Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection.
OBJECTIVE
To determine the impact of Plasmodium falciparum malaria coinfection and its treatment on cellular reservoirs of viral replication in HIV-1-infected persons and to relate this to changes in systemic immune activation.


METHODS
Plasma samples were obtained from HIV-1-infected individuals (n = 10) at diagnosis of acute malaria, 4 weeks after parasite clearance and from HIV-infected aparasitemic controls (n = 10). Immunomagnetic HIV-1 capture analysis was used to determine the cellular origin of cell-free virus particles present in all 30 plasma samples and indices of immune activation were measured using enzyme-linked immunosorbent assays.


RESULTS
Compared with controls, the detectable proportion of HIV-1 particles derived from CD14 macrophages and CD26 lymphocytes was increased in persons with acute malaria coinfection and correlated with markedly increased plasma concentrations of both proinflammatory cytokines and soluble markers of macrophage and lymphocyte activation. Parasite clearance following treatment with antimalarial drugs resulted in decreased detection of HIV-1 particles derived from the CD14 macrophage cell subset and correlated with a marked diminution in systemic immune activation.


CONCLUSIONS
Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation.
HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Georgia, USA..
Tracy L
TL
Pisell
Irving F
IF
Hoffman
Charles S
CS
Jere
Sarah B
SB
Ballard
Malcolm E
ME
Molyneux
Salvatore T
ST
Butera
Stephen D
SD
Lawn
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000469:parasitology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006684:HLA-DR Antigens / Q000032:analysis; D006790:Host-Parasite Interactions; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000276:immunology / Q000469:parasitology* / Q000821:virology*; D008288:Malaria / Q000150:complications* / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D012367:RNA, Viral; D018819:Dipeptidyl Peptidase 4