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
In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (...
| প্রধান লেখক: | , , , , , , , , , , |
|---|---|
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Oxford University Press
2015
|
| _version_ | 1826256537491865600 |
|---|---|
| author | Ford, D Robins, JM Petersen, ML Gibb, DM Gilks, CF Mugyenyi, P Grosskurth, H Hakim, J Katabira, E Babiker, A Walker, A |
| author_facet | Ford, D Robins, JM Petersen, ML Gibb, DM Gilks, CF Mugyenyi, P Grosskurth, H Hakim, J Katabira, E Babiker, A Walker, A |
| author_sort | Ford, D |
| collection | OXFORD |
| description | In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. 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. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks. |
| first_indexed | 2024-03-06T18:03:48Z |
| format | Journal article |
| id | oxford-uuid:00b9b758-dad1-4cc4-af70-eb03a8e5d89f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:03:48Z |
| publishDate | 2015 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:00b9b758-dad1-4cc4-af70-eb03a8e5d89f2022-03-26T08:31:08ZThe 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 modelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:00b9b758-dad1-4cc4-af70-eb03a8e5d89fEnglishORA DepositOxford University Press2015Ford, DRobins, JMPetersen, MLGibb, DMGilks, CFMugyenyi, PGrosskurth, HHakim, JKatabira, EBabiker, AWalker, AIn Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. 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. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks. |
| spellingShingle | Ford, D Robins, JM Petersen, ML Gibb, DM Gilks, CF Mugyenyi, P Grosskurth, H Hakim, J Katabira, E Babiker, A Walker, A 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| work_keys_str_mv | AT fordd theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT robinsjm theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT petersenml theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT gibbdm theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT gilkscf theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT mugyenyip theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT grosskurthh theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT hakimj theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT katabirae theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT babikera theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT walkera theimpactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT fordd impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT robinsjm impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT petersenml impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT gibbdm impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT gilkscf impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT mugyenyip impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT grosskurthh impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT hakimj impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT katabirae impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT babikera impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels AT walkera impactofdifferentcd4cellcountmonitoringandswitchingstrategiesonmortalityinhivinfectedafricanadultsonantiretroviraltherapyanapplicationofdynamicmarginalstructuralmodels |