Abnormalities of erythropoiesis during HIV-1 disease: a longitudinal analysis.
BACKGROUND
Impaired erythropoiesis is a key abnormality described in untreated HIV-1 disease. Most of the available data on HIV-associated hematopoietic abnormalities were obtained using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter (and intra)-individual variability in the number of cultured precursors. Aim of this study was to assess the erythropoietic capability of purified CD34+ progenitors through a longitudinal analysis of burst-forming units-erythroid (BFU-E) growth before and after antiretroviral therapy (ART).


METHODS
Twelve HIV-infected individuals were studied before and after ART; 31 HIV-uninfected individuals were enrolled as controls. CD34+ progenitors were purified from peripheral blood by immunomagnetic sorting and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor, interleukin-3, and erythropoietin. Serum levels of iron, transferrin, transferrin saturation index, soluble transferrin receptor, ferritin, and erythropoietin were also evaluated.


RESULTS
Baseline BFU-E levels were increased in untreated HIV-infected individuals when compared with controls but declined significantly after successful ART. In contrast, serum levels of erythropoietin and soluble transferrin receptor increased significantly after ART.


CONCLUSIONS
These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective erythropoiesis and accumulation of erythroid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of BFU-E levels.
Costantini
Andrea
A
Dipartimento di Scienze Mediche e Chirurgiche, Università Politecnica delle Marche, Ancona, Italy. a.costantini@univpm.it
Giuliodoro
Simona
S
Butini
Luca
L
Silvestri
Guido
G
Leoni
Pietro
P
Montroni
Maria
M
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D015497:HIV-1; D006402:Hematologic Diseases / Q000821:virology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019089:Stem Cell Factor / Q000494:pharmacology
D019380:Anti-HIV Agents; D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor