Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5–14, reproductive age adults 18–49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5–11 <10.5 g/dl, 12–14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44–4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92–3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management.
Get full access to this article
View all access options for this article.
References
1.
BenoistB, McLeanE, EgllI, and CogswellM: Worldwide Prevalence of Anaemia 1993–2005: WHO Global Database on Anaemia (de BenoistB, ed.). World Health Organization, Geneva, Switzerland, 2008.
2.
VolberdingPA, LevineAM, DieterichD, MildvanD, MitsuyasuR, and SaagM: Anemia in HIV infection: Clinical impact and evidence-based management strategies. Clin Infect Dis, 2004; 38(10):1454–1463.
3.
CalisJCJ, van HensbroekMB, de HaanRJ, MoonsP, BrabinBJ, and BatesI: HIV-associated anemia in children: A systematic review from a global perspective. AIDS, 2008; 22(10):1099.
4.
VolberdingP: Consensus statement: Anemia in HIV infection—current trends, treatment options, and practice strategies. Clin Ther, 2000; 22(9):1004–1020.
5.
MocroftA, KirkO, BartonSE, et al.: Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. AIDS, 1999; 13(8):943–950.
6.
WisaksanaR, SumantriR, IndratiAR, et al.: Anemia and iron homeostasis in a cohort of HIV-infected patients in Indonesia. BMC Infect Dis, 2011; 11(1):213.
7.
O'BrienME, KupkaR, MsamangaGI, SaathoffE, HunterDJ, and FawziWW: 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(2):219–225.
8.
JohannessenA, NamanE, GundersenSG, and BruunJN: Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania. BMC Infect Dis, 2011; 11(1):190.
9.
MooreRD and ForneyD: Anemia in HIV-infected patients receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr, 2002; 29(1):54.
10.
MildvanD, CreaghT, and LeitzG: Prevalence of anemia and correlation with biomarkers and specific antiretroviral regimens in 9690 human-immunodeficiency-virus-infected patients: Findings of the Anemia Prevalence Study. Curr Med Res Opin, 2007; 23(2):343–355.
11.
OwireduW, QuayeLN A, and Addai-MensahO: Prevalence of anaemia and immunological markers among Ghanaian HAART-naive HIV-patients and those on HAART. Afr Health Sci, 2011; 11(1):2–15.
12.
GigantiMJ, LimbadaM, MwangoA, et al.: 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(1):120–123.
13.
MugyenyiP, WalkerA, HakimJ, et al.: Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): A randomised non-inferiority trial. Lancet, 2010; 375(9709):123–131.
14.
KekitiinwaA, CookA, NathooK, et al.: Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): A 5-year open-label randomised factorial trial. Lancet, 2013; 381(9875):1391–1403.
15.
WHO: Antiretroviral Therapy of HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach. World Health Organization, Geneva, 2006.
16.
DART: Twenty-four-week safety and tolerability of nevirapine vs. abacavir in combination with zidovudine/lamivudine as first-line antiretroviral therapy: A randomized double-blind trial (NORA). Trop Med Int Health, 2008; 13(1):6–16.
17.
WHO: Iron Deficiency Anaemia: Assessment, Prevention and Control: A Guide for Programme Managers. World Health Organization, Geneva, 2001.
18.
MasaisaF, GahutuJB, MukiibiJ, DelangheJ, and PhilippeJ: Anemia in human immunodeficiency virus-infected and uninfected women in Rwanda. Am J Trop Med Hyg, 2011; 84(3):456–460.
NeginJ and CummingRG: HIV infection in older adults in sub-Saharan Africa: Extrapolating prevalence from existing data. Bull World Health Organ, 2010; 88(11):847–853.
21.
HighKP, Brennan-IngM, CliffordDB, et al.: HIV and aging: State of knowledge and areas of critical need for research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group. J Acquir Immune Defic Syndr, 2012; 60:S1–S18.
22.
VanasseGJ and BerlinerN: Anemia in elderly patients: An emerging problem for the 21st century. Hematology Am Soc Hematol Educ Program, 2010; 2010(1):271–275.
23.
de PeeS and SembaRD: Role of nutrition in HIV infection: Review of evidence for more effective programming in resource-limited settings. Food Nutr Bull, 2010; 31(Suppl 4):313S–344S.
24.
EleyBS, SiveAA, ShuttleworthM, and HusseyGD: A prospective, cross-sectional study of anaemia and peripheral iron status in antiretroviral naive, HIV-1 infected children in Cape Town, South Africa. BMC Infect Dis, 2002; 2(1):3.
25.
TotinD, NdugwaC, MmiroF, PerryRT, JacksonJB, and SembaRD: Iron deficiency anemia is highly prevalent among human immunodeficiency virus-infected and uninfected infants in Uganda. J Nutr, 2002; 132(3):423–429.
26.
ShetA, ArumugamK, RajagopalanN, et al.: The prevalence and etiology of anemia among HIV-infected children in India. Eur J Pediatr, 2012; 171(3):531–540.
27.
ObirikorangC and YeboahFA: Blood haemoglobin measurement as a predictive indicator for the progression of HIV/AIDS in resource-limited setting. J Biomed Sci, 2009; 16:102.
28.
SsaliF, StöhrW, MunderiP, et al.: 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(6):741–749.
29.
WalkerAS, PrendergastAJ, MugyenyiP, et al.: Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis, 2012; 55(12):1707–1718.
30.
AnudeC, EzeE, OnyegbutulemH, et al.: 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(1):113.
31.
LabhardtND, LejoneT, SetokoMl, et al.: 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(10):e47937.
32.
SullivanPS, HansonDL, and BrooksJT: Impact on hemoglobin of starting combination antiretroviral therapy with or without zidovudine in anemic HIV-infected patients. J Acquir Immune Defic Syndr, 2008; 48(2):163–168.
33.
MgogweJ, SemvuaH, MsangiR, MataroC, KajegukaD, and ChilongolaJ: The evolution of haematological and biochemical indices in HIV patients during a six-month treatment period. Afr Health Sci, 2012; 12(1):2–7.
34.
WHO: Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. World Health Organization, Geneva, 2013.
35.
MunyazesaE, EmileI, MutimuraE, et al.: Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: A cross-sectional study. BMJ Open, 2012; 2(6).
36.
SembaRD, ShahN, KleinRS, MayerKH, SchumanP, and VlahovD: Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and uninfected women. Clin Infect Dis, 2002; 34(2):260–266.
37.
LevineAM, BerhaneK, Masri-LavineL, et al.: Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's Interagency HIV Study. J Acquir Immune Defic Syndr, 2001; 26(1):28–35.
38.
MelekhinVV, ShepherdBE, StinnetteSE, RebeiroPF, TurnerMM, and SterlingTR: Hemoglobin may contribute to sex differences in mortality among HIV-infected persons in care. PLoS One, 2012; 7(9):e44999.
39.
BalarajanY, RamakrishnanU, OzaltinE, ShankarAH, and SubramanianS: Anaemia in low-income and middle-income countries. Lancet, 2012; 378(9809):2123–2135.
40.
MehtaS, SpiegelmanD, AboudS, et al.: Lipid-soluble vitamins A, D, and E in HIV-infected pregnant women in Tanzania. Eur J Clin Nutr, 2010; 64(8):808–817.
41.
KupkaR, MsamangaGI, MugusiF, PetraroP, HunterDJ, and FawziWW: Iron status is an important cause of anemia in HIV-infected Tanzanian women but is not related to accelerated HIV disease progression. J Nutr, 2007; 137(10):2317–2323.
42.
BaltazaryG, AkarroR, and MussaA: Some factors associated with non-adherence to antiretroviral therapy (ART) in people living with HIV/AIDS (PLHA) in Tanzania: A case study of Dar es Salaam region. East Afr J Public Health, 2011; 8(4):237.
43.
FawziWW, MsamangaGI, KupkaR, et al.: Multivitamin supplementation improves hematologic status in HIV-infected women and their children in Tanzania. Am J Clin Nutr, 2007; 85(5):1335–1343.
44.
GeboKA: Epidemiology of HIV and response to antiretroviral therapy in the middle aged and elderly. Aging Health, 2008; 4(6):615–627.
45.
BattegayM, FehrJ, FlückigerU, and ElziL: Antiretroviral therapy of late presenters with advanced HIV disease. J Antimicrob Chemother, 2008; 62(1):41–44.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
