Resolution of anaemia in a cohort of HIV-infected patients with a high prevalence and incidence of tuberculosis receiving antiretroviral therapy in South Africa

BMC Infectious Diseases

Stephen D Lawn³  Linda-Gail Bekker²  Ankur Gupta-Wright³  Frank G Cobelens¹  Robin Wood²  Andrew D Kerkhoff² 

[1]KNCV Tuberculosis Foundation, The Hague, the Netherlands

[2]The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

[3]Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

关键词: Antiretroviral;    Haemoglobin;    Anaemia;    Africa;    Tuberculosis;    HIV;   

Others  :  1090222
DOI  :  10.1186/s12879-014-0702-1

 received in 2014-09-05, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

Anaemia is frequently associated with both HIV-infection and HIV-related tuberculosis (TB) in antiretroviral therapy (ART)-naïve patients in sub-Saharan Africa and is strongly associated with poor prognosis. However, the effect of ART on the resolution of anaemia in patient cohorts with a high prevalence and incidence of tuberculosis is incompletely defined and the impact of TB episodes on haemoglobin recovery has not previously been reported. We therefore examined these issues using data from a well-characterised cohort of patients initiating ART in South Africa.

Methods

Prospectively collected clinical and haematological data were retrospectively analysed from patients receiving ART in a South African township ART service. TB diagnoses and time-updated haemoglobin concentrations, CD4 counts and HIV viral loads were recorded. Anaemia severity was classified according to WHO criteria. Multivariable logistic regression analysis was used to determine factors independently associated with anaemia after 12 months of ART.

Results

Of 1,140 patients with baseline haemoglobin levels, 814 were alive in care and had repeat values available after 12 months of ART. The majority of patients were female (73%), the median CD4 count was 104 cells/uL and 30.5% had a TB diagnosis in the first year of ART. At baseline, anaemia (any severity) was present in 574 (70.5%) patients and was moderate/severe in 346 (42.5%). After 12 months of ART, 218 (26.8%) patients had anaemia of any severity and just 67 (8.2%) patients had moderate/severe anaemia. Independent predictors of anaemia after 12 months of ART included greater severity of anaemia at baseline, time-updated erythrocyte microcytosis and receipt of an AZT-containing regimen. In contrast, prevalent and/or incident TB, gender and baseline and time-updated CD4 cell count and viral load measurements were not independent predictors.

Conclusions

Although anaemia was very common among ART-naive patients, the anaemia resolved during the first year of ART in a large majority of patients regardless of TB status without routine use of additional interventions. However, approximately one-quarter of patients remained anaemic after one year of ART and may require additional investigations and/or interventions.

【 授权许可】

   
2014 Kerkhoff et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Johannessen A, Naman E, Gundersen SG, Bruun JN: Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania. BMC Infect Dis 2011, 11:190. BioMed Central Full Text
• [2]Jaganath D, Walker AS, Ssali F, Musiime V, Kiweewa F, Kityo C, Salata R, Mugyenyi P: DART Trial, ARROW Trial: HIV-associated anemia after 96 weeks on therapy: determinants across age ranges in Uganda and Zimbabwe. AIDS Res Hum Retroviruses 2014, 30:523-530.
• [3]Omoregie R, Omokaro EU, Palmer O, Ogefere HO, Egbeobauwaye A, Adeghe JE, Osakue SI, Ihemeje V: Prevalence of anaemia among HIV-infected patients in Benin City, Nigeria. Tanzan J Health Res 2009, 11:1-4.
• [4]O'Brien ME, Kupka R, Msamanga GI, Saathoff E, Hunter DJ, Fawzi WW: Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania. J Acquir Immune Defic Syndr 2005, 40:219-225.
• [5]Daka D, Lelissa D, Amsalu A: Prevalence of anaemia before and after the initiation of antiretroviral therapy at ART centre of Hawassa University Referral Hospital, Hawassa, South Ethiopia. Scholarly-Journalscom 2013, 3:1-6.
• [6]Saag MS, Bowers P, Leitz GJ, Levine AM, Community HIV: Anemia Management Protocol Sites (CHAMPS) Study Group: Once-weekly epoetin alfa improves quality of life and increases hemoglobin in anemic HIV+ patients. AIDS Res Hum Retroviruses 2004, 20:1037-1045.
• [7]Grossman HA, Goon B, Bowers P, Leitz G: 010 Study Group: Once-weekly epoetin alfa dosing is as effective as three times-weekly dosing in increasing hemoglobin levels and is associated with improved quality of life in anemic HIV-infected patients. J Acquir Immune Defic Syndr 2003, 34:368-378.
• [8]Revicki DA, Brown RE, Henry DH, McNeill MV, Rios A, Watson T: Recombinant human erythropoietin and health-related quality of life of AIDS patients with anemia. J Acquir Immune Defic Syndr 1994, 7:474-484.
• [9]Mocroft A, Kirk O, Barton SE, Dietrich M, Proenca R, Colebunders R, Pradier C, d'Arminio Monforte A, Ledergerber B, Lundgren JD: Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group. AIDS 1999, 13:943-950.
• [10]Obirikorang C, Yeboah FA: Blood haemoglobin measurement as a predictive indicator for the progression of HIV/AIDS in resource-limited setting. Journal of Biomedical Science 2009, 16:102. BioMed Central Full Text
• [11]Meriki HD, Tufon KA, Afegenwi MH, Nyindem BA, Atanga PN, Anong DN, Cho-Ngwa F, Nkuo-Akenji T: Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon. Infect Dis Poverty 2014, 3:5. BioMed Central Full Text
• [12]Labhardt ND, Lejone T, Setoko M, Poka M, Ehmer J, Pfeiffer K, Kiuvu PZ, Lynen L: A clinical prediction score in addition to WHO criteria for anti-retroviral treatment failure in resource-limited settings - experience from Lesotho. PLoS ONE 2012, 7:e47937.
• [13]Anude CJ, Eze E, Onyegbutulem HC, Charurat M, Etiebet M-A, Ajayi S, Dakum P, Akinwande O, Beyrer C, Abimiku A, Blattner W: Immuno-virologic outcomes and immuno-virologic discordance among adults alive and on anti-retroviral therapy at 12 months in Nigeria. BMC Infect Dis 2013, 13:113. BioMed Central Full Text
• [14]Harris RJ, Sterne JA, Abgrall S, Dabis F, Reiss P, Saag M, Phillips AN, Chene G, Gill JM, Justice AC: Prognostic importance of anaemia in HIV type-1-infected patients starting antiretroviral therapy: collaborative analysis of prospective cohort studies. Antivir Ther 2007, 13:959-967.
• [15]Johannessen A, Naman E, Ngowi BJ, Sandvik L, Matee MI, Aglen HE, Gundersen SG, Bruun JN: Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infect Dis 2008, 8:52. BioMed Central Full Text
• [16]Russell EC, Charalambous S, Pemba L, Churchyard GJ, Grant AD, Fielding K: Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study. BMC Public Health 2010, 10:433. BioMed Central Full Text
• [17]Moore RD, Keruly JC, Chaisson RE: Anemia and survival in HIV infection. J Acquir Immune Defic Syndr 1998, 19:29-33.
• [18]Weiss G, Goodnough LT: Anemia of chronic disease. N Engl J Med 2005, 352:1011-1023.
• [19]Chelucci C, Hassan HJ, Locardi C, Bulgarini D, Pelosi E, Mariani G, Testa U, Federico M, Valtieri M, Peschle C: In vitro human immunodeficiency virus-1 infection of purified hematopoietic progenitors in single-cell culture. Blood 1995, 85:1181-1187.
• [20]Molina JM, Scadden DT, Sakaguchi M: Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus. Blood 1990, 76:2476-2482.
• [21]Shen H, Cheng T, Preffer FI, Dombkowski D, Tomasson MH, Golan DE, Yang O, Hofmann W, Sodroski JG, Luster AD, Scadden DT: Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite coreceptor expression. Journal of Virology 1999, 73:728-737.
• [22]Redd AD, Avalos A, Essex M: Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa. Blood 2007, 110:3143-3149.
• [23]Neal TF, Holland HK, Baum CM: CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. Blood 1995, 86:1749-1756.
• [24]Kerkhoff AD, Wood R, Vogt M, Lawn SD: Predictive value of anemia for tuberculosis in HIV-infected patients in Sub-Saharan Africa: an indication for routine microbiological investigation using new rapid assays. J Acquir Immune Defic Syndr 2014, 66:33-40.
• [25]Lewis DK, Whitty CJM, Walsh AL, Epino H, Broek NRVD, Letsky EA, Munthali C, Mukiibi JM, Boeree MJ: Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence. Trans R Soc Trop Med Hyg 2005, 99:561-567.
• [26]van Lettow M, West CE, van der Meer JWM, Wieringa FT, Semba RD: Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi. Eur J Clin Nutr 2005, 59:526-532.
• [27]Shah S, Whalen C, Kotler DP, Mayanja H, Namale A, Melikian G, Mugerwa R, Semba RD: Severity of human immunodeficiency virus infection is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary tuberculosis infection in Uganda. J Nutr 2001, 131:2843-2847.
• [28]Singh KJ, Ahluwalia G, Sharma SK, Saxena R, Chaudhary VP, Anant M: Significance of haematological manifestations in patients with tuberculosis. J Assoc Physicians India 2001, 49:788–790–4.
• [29]Lee SW, Kang YA, Yoon YS, Um S-W, Lee SM, Yoo C-G, Kim YW, Han SK, Shim Y-S, Yim J-J: The prevalence and evolution of anemia associated with tuberculosis. J Korean Med Sci 2006, 21:1028-1032.
• [30]Isanaka S, Mugusi F, Urassa W, Willett WC, Bosch RJ, Villamor E, Spiegelman D, Duggan C, Fawzi WW: Iron deficiency and anemia predict mortality in patients with tuberculosis. J Nutr 2012, 142:350-357.
• [31]Marshall JB: Tuberculosis of the gastrointestinal tract and peritoneum. Am J Gastroenterol 1993, 88:989-999.
• [32]Hungund BR, Sangolli SS, Bannur HB, Malur PR, Pilli GS, Chavan RY, Dafale SR, Joshi AV: Blood and bone marrow findings in tuberculosis in adults-A cross sectional study. Al Ameen J Med Sci 2012, 5:362–366.
• [33]Olaniyi JA, Aken'Ova YA: Bone marrow findings in patients with pulmonary tuberculosis. Afr J Med Med Sci 2003, 32:155-157.
• [34]Singh KJ, Ahulwalia G, Sharma SK, Saxena R, Chaudhary VP, Anant M: Significance of haematological manifestations in patients with tuberculosis. J Assoc Physicians India 2001, 49:790-794.
• [35]Semba RD, Shah N, Klein RS, Mayer KH, Schuman P, Gardner LI, Vlahov D: HER (Human Immunodeficiency Virus Epidemiology Research) Study Group: Highly active antiretroviral therapy associated with improved anemia among HIV-infected women. AIDS Patient Care STDS 2001, 15:473-480.
• [36]Moore RD, Forney D: Anemia in HIV-infected patients receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2002, 29:54-57.
• [37]Sullivan PS, Hanson DL, Brooks JT: Impact on hemoglobin of starting combination antiretroviral therapy with or without zidovudine in anemic HIV-infected patients. J Acquir Immune Defic Syndr 2008, 48:163-168.
• [38]Berhane K, Karim R, Cohen MH, Masri-Lavine L, Young M, Anastos K, Augenbraun M, Watts DH, Levine AM: Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study. J Acquir Immune Defic Syndr 2004, 37:1245-1252.
• [39]Semba RD, Shah N, Vlahov D: Improvement of anemia among HIV-infected injection drug users receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001, 26:315-319.
• [40]Moh R, Danel C, Sorho S, Sauvageot D, Anzian A, Minga A, Gomis OB, Konga C, Inwoley A, Gabillard D: Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with co-trimoxazole in Côte d’Ivoire. Antivir Ther 2005, 10:615-624.
• [41]Kiragga AN, Castelnuovo B, Nakanjako D, Manabe YC: Baseline severe anaemia should not preclude use of zidovudine in antiretroviral-eligible patients in resource-limited settings. J Int AIDS Soc 2010, 13:42. BioMed Central Full Text
• [42]Takuva S, Maskew M, Brennan AT, Sanne I, MacPhail AP, Fox MP: Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen. Journal of Tropical Medicine 2013, 2013:1-6.
• [43]Forna F, Moore D, Mermin J, Brooks JT, Were W, Buchacz K, Campbell JD, Downing R, Borkowf CB, Weidle PJ: Hematologic changes associated with Zidovudine following single-drug substitution from stavudine in a home-based AIDS care program in rural Uganda. J Int Assoc Physicians AIDS Care (Chic) 2009, 8:128-138.
• [44]Adane A, Desta K, Bezabih A, Gashaye A, Kassa D: HIV-associated anaemia before and after initiation of antiretroviral therapy at Art Centre of Minilik II Hospital, Addis Ababa, Ethiopia. Ethiop Med J 2012, 50:13-21.
• [45]Parrish DD, Blevins M, Megazzini KM, Shepherd BE, Mohammed MY, Wester CW, Vermund SH, Aliyu MH: Haemoglobin recovery among HIV-1 infected patients on zidovudine-based antiretroviral therapy and other regimens in north-central Nigeria. Int J STD AIDS 2014, 5:355–359.
• [46]Ssali F, Stöhr W, Munderi P, Reid A, Walker AS, Gibb DM, Mugyenyi P, Kityo C, Grosskurth H, Hakim J, Byakwaga H, Katabira E, Darbyshire JH, Gilks CF: DART Trial Team: Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial. Antivir Ther 2006, 11:741-749.
• [47]Lawn SD, Myer L, Orrell C, Bekker L-G, Wood R: Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 2005, 19:2141-2148.
• [48]Lawn SD, Myer L, Bekker L-G, Wood R: Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. AIDS 2006, 20:1605-1612.
• [49]WHO: Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. World Health Organization, Geneva; 2013.
• [50]Lawn SD, Obeng J, Acheampong JW, Griffin GE: Resolution of the acute-phase response in West African patients receiving treatment for pulmonary tuberculosis. Int J Tuberc Lung Dis 2000, 4:340-344.
• [51]Lee JH, Chang JH: Changes of plasma interleukin-1 receptor antagonist, interleukin-8 and other serologic markers during chemotherapy in patients with active pulmonary tuberculosis. Korean J Intern Med 2003, 18:138-145.
• [52]Friedland JS, Hartley JC, Hartley CG, Shattock RJ, Griffin GE: Cytokine secretion in vivo and ex vivo following chemotherapy of Mycobacterium tuberculosis infection. Trans R Soc Trop Med Hyg 1996, 90:199-203.
• [53]WHO: Nutritional Anaemias: Report of a WHO Scientific Group [Meeting Held in Geneva From 13 to 17 March 1967]. World Health Organization, Geneva; 1968.
• [54]Giganti MJ, Limbada M, Mwango A, Moyo C, Mulenga LB, Guffey MB, Mulenga PL, Bolton-Moore C, Stringer JSA, Chi BH: Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr 2012, 61:120-123.
• [55]Hoffmann CJ, Fielding KL, Charalambous S, Sulkowski MS, Innes C, Thio CL, Chaisson RE, Churchyard GJ, Grant AD: Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events. AIDS 2008, 22:67-74.
• [56]WHO: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. World Health Organization, Geneva; 2011.
• [57]Sarcletti M, Quirchmair G, Weiss G, Fuchs D, Zangerle R: Increase of haemoglobin levels by anti‐retroviral therapy is associated with a decrease in immune activation. Eur J Haematol 2003, 70:17-25.
• [58]Claster S: Biology of anemia, differential diagnosis, and treatment options in human immunodeficiency virus infection. J INFECT DIS 2002, 185(Suppl 2):S105-S109.
• [59]Fitzsimons EJ, Brock JH: The anaemia of chronic disease. BMJ 2001, 322:811-812.
• [60]Massey AC: Microcytic anemia. Differential diagnosis and management of iron deficiency anemia. Med Clin North Am 1992, 76:549-566.
• [61]Morley JE, Thomas DR, Wilson M-MG: Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 2006, 83:735-743.
• [62]May M, Boulle A, Phiri S, Messou E, Myer L, Wood R, Keiser O, Sterne JA, Dabis F, Egger M: Africa FISAAW: Prognosis of patients with HIV-1 infection startingantiretroviral therapy in sub-Saharan Africa: a collaborativeanalysis of scale-up programmes. The Lancet 2010, 376:449-457.
• [63]Lawn SD, Kranzer K, Edwards DJ, Mcnally M, Bekker L-G, Wood R: Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS 2010, 24:1323-1328.
• [64]Lawn SD, Kerkhoff AD, Vogt M, Wood R: Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect Dis 2012, 12:201-209.