CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam

Lien X. Truong, Tram T. Luong, Daniel Scott-Algara, Pierre Versmisse, Annie David, Danielle Perez-Bercoff, Ngai V. Nguyen, Hung K. Tran, Cuc T. Cao, Arnaud Fontanet, Jean Yves Follézou, Ioannis Theodorou, Françoise Barré-Sinoussi, Gianfranco Pancino*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

Abstract

Objective: To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals. Design: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1425-1434
Number of pages10
JournalAIDS
Volume17
Issue number10
DOIs
Publication statusPublished - 4 Jul 2003
Externally publishedYes

Keywords

  • Cell susceptibility to infection
  • Exposed uninfected
  • HIV-1
  • Intravascular drug users
  • Restriction of viral replication

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