Anaemia has been linked with mortality in HIV infection. The mechanism of anaemia in the era of contemporary antiretroviral therapy is not understood. The aim of this study was to describe the association between anaemia and markers of immune activation and inflammation in a cohort of HIV-infected adults on stable antiretroviral therapy.
Methods
We performed a cross-sectional study of HIV-infected adults on antiretroviral therapy with HIV-1 RNA<1,000 copies/ml. Soluble and cellular markers of inflammation and immune activation were measured. Relationships between haemoglobin levels, anaemia (haemoglobin <13 g/dl for men and <12 g/dl for women) and mild anaemia (haemoglobin <14 g/dl for men and <13 g/dl for women) and these markers were explored using multivariable linear regression.
Results
Among the 147 participants, median age was 46 years, 78% were men, 68% were African American and 29% were Caucasian. Median body mass index (BMI) was 26.7 kg/m2, nadir and current CD4+ T-cell counts were 179 and 613 cells/mm3, respectively, and 78% had HIV-1 RNA<50 copies/ml (range 20–600 copies/ml). Median (IQR) haemoglobin was 14.3 (13.1– 15.1) g/dl; 14% were anaemic and 33% had at least mild anaemia. In multivariable analyses, mild anaemia was independently associated with female sex, older age, shorter duration of antiretroviral therapy, lower white blood cell count, higher platelet count, higher sCD14 and a greater number of CD14dimCD16+ cells or ‘patrolling’ monocytes, which remained significant after further adjusting for race and BMI.
Conclusions
Having haemoglobin <14 g/dl for men and <13 g/dl for women was independently associated with monocyte activation (sCD14 and CD14dimCD16+ cells) in HIV-infected adults on stable antiretroviral therapy.
References
1.
HuangS.S., BarbourJ.D., DeeksS.G.Reversal of human immunodeficiency virus type 1-associated hematosuppression by effective antiretroviral therapy.Clin Infect Dis2000; 30: 504–510.
2.
BelperioP.S., RhewD.C.Prevalence and outcomes of anemia in individuals with human immunodeficiency virus: a systematic review of the literature.Am J Med2004; 116Suppl 7A: 27S–43S.
3.
BorgesÁ.H., WeitzJ.I., CollinsG.Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.AIDS2014; 28: 1791–1796.
4.
McDermidJ.M., van der LoeffM.F., JayeA.Mortality in HIV infection is independently predicted by host iron status and SLC11A1 and HP genotypes, with new evidence of a gene-nutrient interaction.Am J Clin Nutr2009; 90: 225–233.
5.
MelekhinV.V., ShepherdB.E., StinnetteS.E., RebeiroP.F., TurnerM.M., SterlingT.R.Hemoglobin may contribute to sex differences in mortality among HIV-infected persons in care.PLoS ONE2012; 7: e44999.
6.
TheurlI., MattleV., SeifertM., MarianiM., MarthC., WeissG.Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease.Blood2006; 107: 4142–4148.
7.
SasuB.J., LiH., RoseM.J., ArvedsonT.L., DoellgastG., MolineuxG.Serum hepcidin but not prohepcidin may be an effective marker for anemia of inflammation (AI).Blood Cells Mol Dis2010; 45: 238–245.
8.
MinchellaP.A., ArmitageA.E., DarboeB.Elevated hepcidin concentrations at HIV diagnosis are associated with increased mortality.7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. 30 June–3 July 2013, Kuala Lumpur, Malaysia. Abstract MOLBPE08.
9.
WeissG., GoodnoughL.T.Anemia of chronic disease.N Engl J Med2005; 352: 1011–1023.
10.
FuchsD., ZangerleR., Artner-DworzakE.Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection.Eur J Haematol1993; 50: 90–94.
11.
SarclettiM., QuirchmairG., WeissG., FuchsD., ZangerleR.Increase of haemoglobin levels by anti-retroviral therapy is associated with a decrease in immune activation.Eur J Haematol2003; 70: 17–25.
12.
FunderburgN.T., JiangY., DebanneS.M.Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.Clin Infect Dis2014; 58: 588–595.
13.
FunderburgN.T., ZidarD.A., ShiveC.Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.Blood2012; 120: 4599–4608.
14.
CrosJ., CagnardN., WoollardK.Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors.Immunity2010; 33: 375–386.
15.
InkerL.A., SchmidC.H., TighiouartH.Estimating glomerular filtration rate from serum creatinine and cystatin C.N Engl J Med2012; 367: 20–29.
16.
RegidorD.L., DetelsR., BreenE.C.Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte activation and inflammation.AIDS2011; 25: 303–314.
17.
RossA.C., RizkN., O'RiordanM.A.Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy.Clin Infect Dis2009; 49: 1119–1127.
18.
BhatiaV., ChaudhuriA., TomarR., DhindsaS., GhanimH., DandonaP.Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes.Diabetes Care2006; 29: 2289–2294.
19.
KengneA.P., CzernichowS., HamerM., BattyG.D., StamatakisE.Anaemia, haemoglobin level and cause-specific mortality in people with and without diabetes.PLoS ONE2012; 7: e41875.
20.
MassonC.Rheumatoid anemia.Joint Bone Spine2011; 78: 131–137.
21.
HøivikM.L., ReinischW., CvancarovaM., MoumB.Anaemia in inflammatory bowel disease: a population-based 10-year follow-up.Aliment Pharmacol Ther2014; 39: 69–76.
22.
BurdoT.H., LoJ., AbbaraS.Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients.J Infect Dis2011; 204: 1227–1236.
23.
LongeneckerC.T., JiangY., OrringerC.E.Soluble CD14 is independently associated with coronary calcification and extent of subclinical vascular disease in treated HIV infection.AIDS2014; 28: 969–977.
24.
KelesidisT., KendallM.A., YangO.O., HodisH.N., CurrierJ.S.Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection.J Infect Dis2012; 206: 1558–1567.
25.
SubramanianS., TawakolA., BurdoT.H.Arterial inflammation in patients with HIV.JAMA2012; 308: 379–386.
26.
BurdoT.H., WeiffenbachA., WoodsS.P., LetendreS., EllisR.J., WilliamsK.C.Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection.AIDS2013; 27: 1387–1395.
27.
SandlerN.G., WandH., RoqueA.Plasma levels of soluble CD14 independently predict mortality in HIV infection.J Infect Dis2011; 203: 780–790.
