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Overestimates of survival after HAART: implications for global scale-up efforts.

Bisson GP, Gaolathe T, Gross R, Rollins C, Bellamy S, Mogorosi M, Avalos A, Friedman H, Dickinson D, Frank I, Ndwapi N - PLoS ONE (2008)

Bottom Line: Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation.Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing.Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88-0.94 before tracing and 0.83 (95% confidence interval, 0.79-0.86) after tracing, log rank P<0.001].

View Article: PubMed Central - PubMed

Affiliation: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. gregbisson@mac.com

ABSTRACT

Background: Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation. Determining definitive outcomes of these lost patients, and the effects of losses to follow-up on estimates of survival and risk factors for death after HAART, are key to monitoring the effectiveness of global HAART scale-up efforts.

Methodology/principal findings: A cohort study comparing clinical outcomes and risk factors for death after HAART initiation as reported before and after tracing of patients lost to follow-up was conducted in Botswana's National Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting for HAART were evaluated. The main outcome measures were death or loss to follow-up within the first year after HAART initiation. Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88-0.94 before tracing and 0.83 (95% confidence interval, 0.79-0.86) after tracing, log rank P<0.001]. In addition, a significantly increased risk of death after HAART among men [adjusted hazard ratio 1.74 (95% confidence interval, 1.05-2.87)] would have been missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence interval, 0.65-3.05)].

Conclusions/significance: Due to high rates of death among patients lost to follow-up after HAART, survival rates may be inaccurate and important risk factors for death may be missed if patients are not actively traced. Patient tracing and uniform reporting of outcomes after HAART are needed to enable accurate monitoring of global HAART scale-up efforts.

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Kaplan-Meier curve 52-week survival estimates before and after patient tracing, IDCC, Gaborone, Botswana.Losses to follow-up are censored. Log rank P <0.001.
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pone-0001725-g001: Kaplan-Meier curve 52-week survival estimates before and after patient tracing, IDCC, Gaborone, Botswana.Losses to follow-up are censored. Log rank P <0.001.

Mentions: 410 patients contributed 317 patient-years of follow-up; the median duration of follow-up among patients on HAART was 44 weeks (inter-quartile range (IQR), 37–49). Of the 68 patients who were originally lost to follow-up, 65 (96%) were called and 19 (28%) were visited. Patient tracing significantly increased the number of reported deaths [29 of 410 (7.1%) vs. 69 of 410 (16.8%); P<0.001 for difference in proportion reported dead]. Of the 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing (Table 2), and 57.9% (40 of 69) of all deaths after HAART were initially categorized as lost to follow-up. The median survival time after HAART for those who were characterized as lost before tracing and then confirmed dead after tracing was 47 days (IQR, 24–98 days). Furthermore, the median pre-treatment CD4 cell count of the 22 patients who remained lost to follow-up after tracing was significantly lower compared to pre-treatment CD4 counts of patients remaining alive and in care [37 cells/mm3 (IQR 17–77) vs. 98 (IQR 38–158), rank sum P = 0.009]. The 1-year Kaplan-Meier survival estimates before and after tracing are shown in Figure 1. Patient tracing resulted in reporting of a significantly lower estimate of survival than was observed before tracing [log rank P<0.001, Figure 1]. This effect can be attributed to an increased number of ascertained deaths in the setting of an unchanged number of patients at risk after tracing (Table 2).


Overestimates of survival after HAART: implications for global scale-up efforts.

Bisson GP, Gaolathe T, Gross R, Rollins C, Bellamy S, Mogorosi M, Avalos A, Friedman H, Dickinson D, Frank I, Ndwapi N - PLoS ONE (2008)

Kaplan-Meier curve 52-week survival estimates before and after patient tracing, IDCC, Gaborone, Botswana.Losses to follow-up are censored. Log rank P <0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2254493&req=5

pone-0001725-g001: Kaplan-Meier curve 52-week survival estimates before and after patient tracing, IDCC, Gaborone, Botswana.Losses to follow-up are censored. Log rank P <0.001.
Mentions: 410 patients contributed 317 patient-years of follow-up; the median duration of follow-up among patients on HAART was 44 weeks (inter-quartile range (IQR), 37–49). Of the 68 patients who were originally lost to follow-up, 65 (96%) were called and 19 (28%) were visited. Patient tracing significantly increased the number of reported deaths [29 of 410 (7.1%) vs. 69 of 410 (16.8%); P<0.001 for difference in proportion reported dead]. Of the 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing (Table 2), and 57.9% (40 of 69) of all deaths after HAART were initially categorized as lost to follow-up. The median survival time after HAART for those who were characterized as lost before tracing and then confirmed dead after tracing was 47 days (IQR, 24–98 days). Furthermore, the median pre-treatment CD4 cell count of the 22 patients who remained lost to follow-up after tracing was significantly lower compared to pre-treatment CD4 counts of patients remaining alive and in care [37 cells/mm3 (IQR 17–77) vs. 98 (IQR 38–158), rank sum P = 0.009]. The 1-year Kaplan-Meier survival estimates before and after tracing are shown in Figure 1. Patient tracing resulted in reporting of a significantly lower estimate of survival than was observed before tracing [log rank P<0.001, Figure 1]. This effect can be attributed to an increased number of ascertained deaths in the setting of an unchanged number of patients at risk after tracing (Table 2).

Bottom Line: Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation.Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing.Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88-0.94 before tracing and 0.83 (95% confidence interval, 0.79-0.86) after tracing, log rank P<0.001].

View Article: PubMed Central - PubMed

Affiliation: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. gregbisson@mac.com

ABSTRACT

Background: Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation. Determining definitive outcomes of these lost patients, and the effects of losses to follow-up on estimates of survival and risk factors for death after HAART, are key to monitoring the effectiveness of global HAART scale-up efforts.

Methodology/principal findings: A cohort study comparing clinical outcomes and risk factors for death after HAART initiation as reported before and after tracing of patients lost to follow-up was conducted in Botswana's National Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting for HAART were evaluated. The main outcome measures were death or loss to follow-up within the first year after HAART initiation. Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88-0.94 before tracing and 0.83 (95% confidence interval, 0.79-0.86) after tracing, log rank P<0.001]. In addition, a significantly increased risk of death after HAART among men [adjusted hazard ratio 1.74 (95% confidence interval, 1.05-2.87)] would have been missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence interval, 0.65-3.05)].

Conclusions/significance: Due to high rates of death among patients lost to follow-up after HAART, survival rates may be inaccurate and important risk factors for death may be missed if patients are not actively traced. Patient tracing and uniform reporting of outcomes after HAART are needed to enable accurate monitoring of global HAART scale-up efforts.

Show MeSH