CD4+ T cell recovery during suppression of HIV replication: An international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Elvin H. Geng, Torsten B. Neilands, Rodolphe Thièbaut, Mwebesa Bosco Bwana, Denis Nash, Richard D. Moore, Robin Wood, Djimon Marcel Zannou, Keri N. Althoff, Poh Lian Lim, Jean B. Nachega, Philippa J. Easterbrook, Andrew Kambugu, Francesca Little, Gertrude Nakigozi, Damalie Nakanjako, Valerian Kiggundu, Patrick Chung Ki Li, David R. Bangsberg, Matthew P. FoxHans W. Prozesky, Peter W. Hunt, Mary Ann Davies, Steven J. Reynolds, Matthias Egger, Constantin Yiannoutsos, Eric V. Vittinghoff, Steven G. Deeks, Jeffrey N. Martin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

Original languageEnglish (US)
Pages (from-to)251-263
Number of pages13
JournalInternational Journal of Epidemiology
Volume44
Issue number1
DOIs
StatePublished - Feb 1 2015

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Northern Asia
Northern Africa
North America
HIV
Eastern Africa
T-Lymphocytes
RNA
Confidence Intervals
Southern Africa
Western Africa
efavirenz
CD4 Lymphocyte Count
Therapeutics
Viral Tropism
Nevirapine
RNA-Directed DNA Polymerase
Genetic Therapy
Linear Models
Demography
Antigens

Keywords

  • Africa
  • Antiretroviral therapy
  • CD4+T cell counts
  • HIV
  • Immunological activation

ASJC Scopus subject areas

  • Epidemiology

Cite this

CD4+ T cell recovery during suppression of HIV replication : An international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa. / Geng, Elvin H.; Neilands, Torsten B.; Thièbaut, Rodolphe; Bwana, Mwebesa Bosco; Nash, Denis; Moore, Richard D.; Wood, Robin; Zannou, Djimon Marcel; Althoff, Keri N.; Lim, Poh Lian; Nachega, Jean B.; Easterbrook, Philippa J.; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Li, Patrick Chung Ki; Bangsberg, David R.; Fox, Matthew P.; Prozesky, Hans W.; Hunt, Peter W.; Davies, Mary Ann; Reynolds, Steven J.; Egger, Matthias; Yiannoutsos, Constantin; Vittinghoff, Eric V.; Deeks, Steven G.; Martin, Jeffrey N.

In: International Journal of Epidemiology, Vol. 44, No. 1, 01.02.2015, p. 251-263.

Research output: Contribution to journalArticle

Geng, EH, Neilands, TB, Thièbaut, R, Bwana, MB, Nash, D, Moore, RD, Wood, R, Zannou, DM, Althoff, KN, Lim, PL, Nachega, JB, Easterbrook, PJ, Kambugu, A, Little, F, Nakigozi, G, Nakanjako, D, Kiggundu, V, Li, PCK, Bangsberg, DR, Fox, MP, Prozesky, HW, Hunt, PW, Davies, MA, Reynolds, SJ, Egger, M, Yiannoutsos, C, Vittinghoff, EV, Deeks, SG & Martin, JN 2015, 'CD4+ T cell recovery during suppression of HIV replication: An international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa', International Journal of Epidemiology, vol. 44, no. 1, pp. 251-263. https://doi.org/10.1093/ije/dyu271
Geng, Elvin H. ; Neilands, Torsten B. ; Thièbaut, Rodolphe ; Bwana, Mwebesa Bosco ; Nash, Denis ; Moore, Richard D. ; Wood, Robin ; Zannou, Djimon Marcel ; Althoff, Keri N. ; Lim, Poh Lian ; Nachega, Jean B. ; Easterbrook, Philippa J. ; Kambugu, Andrew ; Little, Francesca ; Nakigozi, Gertrude ; Nakanjako, Damalie ; Kiggundu, Valerian ; Li, Patrick Chung Ki ; Bangsberg, David R. ; Fox, Matthew P. ; Prozesky, Hans W. ; Hunt, Peter W. ; Davies, Mary Ann ; Reynolds, Steven J. ; Egger, Matthias ; Yiannoutsos, Constantin ; Vittinghoff, Eric V. ; Deeks, Steven G. ; Martin, Jeffrey N. / CD4+ T cell recovery during suppression of HIV replication : An international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa. In: International Journal of Epidemiology. 2015 ; Vol. 44, No. 1. pp. 251-263.
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T1 - CD4+ T cell recovery during suppression of HIV replication

T2 - An international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

AU - Geng, Elvin H.

AU - Neilands, Torsten B.

AU - Thièbaut, Rodolphe

AU - Bwana, Mwebesa Bosco

AU - Nash, Denis

AU - Moore, Richard D.

AU - Wood, Robin

AU - Zannou, Djimon Marcel

AU - Althoff, Keri N.

AU - Lim, Poh Lian

AU - Nachega, Jean B.

AU - Easterbrook, Philippa J.

AU - Kambugu, Andrew

AU - Little, Francesca

AU - Nakigozi, Gertrude

AU - Nakanjako, Damalie

AU - Kiggundu, Valerian

AU - Li, Patrick Chung Ki

AU - Bangsberg, David R.

AU - Fox, Matthew P.

AU - Prozesky, Hans W.

AU - Hunt, Peter W.

AU - Davies, Mary Ann

AU - Reynolds, Steven J.

AU - Egger, Matthias

AU - Yiannoutsos, Constantin

AU - Vittinghoff, Eric V.

AU - Deeks, Steven G.

AU - Martin, Jeffrey N.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

AB - Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

KW - Africa

KW - Antiretroviral therapy

KW - CD4+T cell counts

KW - HIV

KW - Immunological activation

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DO - 10.1093/ije/dyu271

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