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 (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/mm(3) 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.

DOI: 10.1093/aje/kwv083

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@inproceedings{Ford2015TheIO, 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}, author={Deborah Ford and James M. Robins and Maya L. Petersen and Diana M. Gibb and Charles F. Gilks and Peter Mugyenyi and Heiner Grosskurth and James Hakim and Elly Katabira and Abdel G. Babiker and A. Sarah Walker and H. Grosskurth and P. Munderi and G. Kabuye and D. Nsibambi and R. Kasirye and E. Zalwango and M. Nakazibwe and B. Kikaire and G. Nassuna and R. Massa and K. Fadhiru and M. Namyalo and A. Zalwango and L. Generous and P. Khauka and N. Rutikarayo and W. Nakahima and A. Mugisha and J. Todd and J. Levin and S. Muyingo and A. Ruberantwari and P. Kaleebu and D. Yirrell and N. Ndembi and F. Lyagoba and P. Hughes and M. Aber and A. Medina Lara and S. Foster and J. Amurwon and B. Nyanzi Wakholi and P. Mugyenyi and C. Kityo and F. Ssali and D. Tumukunde and T. Otim and J. Kabanda and H. Musana and J. Akao and H. Kyomugisha and A. Byamukama and J. Sabiiti and J. Komugyena and P. Wavamunno and S. Mukiibi and A. Drasiku and R. Byaruhanga and O. Labeja and P. Katundu and S. Tugume and P. Awio and A. Namazzi and G. T. Bakeinyaga and H. Katabira and D. Abaine and J. Tukamushaba and W. Anywar and W. Ojiambo and E. Angweng and S. Murungi and W. Haguma and S. Atwiine and J. Kigozi and A. Latif and J. Hakim and V. Robertson and A. Reid and E. Chidziva and R. Bulaya-Tembo and G. Musoro and F. Taziwa and C. Chimbetete and L. Chakonza and A. Mawora and C. Muvirimi and G. Tinago and P. Svovanapasis and M. Simango and O. Chirema and J. Machingura and S. Mutsai and M. Phiri and T. Bafana and M. Chirara and L. Muchabaiwa and M. Muzambi and E. Katabira and A. Ronald and A. Kambungu and F. Lutwama and A. Nanfuka and J. Walusimbi and E. Nabankema and R. Nalumenya and T. Namuli and R. Kulume and I. Namata and L. Nyachwo and A. Florence and A. Kusiima and E. Lubwama and R. Nairuba and F. Oketta and E. Buluma and R. Waita and H. Ojiambo and F. Sadik and J. Wanyama and P. Nabongo and R. Ochai and D. Muhweezi and C. Gilks and K. Boocock and C. Puddephatt and D. Winogron and J. Bohannon and J. Darbyshire and D. M. Gibb and A. Burke and D. Bray and A. Babiker and A. S. Walker and H. Wilkes and M. Rauchenberger and S. Sheehan and L. Peto and K. Taylor and M. Spyer and A. Ferrier and B. Naidoo and D. Dunn and R. Goodall and R. Nanfuka and C. Mufuka-Kapuya and D. Pillay and A. McCormick and I. Weller and S. Bahendeka and M. Bassett and A. Chogo Wapakhabulo and B. Gazzard and C. Mapuchere and O. Mugurungi and C. Burke and S. Jones and C. Newland and S. Rahim and J. Rooney and M. Smith and W. Snowden and J.-M. Steens and A. Breckenridge and A. McLaren and C. Hill and J. Matenga and A. Pozniak and D. Serwadda and T. Peto and A. Palfreeman and M. Borok}, booktitle={American journal of epidemiology}, year={2015} }