JAIDS Journal of Acquired Immune Deficiency Syndromes:
Letters to the Editor
The Immunological Response to Highly Active Antiretroviral Therapy Is Linked to CD4+ T-Cell Surface CCR5 Density
Vincent, Thierry MD, PhD*; Portalès, Pierre MD*; Baillat, Vincent MD†; Eden, Aurélia MD†; Clot, Jacques MD*; Reynes, Jacques MD†; Corbeau, Pierre MD, PhD*
*Laboratoire d'Immunologie Hôpital Saint Eloi Montpellier, France, †Service des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac Montpellier, France
To the Editor:
There is interindividual variability in the clinical progression of HIV-1-infected individuals on highly active antiretroviral therapy (HAART) that is linked to their virologic response.1 One of the major host factors that determines the intensity of virus replication in vitro2 and in vivo3 is the mean number of CCR5 coreceptors at the surface of the CD4+ target cells. Because we have previously shown that the virologic response to HAART correlates with this CD4+ T-cell surface CCR5 density,4 in this study, we addressed whether CD4+ T-cell surface CCR5 density, which varies widely among all individuals but is stable over time in asymptomatic HIV-1-infected individuals, particularly on nonactivated human leukocyte antigen-D-related (HLA-DR)-negative CD4+ T cells,3 might influence the immunologic response to HAART.
To test this hypothesis, we determined by quantitative flow cytometry3 CCR5 density on peripheral blood HLA-DR− CD4+ T cells of 37 chronically infected subjects (7 women and 30 men with a pretherapeutic CD4 T-cell count ranging from 7 to 343 cells/μL and a pretherapeutic HIV-1 RNA plasma level ranging from 3200 to 3000,000 copies/mL) who had received HAART (30% nucleoside analogues only, 8% nucleoside analogues and nonnucleoside reverse transcriptase inhibitors, 54% nucleoside analogues and protease inhibitors, and 8% nucleoside and nonnucleoside reverse transcriptase inhibitors as well as protease inhibitors initially), including at least 2 drugs to which they had not previously been exposed, with a decent initial virologic response (<1000 HIV RNA copies/mL at month 12). We observed an inverse correlation (r = −0.41, P = 0.01) between CCR5 expression and the increase in CD4+ T-cell count after 48 months of treatment (Fig. 1).
Our data show that the individual level of CCR5 expression is linked not only to natural HIV disease progression but to progression on therapy. Thus, CD4+ T-cell surface CCR5 density might be predictive of immunologic evolution while on treatment. Finally, our observation strengthens the idea that lowering CCR5 expression is a highly desirable therapeutic goal and that CCR5 antagonists should potentiate classic anti-HIV drugs.
Thierry Vincent, MD, PhD*
Pierre Portalès, MD*
Vincent Baillat, MD†
Aurélia Eden, MD†
Jacques Clot, MD*
Jacques Reynes, MD†
Pierre Corbeau, MD, PhD*
*Laboratoire d'Immunologie Hôpital Saint Eloi Montpellier, France
†Service des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac Montpellier, France
1. Lederberger B, Egger M, Opravil M, et al. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet. 1999;353:863-868.
2. Lin Y-L, Mettling C, Portales P, et al. Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection. Proc Natl Acad Sci USA. 2002;99:15590-15595.
3. Reynes J, Portales P, Segondy M, et al. CD4+ T cell surface CCR5 density as a determining factor of viral load in HIV-1-infected individuals. J Infect Dis. 2000;181:927-932.
4. Gervaix A, Nicolas J, Portales P, et al. Response to treatment and disease progression linked to CD4+ T cell surface CCR5 density in HIV-1 vertical infection. J Infect Dis. 2002;185:1055-1061.
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© 2006 Lippincott Williams & Wilkins, Inc.