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The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models.

Ford D, Robins JM, Petersen ML, Gibb DM, Gilks CF, Mugyenyi P, Grosskurth H, Hakim J, Katabira E, Babiker AG, Walker AS, DART Trial Te - Am. J. Epidemiol. (2015)

Bottom Line: Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates.After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths.These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.

View Article: PubMed Central - PubMed

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Survival among human immunodeficiency virus–positive patients on antiretroviral therapy (ART) for different CD4 cell-count monitoring strategies, all assuming a switch in treatment regimen (to second-line ART) at the first observed CD4 count less than 100 cells/mm3 or the first non-Candida World Health Organization stage 4 event (with CD4 count <250), estimated by means of dynamic marginal structural models, Development of Antiretroviral Therapy in Africa (DART) Trial, Uganda and Zimbabwe, 2003–2008. Baseline was 48 consecutive weeks on first-line ART.
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KWV083F2: Survival among human immunodeficiency virus–positive patients on antiretroviral therapy (ART) for different CD4 cell-count monitoring strategies, all assuming a switch in treatment regimen (to second-line ART) at the first observed CD4 count less than 100 cells/mm3 or the first non-Candida World Health Organization stage 4 event (with CD4 count <250), estimated by means of dynamic marginal structural models, Development of Antiretroviral Therapy in Africa (DART) Trial, Uganda and Zimbabwe, 2003–2008. Baseline was 48 consecutive weeks on first-line ART.

Mentions: Under a strategy defined by switching at the first CD4 count <100 or non-Candida WHO 4 event (CD4 <250), we found no survival advantage at 240 weeks for 12-weekly CD4 counts as compared with 24-weekly CD4 counts (−0.2%, 95% CI: −1.4, 0.7) and observed only small, nonsignificant survival advantages for 12-weekly CD4 counts compared with less frequent CD4-monitoring strategies, including a single (baseline) CD4 count 48 weeks after ART initiation (0.9% (95% CI: −1.0, 2.7) at 240 weeks) (Table 3, Figure 2). Compared with no CD4 monitoring, the survival benefit derived from a single CD4 count after 48 weeks of first-line ART was significant (2.4% (95% CI: 1.3, 3.9) at 240 weeks). Under 12-weekly CD4 counts, 2.2% of follow-up would be spent with CD4 count <100 as compared with 2.7% and 3.6% under 24-weekly and 48-weekly CD4 counts, 6.6% with a single CD4 count after 48 weeks of first-line ART, and 9.4% with no CD4 monitoring (Web Figure 2). A single CD4 count after 48 weeks of first-line ART improved survival at 240 weeks by 1.2% (95% CI: 0.2, 2.3) and 1.9% (95% CI: 0.7, 3.5) as compared with a single CD4 count after 72 and 96 weeks of first-line ART, respectively.Figure 2.


The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models.

Ford D, Robins JM, Petersen ML, Gibb DM, Gilks CF, Mugyenyi P, Grosskurth H, Hakim J, Katabira E, Babiker AG, Walker AS, DART Trial Te - Am. J. Epidemiol. (2015)

Survival among human immunodeficiency virus–positive patients on antiretroviral therapy (ART) for different CD4 cell-count monitoring strategies, all assuming a switch in treatment regimen (to second-line ART) at the first observed CD4 count less than 100 cells/mm3 or the first non-Candida World Health Organization stage 4 event (with CD4 count <250), estimated by means of dynamic marginal structural models, Development of Antiretroviral Therapy in Africa (DART) Trial, Uganda and Zimbabwe, 2003–2008. Baseline was 48 consecutive weeks on first-line ART.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581589&req=5

KWV083F2: Survival among human immunodeficiency virus–positive patients on antiretroviral therapy (ART) for different CD4 cell-count monitoring strategies, all assuming a switch in treatment regimen (to second-line ART) at the first observed CD4 count less than 100 cells/mm3 or the first non-Candida World Health Organization stage 4 event (with CD4 count <250), estimated by means of dynamic marginal structural models, Development of Antiretroviral Therapy in Africa (DART) Trial, Uganda and Zimbabwe, 2003–2008. Baseline was 48 consecutive weeks on first-line ART.
Mentions: Under a strategy defined by switching at the first CD4 count <100 or non-Candida WHO 4 event (CD4 <250), we found no survival advantage at 240 weeks for 12-weekly CD4 counts as compared with 24-weekly CD4 counts (−0.2%, 95% CI: −1.4, 0.7) and observed only small, nonsignificant survival advantages for 12-weekly CD4 counts compared with less frequent CD4-monitoring strategies, including a single (baseline) CD4 count 48 weeks after ART initiation (0.9% (95% CI: −1.0, 2.7) at 240 weeks) (Table 3, Figure 2). Compared with no CD4 monitoring, the survival benefit derived from a single CD4 count after 48 weeks of first-line ART was significant (2.4% (95% CI: 1.3, 3.9) at 240 weeks). Under 12-weekly CD4 counts, 2.2% of follow-up would be spent with CD4 count <100 as compared with 2.7% and 3.6% under 24-weekly and 48-weekly CD4 counts, 6.6% with a single CD4 count after 48 weeks of first-line ART, and 9.4% with no CD4 monitoring (Web Figure 2). A single CD4 count after 48 weeks of first-line ART improved survival at 240 weeks by 1.2% (95% CI: 0.2, 2.3) and 1.9% (95% CI: 0.7, 3.5) as compared with a single CD4 count after 72 and 96 weeks of first-line ART, respectively.Figure 2.

Bottom Line: Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates.After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths.These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.

View Article: PubMed Central - PubMed

Show MeSH
Related in: MedlinePlus