Skip Navigation LinksHome > November 1, 2006 - Volume 43 - Issue 3 > The Immunological Response to Highly Active Antiretroviral T...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000234088.64655.45
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*

Free Access
Article Outline
Collapse Box

Author Information

*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).

Figure 1
Figure 1
Image Tools

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

Back to Top | Article Outline

REFERENCES

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.

Cited By:

This article has been cited 5 time(s).

Antibiotiques
CCR5 antagonists and HIV-1 infection: Bases and consequences of this therapeutic approach
Psomas, KC; Corbeau, P; Reynes, J
Antibiotiques, 12(1): 27-41.
10.1016/j.antib.2010.01.006
CrossRef
Medecine Et Maladies Infectieuses
CCR5-antagonists: Contribution of a new antiretroviral class to the management of HIV infection
Poizot-Martin, I
Medecine Et Maladies Infectieuses, 40(5): 245-255.
10.1016/j.medmal.2010.03.007
CrossRef
Plos One
CCL3L1-CCR5 Genotype Improves the Assessment of AIDS Risk in HIV-1-Infected Individuals
Kulkarni, H; Agan, BK; Marconi, VC; O'Connell, RJ; Camargo, JF; He, WJ; Delmar, J; Phelps, KR; Crawford, G; Clark, RA; Dolan, MJ; Ahuja, SK
Plos One, 3(9): -.
ARTN e3165
CrossRef
Journal of Clinical Virology
Control of HIV 1 RNA load after HAART interruption: Relationship with CCR5 co-receptor density and proviral DNA load in HIV infected patients
Soriano-Sarabia, N; Vallejo, A; Fernandez, G; Genebat, M; Gutierrez, S; Munoz-Fernandez, MA; Leal, M
Journal of Clinical Virology, 40(1): 64-67.
10.1016/j.jcv.2007.06.010
CrossRef
AIDS
CCR5 antagonism in HIV infection: ways, effects, and side effects
Corbeau, P; Reynes, J
AIDS, 23(15): 1931-1943.
10.1097/QAD.0b013e32832e71cd
PDF (1362) | CrossRef
Back to Top | Article Outline

© 2006 Lippincott Williams & Wilkins, Inc.

Login