Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen
Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART. 1. Background Anemia has been shown to be the most frequent hematological abnormality in HIV-infected patients globally [1, 2]. Even among those initiating antiretroviral therapy (ART), anemia has been demonstrated to be a strong risk factor for disease progression and subsequent death [1–5] independent of CD4 count and viral load. In a large European cohort study, the presence of severe anemia at ART initiation was associated with a 13-fold increased risk of death [3]. In sub-Saharan Africa, which has the largest burden of HIV in the world, anemia is common as patients are more likely to be malnourished, have advanced immunosuppression, and have higher rates of comorbidities (especially tuberculosis and malaria) than those in high-income countries [6, 7]. Despite the public health importance of anemia, prospective data from sub-Saharan Africa on its impact are limited. Recent reports suggest that hemoglobin levels improve with ART [2, 3, 8]; however, few studies have documented the evolution of hemoglobin levels among patients on ART in resource-limited settings, and whether the effects on hemoglobin levels vary by ART regimen. Given the number of patients on ART in this region, understanding the role of anemia in HIV treatment is critical to developing strategies
References
[1]
P. S. Sullivan, D. L. Hanson, S. Y. Chu, J. L. Jones, and J. W. Ward, “Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project,” Blood, vol. 91, no. 1, pp. 301–308, 1998.
[2]
R. D. Moore and D. Forney, “Anemia in HIV-infected patients receiving highly active antiretroviral therapy,” Journal of Acquired Immune Deficiency Syndromes, vol. 29, no. 1, pp. 54–57, 2002.
[3]
A. Mocroft, O. Kirk, S. E. Barton et al., “Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe,” AIDS, vol. 13, no. 8, pp. 943–950, 1999.
[4]
J. D. Lundgren, A. Mocroft, J. M. Gatell, et al., “A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA Study,” Journal of Infectious Diseases, vol. 185, no. 1, pp. 178–187, 2002.
[5]
R. D. Moore, J. C. Keruly, and R. E. Chaisson, “Anemia and survival in HIV infection,” Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, vol. 19, no. 1, pp. 29–33, 1998.
[6]
World Health Organization, Worldwide Prevalence of Anemia 1993–2005: WHO Global Database on Anemia, WHO, Geneva, Switzerland, 2008.
[7]
R. D. Semba and G. E. Gray, “Pathogenesis of anemia during human immunodeficiency virus infection,” Journal of Investigative Medicine, vol. 49, no. 3, pp. 225–239, 2001.
[8]
A. Johannessen, E. Naman, S. G. Gundersen, and J. N. Bruun, “Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania,” BMC Infectious Diseases, vol. 11, article 190, 2011.
[9]
J. Camacho, F. Poveda, A. F. Zamorano, M. E. Valencia, J. J. Vazquez, and F. Arnalich, “Serum erythropoietin levels in anaemic patients with advanced human immunodeficiency virus infection,” British Journal of Haematology, vol. 82, no. 3, pp. 608–614, 1992.
[10]
G. Moyle, W. Sawyer, M. Law, J. Amin, and A. Hill, “Changes in hematologic parameters and efficacy of thymidine analogue based, highly active antiretroviral therapy: a meta-analysis of six prospective, randomized, comparative studies,” Clinical Therapeutics, vol. 26, no. 1, pp. 92–97, 2004.
[11]
M. A. Jacobson, L. Peiperl, P. A. Volberding, D. Porteous, P. T. C. Y. Toy, and D. Feigal, “Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome,” Transfusion, vol. 30, no. 2, pp. 133–137, 1990.
[12]
N. Frickhofen, J. L. Abkowitz, M. Safford et al., “Persistent B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS,” Annals of Internal Medicine, vol. 113, no. 12, pp. 926–933, 1990.
[13]
D. W. Northfelt, A. Mayer, L. D. Kaplan et al., “The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection,” Journal of Acquired Immune Deficiency Syndromes, vol. 4, no. 7, pp. 659–666, 1991.
[14]
M. H. McGinniss, A. M. Macher, A. H. Rook, and H. J. Alter, “Red cell autoantibodies in patients with acquired immune deficiency syndrome,” Transfusion, vol. 26, no. 5, pp. 405–409, 1986.
[15]
A. N. Kiragga, B. Castelnuovo, D. Nakanjako, and Y. C. Manabe, “Baseline severe anaemia should not preclude use of zidovudine in antiretroviral-eligible patients in resource-limited settings,” Journal of the International AIDS Society, vol. 13, no. 1, article 42, 2010.
[16]
F. Ssali, W. St？hr, P. Munderi et al., “Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial,” Antiviral Therapy, vol. 11, no. 6, pp. 741–749, 2006.
[17]
M. P. Fox, M. Maskew, A. P. Macphail, et al., “Cohort Profile: The Themba Lethu Clinical Cohort, Johannesburg, South Africa,” International Journal of Epidemiology, vol. 42, no. 2, pp. 430–439, 2013.
[18]
National Department of Health, Republic of South Africa, National Antiretroviral Treatment Guidelines, Jacana, 2004.
[19]
Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, National Institutes of Health Division of AIDS, 2004.
[20]
C. J. Hoffmann, K. L. Fielding, S. Charalambous et al., “Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events,” AIDS, vol. 22, no. 1, pp. 67–74, 2008.
[21]
R. D. Semba, N. Shah, R. S. Klein, K. H. Maye, P. Schuman, and D. Vlahov, “Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and -uninfected women,” Clinical Infectious Diseases, vol. 34, no. 2, pp. 260–266, 2002.
[22]
T. S. Wills, J. P. Nadler, C. Somboonwit et al., “Anemia prevalence and associated risk factors in a single-center ambulatory HIV clinical cohort,” AIDS Reader, vol. 14, no. 6, pp. 305–310, 2004.
[23]
J. Zhou, A. Jaquet, E. Bissagnene et al., “Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America,” Journal of the International AIDS Society, vol. 15, no. 1, article 5, 2012.
[24]
S. Takuva, G. Louwagie, K. Zuma, and V. Okello, “Durability of first line antiretroviral therapy: reasons and predictive factors for modifications in a Swaziland Cohort,” Journal of Antivirals and Antiretrovirals, vol. 4, no. 1, pp. 14–20, 2012.
[25]
R. Subbaraman, S. K. Chaguturu, K. H. Mayer, T. P. Flanigan, and N. Kumarasamy, “Adverse effects of highly active antiretroviral therapy in developing countries,” Clinical Infectious Diseases, vol. 45, no. 8, pp. 1093–1101, 2007.
[26]
C. Laurent, A. Bourgeois, E. Mpoudi-Ngolé et al., “Tolerability and effectiveness of first-line regimens combining nevirapine and lamivudine plus zidovudine or stavudine in Cameroon,” AIDS Research and Human Retroviruses, vol. 24, supplement 3, pp. 393–399, 2008.
[27]
D. Coetzee, K. Hildebrand, A. Boulle et al., “Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa,” AIDS, vol. 18, no. 6, pp. 887–895, 2004.
