Hemophilia and nonprogressing human immunodeficiency virus type 1 infection.
Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.
Vicenzi
E
E
DIBIT, Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Bagnarelli
P
P
Santagostino
E
E
Ghezzi
S
S
Alfano
M
M
Sinnone
M S
MS
Fabio
G
G
Turchetto
L
L
Moretti
G
G
Lazzarin
A
A
Mantovani
A
A
Mannucci
P M
PM
Clementi
M
M
Gringeri
A
A
Poli
G
G
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D018925:Chemokines / Q000096:biosynthesis; D015331:Cohort Studies; D004279:DNA, Viral / Q000302:isolation & purification; D018450:Disease Progression; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006467:Hemophilia A / Q000150:complications*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010949:Plasma / Q000821:virology; D011533:Proviruses / Q000302:isolation & purification; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D017741:Survivors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014766:Viremia / Q000821:virology; D014776:Virus Cultivation; D014779:Virus Replication
D018925:Chemokines; D004279:DNA, Viral; D012367:RNA, Viral