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 Team, ; , COLLABORATORS; Grosskurth, H; Munderi, P; Kabuye, G; Nsibambi, D; Kasirye, R; Zalwango, E; Nakazibwe, M; Kikaire, B; Nassuna, G; Massa, R; Fadhiru, K; Namyalo, M; Zalwango, A; Generous, L; Khauka, P; Rutikarayo, N; Nakahima, W; Mugisha, A; Todd, J; Levin, J; Muyingo, S; Ruberantwari, A; Kaleebu, P; Yirrell, D; Ndembi, N; Lyagoba, F; Hughes, P; Aber, M; Medina Lara, A; Foster, S; Amurwon, J; Nyanzi Wakholi, B; Mugyenyi, P; Kityo, C; Ssali, F; Tumukunde, D; Otim, T; Kabanda, J; Musana, H; Akao, J; Kyomugisha, H; Byamukama, A; Sabiiti, J; Komugyena, J; Wavamunno, P; Mukiibi, S; Drasiku, A; Byaruhanga, R; Labeja, O; Katundu, P; Tugume, S; Awio, P; Namazzi, A; Bakeinyaga, GT; Katabira, H; Abaine, D; Tukamushaba, J; Anywar, W; Ojiambo, W; Angweng, E; Murungi, S; Haguma, W; Atwiine, S; Kigozi, J; Latif, A; Hakim, J; Robertson, V; Reid, A; Chidziva, E; Bulaya-Tembo, R; Musoro, G; Taziwa, F; Chimbetete, C; Chakonza, L; Mawora, A; Muvirimi, C; Tinago, G; Svovanapasis, P; Simango, M; Chirema, O; Machingura, J; Mutsai, S; Phiri, M; Bafana, T; Chirara, M; Muchabaiwa, L; Muzambi, M; Katabira, E; Ronald, A; Kambungu, A; Lutwama, F; Nanfuka, A; Walusimbi, J; Nabankema, E; Nalumenya, R; Namuli, T; Kulume, R; Namata, I; Nyachwo, L; Florence, A; Kusiima, A; Lubwama, E; Nairuba, R; Oketta, F; Buluma, E; Waita, R; Ojiambo, H; Sadik, F; Wanyama, J; Nabongo, P; Ochai, R; Muhweezi, D; Gilks, C; Boocock, K; Puddephatt, C; Winogron, D; Bohannon, J; Darbyshire, J; Gibb, DM; Burke, A; Bray, D; Babiker, A; Walker, AS; Wilkes, H; Rauchenberger, M; Sheehan, S; Peto, L; Taylor, K; Spyer, M; Ferrier, A; Naidoo, B; Dunn, D; Goodall, R; Nanfuka, R; Mufuka-Kapuya, C; Kaleebu, P; Pillay, D; Robertson, V; Yirrell, D; Tugume, S; Chirara, M; Katundu, P; Ndembi, N; Lyagoba, F; Dunn, D; Goodall, R; McCormick, A; Medina Lara, A; Foster, S; Amurwon, J; Nyanzi Wakholi, B; Kigozi, J; Muchabaiwa, L; Muzambi, M; Weller, I; Babiker, A; Bahendeka, S; Bassett, M; Chogo Wapakhabulo, A; Darbyshire, J; Gazzard, B; Gilks, C; Grosskurth, H; Hakim, J; Latif, A; Mapuchere, C; Mugurungi, O; Mugyenyi, P; Burke, C; Jones, S; Newland, C; Rahim, S; Rooney, J; Smith, M; Snowden, W; Steens, JM; Breckenridge, A; McLaren, A; Hill, C; Matenga, J; Pozniak, A; Serwadda, D; Peto, T; Palfreeman, A; Borok, M; Katabira, E; (2015) 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. American journal of epidemiology, 182 (7). pp. 633-43. ISSN 0002-9262 DOI: https://doi.org/10.1093/aje/kwv083

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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/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count &lt;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 &lt;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.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: HIV Research Group
Tropical Epidemiology Group
PubMed ID: 26316598
Web of Science ID: 361811100010
URI: http://researchonline.lshtm.ac.uk/id/eprint/2287473

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