eprintid: 1373451 rev_number: 55 eprint_status: archive userid: 608 dir: disk0/01/37/34/51 datestamp: 2012-11-29 15:28:05 lastmod: 2021-12-05 01:09:48 status_changed: 2015-11-02 14:24:57 type: article metadata_visibility: show item_issues_count: 0 creators_name: Ford, DJ creators_name: Robins, J creators_name: Petersen, M creators_name: Gibb, DM creators_name: Gilks, CF creators_name: Mugyenyi, P creators_name: Grosskurth, H creators_name: Hakim, J creators_name: Katabira, E creators_name: Babiker, AG creators_name: Walker, AS title: The impact of different CD4 monitoring and switching strategies on mortality in HIV-infected African adults on antiretroviral therapy; an application of dynamic marginal structural models ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 note: © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: 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. date: 2015-08-26 official_url: http://dx.doi.org/10.1093/aje/kwv083 oa_status: green full_text_type: pub language: eng article_type_text: Article verified: verified_manual elements_source: Manually entered elements_id: 830253 doi: 10.1093/aje/kwv083 publication_declined: 2015-04-16T21:03:05BST lyricists_name: Babiker, Abdel lyricists_name: Ford, Deborah lyricists_name: Gibb, Diana lyricists_name: Walker, Ann lyricists_id: ABABI41 lyricists_id: DFORD95 lyricists_id: MGIBB48 lyricists_id: ASWAL40 full_text_status: public publication: American Journal of Epidemiology volume: 182 number: 7 citation: Ford, DJ; Robins, J; Petersen, M; Gibb, DM; Gilks, CF; Mugyenyi, P; Grosskurth, H; ... Walker, AS; + view all <#> Ford, DJ; Robins, J; Petersen, M; Gibb, DM; Gilks, CF; Mugyenyi, P; Grosskurth, H; Hakim, J; Katabira, E; Babiker, AG; Walker, AS; - view fewer <#> (2015) The impact of different CD4 monitoring and switching strategies on mortality in HIV-infected African adults on antiretroviral therapy; an application of dynamic marginal structural models. American Journal of Epidemiology , 182 (7) 10.1093/aje/kwv083 <https://doi.org/10.1093/aje%2Fkwv083>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1373451/4/The%20Impact%20of%20Different%20CD4%20Cell-Count%20Monitoring%20and%20Switching%20Strategies%20on%20Mortality%20in%20HIV-Infected%20African%20Adults%20on%20Antiretroviral%20Therapy%3A%20An%20Application%20of%20Dynamic%20Marginal%20Structural%20Models..pdf