Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics

Margaret T May; Robert S Hogg; Antiretroviral Therapy Cohort Collaboration (ART-CC); Amy C Justice; Bryan E Shepherd; Dominique Costagliola; Bruno Ledergerber; Rodolphe Thiébaut; M John Gill; Ole Kirk; Ard van Sighem; Michael S Saag; Gemma Navarro; Paz Sobrino-Vegas; Fiona Lampe; Suzanne Ingle; Jodie L Guest; Heidi M Crane; Antonella D'Arminio Monforte; Jörg J Vehreschild; Jonathan A C Sterne

doi:10.1093/ije/dys164

Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics

Margaret T May^*
, Robert S Hogg
, Antiretroviral Therapy Cohort Collaboration (ART-CC)
, Amy C Justice
, Bryan E Shepherd
, Dominique Costagliola
, Bruno Ledergerber
, Rodolphe Thiébaut
, M John Gill
, Ole Kirk
, Ard van Sighem
, Michael S Saag
, Gemma Navarro
, Paz Sobrino-Vegas
, Fiona Lampe
, Suzanne Ingle
, Jodie L Guest
, Heidi M Crane
, Antonella D'Arminio Monforte
, Jörg J Vehreschild

Jonathan A C Sterne

^*Corresponding author for this work

Bristol Medical School

Research output: Contribution to journal › Article › Academic › peer-review

36 Citations (Scopus)

Abstract

BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.

METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.

RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.

CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.

Original language	English
Pages (from-to)	1807-20
Number of pages	14
Journal	International Journal of Epidemiology
Volume	41
Issue number	6
DOIs	https://doi.org/10.1093/ije/dys164
Publication status	Published - Dec 2012
Externally published	Yes

Bibliographical note

Funding:
M.M. and S.I. were funded by UK Medical Research
Council (grants G0700820 and MR/J002380/1).
Further funding of contributing cohorts was provided
by the Agence Nationale de Recherche contre le SIDA
(ANRS), the Institut National de la Sante´ et de la
Recherche Me´dicale (INSERM), the French, Italian
and Spanish Ministries of Health, the Swiss
National Science Foundation (grant 33CS30_
134277), the Stichting HIV Monitoring, the
European Commission (EuroCoord grant 260694),
the British Columbia and Alberta Governments, the
National Institutes of Health (NIH), UW CFAR (NIH
grant P30 AI027757) USA, the Michael Smith
Foundation for Health Research, the Canadian
Institutes of Health Research, the VHA Office of
Research and Development and unrestricted grants
from GlaxoSmithKline, Pfizer, Bristol Myers Squibb,
Roche and Boehringer-Ingelheim, the UW CFAR (NIH
grant P30 AI027757) and the Spanish Network for
AIDS Research (RIS; ISCIII-RETIC RD06/006).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1093/ije/dys164

Cite this

May, M. T., Hogg, R. S., Antiretroviral Therapy Cohort Collaboration (ART-CC), Justice, A. C., Shepherd, B. E., Costagliola, D., Ledergerber, B., Thiébaut, R., Gill, M. J., Kirk, O., van Sighem, A., Saag, M. S., Navarro, G., Sobrino-Vegas, P., Lampe, F., Ingle, S., Guest, J. L., Crane, H. M., D'Arminio Monforte, A., ... Sterne, J. A. C. (2012). Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics. International Journal of Epidemiology, 41(6), 1807-20. https://doi.org/10.1093/ije/dys164

@article{89dd573b16b04513afbf0c30c87b6af6,

title = "Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics",

abstract = "BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.RESULTS: During 61 520 person-years, 754/38 706 (1.9\%) patients died and 1890 (4.9\%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100\%, good: 90-95\%, average: 75-89\%; mortality rate ratio 0.66 (95\% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.",

author = "May, \{Margaret T\} and Hogg, \{Robert S\} and \{Antiretroviral Therapy Cohort Collaboration (ART-CC)\} and Justice, \{Amy C\} and Shepherd, \{Bryan E\} and Dominique Costagliola and Bruno Ledergerber and Rodolphe Thi{\'e}baut and Gill, \{M John\} and Ole Kirk and \{van Sighem\}, Ard and Saag, \{Michael S\} and Gemma Navarro and Paz Sobrino-Vegas and Fiona Lampe and Suzanne Ingle and Guest, \{Jodie L\} and Crane, \{Heidi M\} and \{D'Arminio Monforte\}, Antonella and Vehreschild, \{J{\"o}rg J\} and Sterne, \{Jonathan A C\}",

note = "Funding: M.M. and S.I. were funded by UK Medical Research Council (grants G0700820 and MR/J002380/1). Further funding of contributing cohorts was provided by the Agence Nationale de Recherche contre le SIDA (ANRS), the Institut National de la Sante´ et de la Recherche Me´dicale (INSERM), the French, Italian and Spanish Ministries of Health, the Swiss National Science Foundation (grant 33CS30\_ 134277), the Stichting HIV Monitoring, the European Commission (EuroCoord grant 260694), the British Columbia and Alberta Governments, the National Institutes of Health (NIH), UW CFAR (NIH grant P30 AI027757) USA, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the VHA Office of Research and Development and unrestricted grants from GlaxoSmithKline, Pfizer, Bristol Myers Squibb, Roche and Boehringer-Ingelheim, the UW CFAR (NIH grant P30 AI027757) and the Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006).",

year = "2012",

month = dec,

doi = "10.1093/ije/dys164",

language = "English",

volume = "41",

pages = "1807--20",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "6",

}

May, MT, Hogg, RS, Antiretroviral Therapy Cohort Collaboration (ART-CC), Justice, AC, Shepherd, BE, Costagliola, D, Ledergerber, B, Thiébaut, R, Gill, MJ, Kirk, O, van Sighem, A, Saag, MS, Navarro, G, Sobrino-Vegas, P, Lampe, F, Ingle, S, Guest, JL, Crane, HM, D'Arminio Monforte, A, Vehreschild, JJ & Sterne, JAC 2012, 'Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics', International Journal of Epidemiology, vol. 41, no. 6, pp. 1807-20. https://doi.org/10.1093/ije/dys164

Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics. / May, Margaret T; Hogg, Robert S; Antiretroviral Therapy Cohort Collaboration (ART-CC) et al.
In: International Journal of Epidemiology, Vol. 41, No. 6, 12.2012, p. 1807-20.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America

T2 - relation with patient and cohort characteristics

AU - May, Margaret T

AU - Hogg, Robert S

AU - Antiretroviral Therapy Cohort Collaboration (ART-CC)

AU - Justice, Amy C

AU - Shepherd, Bryan E

AU - Costagliola, Dominique

AU - Ledergerber, Bruno

AU - Thiébaut, Rodolphe

AU - Gill, M John

AU - Kirk, Ole

AU - van Sighem, Ard

AU - Saag, Michael S

AU - Navarro, Gemma

AU - Sobrino-Vegas, Paz

AU - Lampe, Fiona

AU - Ingle, Suzanne

AU - Guest, Jodie L

AU - Crane, Heidi M

AU - D'Arminio Monforte, Antonella

AU - Vehreschild, Jörg J

AU - Sterne, Jonathan A C

N1 - Funding: M.M. and S.I. were funded by UK Medical Research Council (grants G0700820 and MR/J002380/1). Further funding of contributing cohorts was provided by the Agence Nationale de Recherche contre le SIDA (ANRS), the Institut National de la Sante´ et de la Recherche Me´dicale (INSERM), the French, Italian and Spanish Ministries of Health, the Swiss National Science Foundation (grant 33CS30_ 134277), the Stichting HIV Monitoring, the European Commission (EuroCoord grant 260694), the British Columbia and Alberta Governments, the National Institutes of Health (NIH), UW CFAR (NIH grant P30 AI027757) USA, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the VHA Office of Research and Development and unrestricted grants from GlaxoSmithKline, Pfizer, Bristol Myers Squibb, Roche and Boehringer-Ingelheim, the UW CFAR (NIH grant P30 AI027757) and the Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006).

PY - 2012/12

Y1 - 2012/12

N2 - BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.

AB - BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.

U2 - 10.1093/ije/dys164

DO - 10.1093/ije/dys164

M3 - Article

C2 - 23148105

SN - 0300-5771

VL - 41

SP - 1807

EP - 1820

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 6

ER -

Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics

Abstract

Bibliographical note

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