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. 2013 May 1;63(1):105-11.
doi: 10.1097/QAI.0b013e3182893fb4.

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

Christopher J Hoffmann  1 , James J Lewis, David W Dowdy, Katherine L Fielding, Alison D Grant, Neil A Martinson, Gavin J Churchyard, Richard E Chaisson
Affiliations

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

Christopher J Hoffmann et al. J Acquir Immune Defic Syndr. .

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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Conflict of interest statement

Conflicts of interest: All authors, no conflicts

Figures

Figure 1
Figure 1
Markov state transition model with CD4 states and arrows indicating the allowed transitions between states for a cohort followed for 52 weeks from clinic entry and initiating ART at week “k”. Mortality occurs from each state each cycle. Before ART initiation, transitions can occur between adjacent CD4 count states. After ART initiation, mortality is estimated as a function of CD4 count state at ART initiation and weeks since ART initiation, and thus there are no transitions between CD4 count states and the boxes are blank because individual patients may have a wide range of CD4 counts.
Figure 2
Figure 2
Contour plot of total mortality risk 52 weeks after entering HIV care by duration of delay in ART initiation (x-axis) and CD4 at care entry (y-axis). CD4 at the time of entry into care is on the y-axis, delay in ART initiation on the x-axis, and contours represent mortality bands by percent of the cohort who died 52 weeks after entering care. The close contour lines at lower entry CD4 represent the more rapid increase in mortality with delays among such patients. The black line represents the increasing mortality with the whole cohort analysis (median CD4 count 143 cells/mm3) in which mortality increases from 11.0% with no delay to 19.7% with a 26 week delay and 24.2% with a 52 week delay.
Figure 3
Figure 3
Tornado diagram of absolute change in percent mortality at 10 weeks and 26 weeks with a 25% decrease or 25% increase in parameter for CD4 transition, pre-ART mortality, or on-ART mortality.
See this image and copyright information in PMC

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