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Volume 6 Supplement 3

AIDS Vaccine 2009

P07-11 LB. Impact of highly active antiretroviral therapy on cell-free and cell-associated HIV-1 in cervicovaginal secretions and blood

Background

Heterosexual contact is a major route for HIV-1 transmission and cervicovaginal secretions (CVS) contain both cell-associated and cell-free virus. Nevertheless, these different forms of HIV-1 and their involvement in sexual transmission have been poorly characterized.

Methods

CVS and blood were sampled in 80 HIV-1 infected women. Cells phenotype was analyzed by flow cytometry and levels of spontaneous HIV-1-antigen secreting CD4+ T cells were evaluated by ELIspot assay. Cell-free virus was quantified in CVS and paired plasma while cell-associated virus was assayed in cell-culture supernatants.

Results

Cell-free HIV-1 RNA was frequently detected in CVS from patients viremic for HIV RNA in plasma but was unusual in aviremic patients (75% versus 16%, and mean = 5921 copies/ml versus 2696 copies/ml, respectively, P < 0.001). Levels of HIV-1 RNA were positively correlated in CVS and plasma (ρ = 0.7, P < 0.001). CVS contains low T lymphocytes quantities (mean = 120 CD4+ cells/ml and 133 CD8+ cells/ml) and CVS-derived CD4+ T cells are mostly memory and activated lymphocytes (CD45RA-, HLA-DR+, CD38+, CD69+). Those cells were strikingly different from blood CD4+ T cells with a phenotype exhibiting a mucosal profile with higher expression of CD103 combined with lower expression of CCR7. Cell-associated HIV-1 RNA was detectable in only 3/51 CVS including 2 from viremic patients, whereas 28/51 plasma cell-culture supernatants were positive. Levels of cell-associated HIV-1 RNA were higher in blood samples of viremic individuals than in undetectable subjects (P = 0.01).

Conclusion

Therapy reduces viral production and shedding in genital and blood compartments but cell-free HIV-1 remains detectable in some aviremic patients. Level of genital cell-free HIV-1 RNA is influenced by systemic viral replication in contrast to genital cell-associated HIV-1, which may be influenced by local factors. The little amount of CD4+ T cells observed in CVS suggests that sexual transmission occurs independently of HIV-1-infected cells located in CVS but involve intraepithelial cell-associated HIV-1 or cell-free virus.

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Correspondence to P Rubbo.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Rubbo, P., Tuaillon, E., Nagot, N. et al. P07-11 LB. Impact of highly active antiretroviral therapy on cell-free and cell-associated HIV-1 in cervicovaginal secretions and blood. Retrovirology 6, P397 (2009). https://doi.org/10.1186/1742-4690-6-S3-P397

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Keywords

  • Sexual Transmission
  • ELIspot Assay
  • Infected Woman
  • Blood Compartment
  • Heterosexual Contact