CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men

Susan M. Thomas, Doris B. Tse, D. Scott Ketner, Gemma Rochford, Daniel A. Meyer, David D. Zade, Perry N. Halkitis, Arthur Nádas, William Borkowsky, Michael Marmor

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Δ32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1α (CCL3), MIP-1β (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Δ32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Δ32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.

Original languageEnglish (US)
Pages (from-to)1879-1883
Number of pages5
JournalAIDS
Volume20
Issue number14
DOIs
StatePublished - Sep 2006

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Sexual Behavior
HIV
HIV-1
HIV Infections
Monocytes
Alleles
T-Lymphocytes
Chemokine CCL5
Genetic Polymorphisms
Linear Models
Flow Cytometry
Cross-Sectional Studies
Regression Analysis
Polymerase Chain Reaction
Mutation
Infection

Keywords

  • CCR5 expression
  • CCR5-Δ32
  • CCR5-59029
  • CD4+ monocytes
  • CD4+ T cells
  • HIV-1 seronegative

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Thomas, S. M., Tse, D. B., Ketner, D. S., Rochford, G., Meyer, D. A., Zade, D. D., ... Marmor, M. (2006). CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men. AIDS, 20(14), 1879-1883. https://doi.org/10.1097/01.aids.0000244207.49123.ff

CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men. / Thomas, Susan M.; Tse, Doris B.; Ketner, D. Scott; Rochford, Gemma; Meyer, Daniel A.; Zade, David D.; Halkitis, Perry N.; Nádas, Arthur; Borkowsky, William; Marmor, Michael.

In: AIDS, Vol. 20, No. 14, 09.2006, p. 1879-1883.

Research output: Contribution to journalArticle

Thomas, SM, Tse, DB, Ketner, DS, Rochford, G, Meyer, DA, Zade, DD, Halkitis, PN, Nádas, A, Borkowsky, W & Marmor, M 2006, 'CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men', AIDS, vol. 20, no. 14, pp. 1879-1883. https://doi.org/10.1097/01.aids.0000244207.49123.ff
Thomas, Susan M. ; Tse, Doris B. ; Ketner, D. Scott ; Rochford, Gemma ; Meyer, Daniel A. ; Zade, David D. ; Halkitis, Perry N. ; Nádas, Arthur ; Borkowsky, William ; Marmor, Michael. / CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men. In: AIDS. 2006 ; Vol. 20, No. 14. pp. 1879-1883.
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abstract = "OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Δ32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1α (CCL3), MIP-1β (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Δ32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Δ32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.",
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AU - Thomas, Susan M.

AU - Tse, Doris B.

AU - Ketner, D. Scott

AU - Rochford, Gemma

AU - Meyer, Daniel A.

AU - Zade, David D.

AU - Halkitis, Perry N.

AU - Nádas, Arthur

AU - Borkowsky, William

AU - Marmor, Michael

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N2 - OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Δ32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1α (CCL3), MIP-1β (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Δ32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Δ32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.

AB - OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Δ32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1α (CCL3), MIP-1β (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Δ32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Δ32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.

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