TY - JOUR
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 T.
AU - Vittinghoff, Eric V.
AU - Deeks, Steven G.
AU - Martin, Jeffrey N.
N1 - Funding Information:
Funding has been provided by the National Institutes of Health [K23 AI084544, U01 AI069918, U01 AI069919, U01 AI069924, U01 AI069911, U01 AI069907, R01 MH054907 and P30 AI027763] and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Conflict of interest: None declared.
Publisher Copyright:
© The Author 2015.
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
UR - http://www.scopus.com/inward/record.url?scp=84924571062&partnerID=8YFLogxK
U2 - 10.1093/ije/dyu271
DO - 10.1093/ije/dyu271
M3 - Article
C2 - 25859596
AN - SCOPUS:84924571062
SN - 0300-5771
VL - 44
SP - 251
EP - 263
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
IS - 1
ER -