Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: Results of a transition-state model

Christopher Hoffmann, James J. Lewis, David Wesley Dowdy, Katherine L. Fielding, Alison D. Grant, Neil A. Martinson, Gavin J. Churchyard, Richard E Chaisson

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume63
Issue number1
DOIs
StatePublished - May 1 2013

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Mortality
Therapeutics
CD4 Lymphocyte Count
Markov Chains
Patient Care
HIV
Costs and Cost Analysis
Population

Keywords

  • Africa
  • ART delay
  • CD4 count
  • mortality
  • state-transition model

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Mortality associated with delays between clinic entry and ART initiation in resource-limited settings : Results of a transition-state model. / Hoffmann, Christopher; Lewis, James J.; Dowdy, David Wesley; Fielding, Katherine L.; Grant, Alison D.; Martinson, Neil A.; Churchyard, Gavin J.; Chaisson, Richard E.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 63, No. 1, 01.05.2013, p. 105-111.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0{\%} to 14.7{\%} (relative increase of 34{\%}) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3{\%} with no delay compared with 17.0{\%} with a 10-week delay and 22.9{\%} with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.",
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AU - Hoffmann, Christopher

AU - Lewis, James J.

AU - Dowdy, David Wesley

AU - Fielding, Katherine L.

AU - Grant, Alison D.

AU - Martinson, Neil A.

AU - Churchyard, Gavin J.

AU - Chaisson, Richard E

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N2 - OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.

AB - OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.

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