Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents

Jianming Tang, Craig M. Wilson, Shreelatha Meleth, Angela Myracle, Elena Lobashevsky, Mark J. Mulligan, Steven D. Douglas, Bette Korber, Sten H. Vermund, Richard A. Kaslow, L. Friedman, L. Pall, D. Maturo, A. Pasquale, D. Futterman, D. Monte, M. Alovera-DeBellis, N. Hoffman, S. Jackson, D. Schwarz & 71 others B. Rudy, M. Tanney, A. Feldman, M. Belzer, D. Tucker, C. Hosmer, K. Chung, S. E. Abdalian, L. Green, C. McKendall, L. Wenthold, L. J. D'Angelo, C. Trexler, C. Townsend-Akpan, R. Hagler, J. A. Morrissy, L. Peralta, C. Ryder, S. Miller, S. Calianno, L. Henry-Reid, R. Camacho, M. Sturdevant, A. Howell, J. E. Johnson, A. Puga, D. Cruz, P. McLendon, M. Sawyer, J. Tigner, A. Simmonds, P. Flynn, K. Lett, J. Dewey, S. Discenza, L. Levin, M. Geiger, P. Stanford, F. Briggs, J. Birnbaum, M. Ramnarine, V. Guarino, C. Holland, A. B. Moscicki, D. A. Murphy, P. Crowley-Nowick, C. Partlow, S. J. Durako, J. H. Ellenberg, B. Hobbs, A. Bennett, M. Camarca, K. Clingan, J. Houser, V. Junankar, O. Leytush, L. Muenz, Y. Ma, R. Mitchell, T. Myint, P. Ohan, L. Paolinelli, M. Rakheja, M. Sarr, A. Soloviov, A. Rogers, A. Willoughby, K. Davenny, V. Smeriglio, E. Matzen, B. Vitiello

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-l-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1 -seropositive adolescents (ages 13-18 years; 75% females; 71% African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6-12-month interval when no antiretroviral therapy was taken. Results: HLA-B* 57 alone was a strong predictor of VL (P <0.0001), but composite genetic profiles found in over 50% of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (<1000 copies/ml) and CD4 T cell counts (> 450 × 106 cells/I) consistently had more positive (+1 to +2) than negative (-1 to -4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells <450 × 106 cells/I) or the remainder (n = 134) of the cohort (overall P <0.0001). Conclusion: A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.

Original languageEnglish (US)
Pages (from-to)2275-2284
Number of pages10
JournalAIDS
Volume16
Issue number17
DOIs
StatePublished - Nov 22 2002
Externally publishedYes

Fingerprint

Chemokines
HIV Infections
HIV-1
Viral Load
HIV
Viremia
Genetic Markers
African Americans
Haplotypes
Alleles
T-Lymphocytes
Therapeutics

Keywords

  • Adolescents
  • CCR5
  • Genetics
  • HIV-1
  • HLA
  • Prognosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tang, J., Wilson, C. M., Meleth, S., Myracle, A., Lobashevsky, E., Mulligan, M. J., ... Vitiello, B. (2002). Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. AIDS, 16(17), 2275-2284. https://doi.org/10.1097/00002030-200211220-00007

Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. / Tang, Jianming; Wilson, Craig M.; Meleth, Shreelatha; Myracle, Angela; Lobashevsky, Elena; Mulligan, Mark J.; Douglas, Steven D.; Korber, Bette; Vermund, Sten H.; Kaslow, Richard A.; Friedman, L.; Pall, L.; Maturo, D.; Pasquale, A.; Futterman, D.; Monte, D.; Alovera-DeBellis, M.; Hoffman, N.; Jackson, S.; Schwarz, D.; Rudy, B.; Tanney, M.; Feldman, A.; Belzer, M.; Tucker, D.; Hosmer, C.; Chung, K.; Abdalian, S. E.; Green, L.; McKendall, C.; Wenthold, L.; D'Angelo, L. J.; Trexler, C.; Townsend-Akpan, C.; Hagler, R.; Morrissy, J. A.; Peralta, L.; Ryder, C.; Miller, S.; Calianno, S.; Henry-Reid, L.; Camacho, R.; Sturdevant, M.; Howell, A.; Johnson, J. E.; Puga, A.; Cruz, D.; McLendon, P.; Sawyer, M.; Tigner, J.; Simmonds, A.; Flynn, P.; Lett, K.; Dewey, J.; Discenza, S.; Levin, L.; Geiger, M.; Stanford, P.; Briggs, F.; Birnbaum, J.; Ramnarine, M.; Guarino, V.; Holland, C.; Moscicki, A. B.; Murphy, D. A.; Crowley-Nowick, P.; Partlow, C.; Durako, S. J.; Ellenberg, J. H.; Hobbs, B.; Bennett, A.; Camarca, M.; Clingan, K.; Houser, J.; Junankar, V.; Leytush, O.; Muenz, L.; Ma, Y.; Mitchell, R.; Myint, T.; Ohan, P.; Paolinelli, L.; Rakheja, M.; Sarr, M.; Soloviov, A.; Rogers, A.; Willoughby, A.; Davenny, K.; Smeriglio, V.; Matzen, E.; Vitiello, B.

In: AIDS, Vol. 16, No. 17, 22.11.2002, p. 2275-2284.

Research output: Contribution to journalArticle

Tang, J, Wilson, CM, Meleth, S, Myracle, A, Lobashevsky, E, Mulligan, MJ, Douglas, SD, Korber, B, Vermund, SH, Kaslow, RA, Friedman, L, Pall, L, Maturo, D, Pasquale, A, Futterman, D, Monte, D, Alovera-DeBellis, M, Hoffman, N, Jackson, S, Schwarz, D, Rudy, B, Tanney, M, Feldman, A, Belzer, M, Tucker, D, Hosmer, C, Chung, K, Abdalian, SE, Green, L, McKendall, C, Wenthold, L, D'Angelo, LJ, Trexler, C, Townsend-Akpan, C, Hagler, R, Morrissy, JA, Peralta, L, Ryder, C, Miller, S, Calianno, S, Henry-Reid, L, Camacho, R, Sturdevant, M, Howell, A, Johnson, JE, Puga, A, Cruz, D, McLendon, P, Sawyer, M, Tigner, J, Simmonds, A, Flynn, P, Lett, K, Dewey, J, Discenza, S, Levin, L, Geiger, M, Stanford, P, Briggs, F, Birnbaum, J, Ramnarine, M, Guarino, V, Holland, C, Moscicki, AB, Murphy, DA, Crowley-Nowick, P, Partlow, C, Durako, SJ, Ellenberg, JH, Hobbs, B, Bennett, A, Camarca, M, Clingan, K, Houser, J, Junankar, V, Leytush, O, Muenz, L, Ma, Y, Mitchell, R, Myint, T, Ohan, P, Paolinelli, L, Rakheja, M, Sarr, M, Soloviov, A, Rogers, A, Willoughby, A, Davenny, K, Smeriglio, V, Matzen, E & Vitiello, B 2002, 'Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents', AIDS, vol. 16, no. 17, pp. 2275-2284. https://doi.org/10.1097/00002030-200211220-00007
Tang J, Wilson CM, Meleth S, Myracle A, Lobashevsky E, Mulligan MJ et al. Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. AIDS. 2002 Nov 22;16(17):2275-2284. https://doi.org/10.1097/00002030-200211220-00007
Tang, Jianming ; Wilson, Craig M. ; Meleth, Shreelatha ; Myracle, Angela ; Lobashevsky, Elena ; Mulligan, Mark J. ; Douglas, Steven D. ; Korber, Bette ; Vermund, Sten H. ; Kaslow, Richard A. ; Friedman, L. ; Pall, L. ; Maturo, D. ; Pasquale, A. ; Futterman, D. ; Monte, D. ; Alovera-DeBellis, M. ; Hoffman, N. ; Jackson, S. ; Schwarz, D. ; Rudy, B. ; Tanney, M. ; Feldman, A. ; Belzer, M. ; Tucker, D. ; Hosmer, C. ; Chung, K. ; Abdalian, S. E. ; Green, L. ; McKendall, C. ; Wenthold, L. ; D'Angelo, L. J. ; Trexler, C. ; Townsend-Akpan, C. ; Hagler, R. ; Morrissy, J. A. ; Peralta, L. ; Ryder, C. ; Miller, S. ; Calianno, S. ; Henry-Reid, L. ; Camacho, R. ; Sturdevant, M. ; Howell, A. ; Johnson, J. E. ; Puga, A. ; Cruz, D. ; McLendon, P. ; Sawyer, M. ; Tigner, J. ; Simmonds, A. ; Flynn, P. ; Lett, K. ; Dewey, J. ; Discenza, S. ; Levin, L. ; Geiger, M. ; Stanford, P. ; Briggs, F. ; Birnbaum, J. ; Ramnarine, M. ; Guarino, V. ; Holland, C. ; Moscicki, A. B. ; Murphy, D. A. ; Crowley-Nowick, P. ; Partlow, C. ; Durako, S. J. ; Ellenberg, J. H. ; Hobbs, B. ; Bennett, A. ; Camarca, M. ; Clingan, K. ; Houser, J. ; Junankar, V. ; Leytush, O. ; Muenz, L. ; Ma, Y. ; Mitchell, R. ; Myint, T. ; Ohan, P. ; Paolinelli, L. ; Rakheja, M. ; Sarr, M. ; Soloviov, A. ; Rogers, A. ; Willoughby, A. ; Davenny, K. ; Smeriglio, V. ; Matzen, E. ; Vitiello, B. / Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. In: AIDS. 2002 ; Vol. 16, No. 17. pp. 2275-2284.
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abstract = "Objective: To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-l-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1 -seropositive adolescents (ages 13-18 years; 75{\%} females; 71{\%} African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6-12-month interval when no antiretroviral therapy was taken. Results: HLA-B* 57 alone was a strong predictor of VL (P <0.0001), but composite genetic profiles found in over 50{\%} of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (<1000 copies/ml) and CD4 T cell counts (> 450 × 106 cells/I) consistently had more positive (+1 to +2) than negative (-1 to -4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells <450 × 106 cells/I) or the remainder (n = 134) of the cohort (overall P <0.0001). Conclusion: A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.",
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author = "Jianming Tang and Wilson, {Craig M.} and Shreelatha Meleth and Angela Myracle and Elena Lobashevsky and Mulligan, {Mark J.} and Douglas, {Steven D.} and Bette Korber and Vermund, {Sten H.} and Kaslow, {Richard A.} and L. Friedman and L. Pall and D. Maturo and A. Pasquale and D. Futterman and D. Monte and M. Alovera-DeBellis and N. Hoffman and S. Jackson and D. Schwarz and B. Rudy and M. Tanney and A. Feldman and M. Belzer and D. Tucker and C. Hosmer and K. Chung and Abdalian, {S. E.} and L. Green and C. McKendall and L. Wenthold and D'Angelo, {L. J.} and C. Trexler and C. Townsend-Akpan and R. Hagler and Morrissy, {J. A.} and L. Peralta and C. Ryder and S. Miller and S. Calianno and L. Henry-Reid and R. Camacho and M. Sturdevant and A. Howell and Johnson, {J. E.} and A. Puga and D. Cruz and P. McLendon and M. Sawyer and J. Tigner and A. Simmonds and P. Flynn and K. Lett and J. Dewey and S. Discenza and L. Levin and M. Geiger and P. Stanford and F. Briggs and J. Birnbaum and M. Ramnarine and V. Guarino and C. Holland and Moscicki, {A. B.} and Murphy, {D. A.} and P. Crowley-Nowick and C. Partlow and Durako, {S. J.} and Ellenberg, {J. H.} and B. Hobbs and A. Bennett and M. Camarca and K. Clingan and J. Houser and V. Junankar and O. Leytush and L. Muenz and Y. Ma and R. Mitchell and T. Myint and P. Ohan and L. Paolinelli and M. Rakheja and M. Sarr and A. Soloviov and A. Rogers and A. Willoughby and K. Davenny and V. Smeriglio and E. Matzen and B. Vitiello",
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TY - JOUR

T1 - Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents

AU - Tang, Jianming

AU - Wilson, Craig M.

AU - Meleth, Shreelatha

AU - Myracle, Angela

AU - Lobashevsky, Elena

AU - Mulligan, Mark J.

AU - Douglas, Steven D.

AU - Korber, Bette

AU - Vermund, Sten H.

AU - Kaslow, Richard A.

AU - Friedman, L.

AU - Pall, L.

AU - Maturo, D.

AU - Pasquale, A.

AU - Futterman, D.

AU - Monte, D.

AU - Alovera-DeBellis, M.

AU - Hoffman, N.

AU - Jackson, S.

AU - Schwarz, D.

AU - Rudy, B.

AU - Tanney, M.

AU - Feldman, A.

AU - Belzer, M.

AU - Tucker, D.

AU - Hosmer, C.

AU - Chung, K.

AU - Abdalian, S. E.

AU - Green, L.

AU - McKendall, C.

AU - Wenthold, L.

AU - D'Angelo, L. J.

AU - Trexler, C.

AU - Townsend-Akpan, C.

AU - Hagler, R.

AU - Morrissy, J. A.

AU - Peralta, L.

AU - Ryder, C.

AU - Miller, S.

AU - Calianno, S.

AU - Henry-Reid, L.

AU - Camacho, R.

AU - Sturdevant, M.

AU - Howell, A.

AU - Johnson, J. E.

AU - Puga, A.

AU - Cruz, D.

AU - McLendon, P.

AU - Sawyer, M.

AU - Tigner, J.

AU - Simmonds, A.

AU - Flynn, P.

AU - Lett, K.

AU - Dewey, J.

AU - Discenza, S.

AU - Levin, L.

AU - Geiger, M.

AU - Stanford, P.

AU - Briggs, F.

AU - Birnbaum, J.

AU - Ramnarine, M.

AU - Guarino, V.

AU - Holland, C.

AU - Moscicki, A. B.

AU - Murphy, D. A.

AU - Crowley-Nowick, P.

AU - Partlow, C.

AU - Durako, S. J.

AU - Ellenberg, J. H.

AU - Hobbs, B.

AU - Bennett, A.

AU - Camarca, M.

AU - Clingan, K.

AU - Houser, J.

AU - Junankar, V.

AU - Leytush, O.

AU - Muenz, L.

AU - Ma, Y.

AU - Mitchell, R.

AU - Myint, T.

AU - Ohan, P.

AU - Paolinelli, L.

AU - Rakheja, M.

AU - Sarr, M.

AU - Soloviov, A.

AU - Rogers, A.

AU - Willoughby, A.

AU - Davenny, K.

AU - Smeriglio, V.

AU - Matzen, E.

AU - Vitiello, B.

PY - 2002/11/22

Y1 - 2002/11/22

N2 - Objective: To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-l-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1 -seropositive adolescents (ages 13-18 years; 75% females; 71% African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6-12-month interval when no antiretroviral therapy was taken. Results: HLA-B* 57 alone was a strong predictor of VL (P <0.0001), but composite genetic profiles found in over 50% of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (<1000 copies/ml) and CD4 T cell counts (> 450 × 106 cells/I) consistently had more positive (+1 to +2) than negative (-1 to -4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells <450 × 106 cells/I) or the remainder (n = 134) of the cohort (overall P <0.0001). Conclusion: A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.

AB - Objective: To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-l-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1 -seropositive adolescents (ages 13-18 years; 75% females; 71% African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6-12-month interval when no antiretroviral therapy was taken. Results: HLA-B* 57 alone was a strong predictor of VL (P <0.0001), but composite genetic profiles found in over 50% of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (<1000 copies/ml) and CD4 T cell counts (> 450 × 106 cells/I) consistently had more positive (+1 to +2) than negative (-1 to -4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells <450 × 106 cells/I) or the remainder (n = 134) of the cohort (overall P <0.0001). Conclusion: A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.

KW - Adolescents

KW - CCR5

KW - Genetics

KW - HIV-1

KW - HLA

KW - Prognosis

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U2 - 10.1097/00002030-200211220-00007

DO - 10.1097/00002030-200211220-00007

M3 - Article

VL - 16

SP - 2275

EP - 2284

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 17

ER -