Estimation of mortality among HIV-infected people on antiretroviral treatment in east Africa: A sampling based approach in an observational, multisite, cohort study

Elvin H. Geng, Thomas A. Odeny, Rita E. Lyamuya, Alice Nakiwogga-Muwanga, Lameck Diero, Mwebesa Bwana, Winnie Muyindike, Paula Braitstein, Geoffrey R. Somi, Andrew Kambugu, Elizabeth A. Bukusi, Megan Wenger, Kara Wools-Kaloustian, David V. Glidden, Constantin Yiannoutsos, Jeffrey N. Martin

Research output: Contribution to journalArticle

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Abstract

Background: Mortality in HIV-infected people after initiation of antiretroviral treatment (ART) in resource-limited settings is an important measure of the effectiveness and comparative effectiveness of the global public health response. Substantial loss to follow-up precludes accurate accounting of deaths and limits our understanding of effectiveness. We aimed to provide a better understanding of mortality at scale and, by extension, the effectiveness and comparative effectiveness of public health ART treatment in east Africa. Methods: In 14 clinics in five settings in Kenya, Uganda, and Tanzania, we intensively traced a sample of patients randomly selected using a random number generator, who were infected with HIV and on ART and who were lost to follow-up (>90 days late for last scheduled visit). We incorporated the vital status outcomes for these patients into analyses of the entire clinic population through probability-weighted survival analyses. Findings: We followed 34 277 adults on ART from Mbarara and Kampala in Uganda, Eldoret, and Kisumu in Kenya, and Morogoro in Tanzania. The median age was 35 years (IQR 30-42), 11 628 (34%) were men, and median CD4 count count before therapy was 154 cells per μL (IQR 70-234). 5780 patients (17%) were lost to follow-up, 991 (17%) were selected for tracing between June 10, 2011, and Aug 27, 2012, and vital status was ascertained for 860 (87%). With incorporation of outcomes from the patients lost to follow-up, estimated 3 year mortality increased from 3·9% (95% CI 3·6-4·2) to 12·5% (11·8-13·3). The sample-corrected, unadjusted 3 year mortality across settings was lowest in Mbarara (7·2%) and highest in Morogoro (23·6%). After adjustment for age, sex, CD4 count before therapy, and WHO stage, the sample-corrected hazard ratio comparing the settings with highest and lowest mortalities was 2·2 (95% CI 1·5-3·4) and the risk difference for death at 3 years was 11% (95% CI 5·0-17·7). Interpretation: A sampling-based approach is widely feasible and important to an understanding of mortality after initiation of ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patients' behaviours driving these differences is urgently needed. Funding: The US National Institutes of Health and President's Emergency Fund for AIDS Relief.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalThe Lancet HIV
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2015

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Eastern Africa
Cohort Studies
HIV
Mortality
Lost to Follow-Up
Uganda
Therapeutics
Tanzania
Kenya
CD4 Lymphocyte Count
Public Health
National Institutes of Health (U.S.)
Survival Analysis
Acquired Immunodeficiency Syndrome
Emergencies

ASJC Scopus subject areas

  • Infectious Diseases
  • Epidemiology
  • Immunology
  • Virology

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Estimation of mortality among HIV-infected people on antiretroviral treatment in east Africa : A sampling based approach in an observational, multisite, cohort study. / Geng, Elvin H.; Odeny, Thomas A.; Lyamuya, Rita E.; Nakiwogga-Muwanga, Alice; Diero, Lameck; Bwana, Mwebesa; Muyindike, Winnie; Braitstein, Paula; Somi, Geoffrey R.; Kambugu, Andrew; Bukusi, Elizabeth A.; Wenger, Megan; Wools-Kaloustian, Kara; Glidden, David V.; Yiannoutsos, Constantin; Martin, Jeffrey N.

In: The Lancet HIV, Vol. 2, No. 3, 01.03.2015, p. 107-116.

Research output: Contribution to journalArticle

Geng, EH, Odeny, TA, Lyamuya, RE, Nakiwogga-Muwanga, A, Diero, L, Bwana, M, Muyindike, W, Braitstein, P, Somi, GR, Kambugu, A, Bukusi, EA, Wenger, M, Wools-Kaloustian, K, Glidden, DV, Yiannoutsos, C & Martin, JN 2015, 'Estimation of mortality among HIV-infected people on antiretroviral treatment in east Africa: A sampling based approach in an observational, multisite, cohort study', The Lancet HIV, vol. 2, no. 3, pp. 107-116. https://doi.org/10.1016/S2352-3018(15)00002-8
Geng, Elvin H. ; Odeny, Thomas A. ; Lyamuya, Rita E. ; Nakiwogga-Muwanga, Alice ; Diero, Lameck ; Bwana, Mwebesa ; Muyindike, Winnie ; Braitstein, Paula ; Somi, Geoffrey R. ; Kambugu, Andrew ; Bukusi, Elizabeth A. ; Wenger, Megan ; Wools-Kaloustian, Kara ; Glidden, David V. ; Yiannoutsos, Constantin ; Martin, Jeffrey N. / Estimation of mortality among HIV-infected people on antiretroviral treatment in east Africa : A sampling based approach in an observational, multisite, cohort study. In: The Lancet HIV. 2015 ; Vol. 2, No. 3. pp. 107-116.
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T2 - A sampling based approach in an observational, multisite, cohort study

AU - Geng, Elvin H.

AU - Odeny, Thomas A.

AU - Lyamuya, Rita E.

AU - Nakiwogga-Muwanga, Alice

AU - Diero, Lameck

AU - Bwana, Mwebesa

AU - Muyindike, Winnie

AU - Braitstein, Paula

AU - Somi, Geoffrey R.

AU - Kambugu, Andrew

AU - Bukusi, Elizabeth A.

AU - Wenger, Megan

AU - Wools-Kaloustian, Kara

AU - Glidden, David V.

AU - Yiannoutsos, Constantin

AU - Martin, Jeffrey N.

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N2 - Background: Mortality in HIV-infected people after initiation of antiretroviral treatment (ART) in resource-limited settings is an important measure of the effectiveness and comparative effectiveness of the global public health response. Substantial loss to follow-up precludes accurate accounting of deaths and limits our understanding of effectiveness. We aimed to provide a better understanding of mortality at scale and, by extension, the effectiveness and comparative effectiveness of public health ART treatment in east Africa. Methods: In 14 clinics in five settings in Kenya, Uganda, and Tanzania, we intensively traced a sample of patients randomly selected using a random number generator, who were infected with HIV and on ART and who were lost to follow-up (>90 days late for last scheduled visit). We incorporated the vital status outcomes for these patients into analyses of the entire clinic population through probability-weighted survival analyses. Findings: We followed 34 277 adults on ART from Mbarara and Kampala in Uganda, Eldoret, and Kisumu in Kenya, and Morogoro in Tanzania. The median age was 35 years (IQR 30-42), 11 628 (34%) were men, and median CD4 count count before therapy was 154 cells per μL (IQR 70-234). 5780 patients (17%) were lost to follow-up, 991 (17%) were selected for tracing between June 10, 2011, and Aug 27, 2012, and vital status was ascertained for 860 (87%). With incorporation of outcomes from the patients lost to follow-up, estimated 3 year mortality increased from 3·9% (95% CI 3·6-4·2) to 12·5% (11·8-13·3). The sample-corrected, unadjusted 3 year mortality across settings was lowest in Mbarara (7·2%) and highest in Morogoro (23·6%). After adjustment for age, sex, CD4 count before therapy, and WHO stage, the sample-corrected hazard ratio comparing the settings with highest and lowest mortalities was 2·2 (95% CI 1·5-3·4) and the risk difference for death at 3 years was 11% (95% CI 5·0-17·7). Interpretation: A sampling-based approach is widely feasible and important to an understanding of mortality after initiation of ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patients' behaviours driving these differences is urgently needed. Funding: The US National Institutes of Health and President's Emergency Fund for AIDS Relief.

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