CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam.
OBJECTIVE
To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals.


METHODS
We examined in-vitro cell susceptibility to HIV-1 infection in highly exposed Vietnamese intravascular drug users (IDU) who, despite a history of more than 10 years of drug use and a high prevalence of other blood-borne viral infections, remain apparently HIV uninfected.


METHODS
Forty-five exposed uninfected IDU and 50 blood donors were included in the study. Peripheral blood mononuclear cells (PBMC) or CD4 cell susceptibilities to HIV infection were evaluated using three HIV-1 isolates with different tropisms. Polymerase chain reaction analysis of HIV-1-DNA replication intermediates was used to characterize the restriction of HIV-1 replication in CD4 cells. Homologous CD8 cells were mixed with infected CD4 cells to evaluate their role in virus suppression.


RESULTS
We observed a relative resistance to PBMC infection with HIV-1 in 21 out of 45 exposed uninfected IDU, but only in five out of 50 unexposed controls (P < 0.001). PBMC resistance was related either to an inhibition of HIV-1 replication in CD4 cells or to CD8 cell-mediated viral suppression. HIV-1 replication in CD4 cells was restricted at the early stages of the viral cycle.


CONCLUSIONS
Reduced PBMC susceptibility to HIV-1 infection was associated with resistance to infection in exposed uninfected IDU. Distinct mechanisms are involved in in-vitro resistance and may contribute to the apparent protection from HIV-1 transmission in this systemically exposed population.
Truong
Lien X
LX
Institut Pasteur and bHôpital Binh-Trieu, Ho Chi Minh City, Vietnam.
Luong
Tram T
TT
Scott-Algara
Daniel
D
Versmisse
Pierre
P
David
Annie
A
Perez-Bercoff
Danielle
D
Nguyen
Ngai V
NV
Tran
Hung K
HK
Cao
Cuc T
CT
Fontanet
Arnaud
A
Follézou
Jean-Yves
JY
Theodorou
Ioannis
I
Barré-Sinoussi
Françoise
F
Pancino
Gianfranco
G
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D018925:Chemokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D019713:Receptors, CCR5 / Q000378:metabolism; D015819:Substance Abuse, Intravenous; D014744:Vietnam; D014779:Virus Replication
D018925:Chemokines; D019713:Receptors, CCR5