Browsing by Author "Boulle, Andrew"

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    Adjusting Mortality for Loss to Follow-Up: Analysis of Five ART Programmes in Sub-Saharan Africa
    (Public Library of Science, 2010-11-30) Brinkhof, Martin W. G.; Spycher, Ben D.; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A. C.; Biostatistics, School of Public Health
    Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Methods and Findings Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9–6.5%) to 10.9% (9.6–12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9–11.6%) to 16.9% (15.0–19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. Conclusions Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
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    Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy
    (BMJ, 2012) Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E.; Egger, Matthias; International Epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Objective: To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods: We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results: Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions: Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings.
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    Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration
    (Elsevier, 2019-02) Collins, Intira J.; Wools-Kaloustian, Kara; Goodall, Ruth; Smith, Colette; Abrams, Elaine J.; Ben-Farhat, Jihane; Balkan, Suna; Davies, Mary-Ann; Edmonds, Andrew; Leroy, Valériane; Nuwagaba-Biribonwoha, Harriet; Patel, Kunjal; Paul, Mary E.; Pinto, Jorge; Conejo, Pablo Rojo; Sohn, Annette; Van Dyke, Russell; Vreeman, Rachel; Maxwell, Nicky; Timmerman, Venessa; Duff, Charlotte; Judd, Ali; Seage, George, III; Williams, Paige; Gibb, Diana M.; Bekker, Linda-Gail; Mofenson, Lynne; Vicari, Marissa; Essajee, Shaffiq; Mohapi, Edith Q.; Kazembe, Peter N.; Hlatshwayo, Makhosazana; Lumumba, Mwita; Kekitiinwa-Rukyalekere, Adeodata; Wanless, Sebastian; Matshaba, Mogomotsi S.; Goetghebuer, Tessa; Thorne, Claire; Warszawski, Josiane; Galli, Luisa; Geelen, Sybil; Giaquinto, Carlo; Marczynska, Magdalena; Marques, Laura; Prata, Filipa; Ene, Luminita; Okhonskaia, Liubov; Noguera-Julian, Antoni; Naver, Lars; Rudin, Christoph; Jourdain, Gonzague; Volokha, Alla; Rouzier, Vanessa; Succi, Regina; Chokephaibulkit, Kulkanya; Kariminia, Azar; Yotebieng, Marcel; Lelo, Patricia; Lyamuya, Rita; Marete, Irene; Oyaro, Patrick; Boulle, Andrew; Malisita, Kennedy; Fatti, Geoffrey; Haas, Andreas D.; Desmonde, Sophie; Dicko, Fatoumata; Abzug, Mark J.; Levin, Myron; Oleske, James; Chernoff, Miriam; Traite, Shirley; Purswani, Murli; Teasdale, Chloe; Chadwick, Ellen; Pediatrics, School of Medicine
    Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22-3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations.