeman TM, Ward WW, Hensley RE, Melcher GP, Donovan DJ, Boswell RN, 1993. Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients. Ann Intern Med 119 : 177–184.
  20. Birx DL, Brundage J, Larson K, Engler R, Smith L, Squire E, Carpenter G, Sullivan M, Rhoads J, Oster C, 1993. The prognostic utility of delayed-type hypersensitivity skin testing in the evaluation of HIV-infected patients. J Acquir Immune Defic Syndr 6 : 1248–1257.
  21. Gordin FM, Hartigan PM, Klimas NG, Zolla-Pazner SB, Simberkoff MS, Hamilton JD, 1994. Delayed-type hypersensitivity skin tests are an independent predictor of HIV disease progression. Department of Veterans Affairs Cooperative Study. J Infect Dis 169 : 893–897.
  22. Karlsson A, Moberg L, Bratt G, Halvarsson M, von Krogh G, Morfeldt L, Sandstrom E, 1996. An eleven year follow-up of delayed-type hypersensitivity testing for the identification of HIV-1 infected patients at increased risk of developing AIDS. Scand J Infect Dis 28 : 125–130.
  23. Brown AE, Markowitz L, Nitayaphan S, Morgan P, Sukwit S, Chinaworapong S, Leelasupasri S, Birx D, 2000. DTH responsiveness of HIV-infected Thai adults. J Med Assoc Thai 83 : 633–639.
  24. Whalen CC, Johnson JL, Okwera A, Hom DL, Huebner R, Mugyenyi P, Mugerwa RD, Ellner JJ, 1997. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with HIV. N Engl J Med 337 : 801–808.
  25. Kleinbaum DG, 1996. Survival analysis. Extension of the Cox Proportional Hazards Models for Time-Dependent Variables. New York: Springer-Verlag, 211–253.
  26. Redfield RR, Wright DC, Tramont EC, 1986. The Walter Reed staging classification for HTLV-III/LAV infection. N Engl J Med 314 : 131–132.
  27. Centers for Disease Control (CDC), 1997. Anergy skin testing and preventive therapy for HIV-infected persons: revised recommendations. MMWR 46 : 1–10.
  28. Separ Guidelines (Spain), 2002. Guidelines for tuberculosis prevention. Arch Bronconeumol 38 : 441–451.
  29. Rieder HL, Zellweger JP, Raviglione MC, Keizer ST, Migliori GB, 1994. Tuberculosis control in Europe and international migration. Eur Respir J 7 : 1545–1553.
  30. 2000. Control and prevention of tuberculosis in the United Kingdom: code of practice 2000. Thorax 55 : 887–901.
  31. Clerici M, Shearer GM, 1993. A TH1 (arrow right) TH2 switch is a critical step in the etiology of HIV infection. Immunol Today 14 : 107–111.
  32. Delgado JC, Tsai EY, Thim S, Baena A, Boussiotis VA, Reynes JM, Sath S, Grosjean P, Yunis EJ, Goldfeld AE, 2002. Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia. PNAS 99 : 7576–7581.
  33. Hertoghe T, Wajja A, Ntambi L, Okwera A, Aziz MA, Hirsch C, Johnson J, Toossi Z, Mugerwa R, Mugyenyi P, Colebunders R, Ellner J, Vanham G, 2000. T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB). Clin Exp Immunol 122 : 350–357.
  34. Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C, 2003. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 163 : 1009–1021.
  35. Elliott AM, Hayes RJ, Halwiindi B, Luo N, Tembo G, Pobee JO, Nunn PP, McAdam KP, 1995. The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia. Trans R Soc Trop Med Hyg 89 : 78–82.
  36. Whalen C, Horsburgh CR, Hom D, Lahart C, Simberkoff M, Ellner J, 1995. Accelerated course of human immunodeficiency virus infection after tuberculosis. J Respir Crit Care Med 151 : 129–135.
  37. Perneger TV, Sudre P, Lundgren JD, Hirschel B, 1995. Does the onset of tuberculosis in AIDS predict shorter survival? Results of a cohort study in 17 European countries over 13 years. BMJ 311 : 468–471.
  38. Tacconelli E, Tumbarello M, Ardito F, Cauda R, 1997. Tuberculosis significantly reduces the survival of patients with AIDS. Int J Tuberc Lung Dis 1 : 582–584.
  39. Leroy V, Salmi LR, Dupon M, Sentilhes A, Texier-Maugein J, Dequae L, Dabis F, Salamon R, 1997. Progression of human immunodeficiency virus infection in patients with tuberculosis disease: a cohort study in Bordeaux, France, 1988–1994. Am J Epidemiol 145 : 293–300.
  40. Whalen CC, Nsubuga P, Okwera A, Johnson JL, Hom DL, Michael NL, Mugerwa RD, Ellner JJ, 2000. The impact of tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 14 : 1219–1228.
  41. Badri M, Ehrlich R, Wood R, Pulerwitz T, Maartens G, 2001. Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area. Int J Tuberc Lung Dis 5 : 225–232.
  42. Toossi Z, 2003. Virological and immunological impact of tuberculosis on human immunodeficiency virus type 1 disease. J Infect Dis 188 : 1146–1155.
  43. Wilkinson D, Squire SB, Garner P, 1998. Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomized placebo-controlled trials. BMJ 317 : 625–629.
  44. Sawert H, Girardi E, Antonucci G, Raviglione MC, Viale P, Ippolito G, 1998. Preventive therapy for tuberculosis in HIV-infected persons. Arch Inter Med 158 : 2112–2121.
  45. Currie CSM, Williams BG, Cheng RCH, Dye C, 2003. Tuberculosis epidemics driven by HIV: is prevention better than cure? AIDS 17 : 2501–2508.
  46. Smith RA, Ellenberg JH, Douglas SD, Henry RL, Peralta L, Wilson CM, 2000. The prevalence of anergy in human immunodeficiency virus-infected adolescents and the association of delayed-type hypersensitivity with subject characteristics. J Adolesc Health 27 : 384–390.
  47. Trauger RJ, Giermakowska WK, Ferre F, Duffy PC, Wallace MR, Lewis DE, Beecham HJ, Burnett KG, Jensen FC, Carlo DJ, 1993. Cell-mediated immunity to HIV-1 in Walter Reed stages 1–6 individuals: correlation with virus burden. Immunology 78 : 611–615.
  48. Lederman MM, Connick E, Landay A, Kuritzkes DR, Spritzler J, St. Clair M, Kotzin BL, Fox L, Chiozzi MH, Leonard JM, Rousseau F, Wade M, Roe JD, Martinez A, Kessler H, 1998. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis 178 : 70–79.
  49. Lederman MM, 2001. Immune restoration and CD4+ T-cell function with antiretroviral strategies. AIDS 15 (Suppl 2): S11–S15.
  50. Weiss L, Ancuta P, Girard PM, Bouhlal H, Roux A, Cavaillon NH, Kazatchkine MD, 1999. Restoration of normal interleukin-2 production by CD4+ T cells of human immunodeficiency virus-infected patients after 9 months of highly active antiretroviral therapy. J Infect Dis 180 : 1057–1063.
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  • Received : 06 Jan 2005
  • Accepted : 08 Jun 2005

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