Browsing by Author "Egger, Matthias"
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Item 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 HealthEvaluation 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.Item Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis(Oxford University Press, 2021) Brazier, Ellen; Tymejczyk, Olga; Zaniewski, Elizabeth; Egger, Matthias; Wools-Kaloustian, Kara; Yiannoutsos, Constantin T.; Jaquet, Antoine; Althoff, Keri N.; Lee, Jennifer S.; Caro-Vega, Yanink; Luz, Paula M.; Tanuma, Junko; Niyongabo, Théodore; Nash, Denis; Medicine, School of MedicineBackground: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. Methods: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). Results: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. Conclusions: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.Item Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries(Elsevier, 2021) Han, Win Min; Law, Matthew G.; Egger, Matthias; Wools-Kaloustian, Kara; Moore, Richard; McGowan, Catherine; Kumarasamy, Nagalingesawaran; Desmonde, Sophie; Edmonds, Andrew; Davies, Mary-Ann; Yiannoutsos, Constantin; Althoff, Keri N.; Cortes, Claudia P.; Mohamed, Thahira Jamal; Jaquet, Antoine; Anastos, Kathryn; Euvrard, Jonathan; Castelnuovo, Barbara; Salters, Kate; Esteves Coelho, Lara; Ekouevi, Didier K.; Eley, Brian; Diero, Lameck; Zaniewski, Elizabeth; Ford, Nathan; Sohn, Annette H.; Kariminia, Azar; IeDEA collaboration; Medicine, School of MedicineBackground: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents.Item Global variations in mortality in adults after initiating antiretroviral treatment: an updated analysis of the International epidemiology Databases to Evaluate AIDS cohort collaboration(Wolters Kluwer, 2019-12-15) Johnson, Leigh F.; Anderegg, Nanina; Zaniewski, Elizabeth; Eaton, Jeffrey W.; Rebeiro, Peter F.; Carriquiry, Gabriela; Nash, Denis; Yotebieng, Marcel; Ekouevi, Didier K.; Holmes, Charles B.; Choi, Jun Y.; Jiamsakul, Awachana; Bakoyannis, Giorgos; Althoff, Keri N.; Sohn, Annette H.; Yiannoutsos, Constantin; Egger, Matthias; Biostatistics, School of Public HealthBackground: UNAIDS models use data from the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration in setting assumptions about mortality rates after antiretroviral treatment (ART) initiation. This study aims to update these assumptions with new data, to quantify the extent of regional variation in ART mortality and to assess trends in ART mortality. Methods: Adult ART patients from Africa, Asia and the Americas were included if they had a known date of ART initiation during 2001-2017 and a baseline CD4 cell count. In cohorts that relied only on passive follow-up (no patient tracing or linkage to vital registration systems), mortality outcomes were imputed in patients lost to follow-up based on a meta-analysis of tracing study data. Poisson regression models were fitted to the mortality data. Results: 464 048 ART patients were included. In multivariable analysis, mortality rates were lowest in Asia and highest in Africa, with no significant differences between African regions. Adjusted mortality rates varied significantly between programmes within regions. Mortality rates in the first 12 months after ART initiation were significantly higher during 2001-2006 than during 2010-2014, although the difference was more substantial in Asia and the Americas [adjusted incidence rate ratio (aIRR) 1.43, 95% CI: 1.22-1.66] than in Africa (aIRR 1.07, 95% CI: 1.04-1.11). Conclusion: There is substantial variation in ART mortality between and within regions, even after controlling for differences in mortality by age, sex, baseline CD4 category and calendar period. ART mortality rates have declined substantially over time, although declines have been slower in Africa.Item High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study(Wolters Kluwer, 2022-12-15) Nyakato, Patience; Christ, Benedikt; Anderegg, Nanina; Muhairwe, Josephine; Jefferys, Laura; van Dijk, Janneke; Vinikoor, Michael J.; van Lettow, Monique; Chimbetete, Cleophas; Phiri, Sam J.; Egger, Matthias; Ballif, Marie; Yiannoutsos, Constantin T.; Schomaker, Michael; Kassanjee, Reshma; Davies, Mary-Ann; Cornell, Morna; International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA); Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. Methods: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. Results: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20–24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. Conclusions: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.Item Impact of the COVID-19 pandemic on TB services at ART programmes in low- and middle-income countries: a multi-cohort survey(Wiley, 2022) Marti, Mariana; Zürcher, Kathrin; Enane, Leslie A.; Diero, Lameck; Marcy, Olivier; Tiendrebeogo, Thierry; Yotebieng, Marcel; Twizere, Christelle; Khusuwan, Suwimon; Yunihastuti, Evy; Reubenson, Gary; Shah, N. Sarita; Egger, Matthias; Ballif, Marie; Fenner, Lukas; IeDEA global consortium; Pediatrics, School of MedicineIntroduction: COVID-19 stretched healthcare systems to their limits, particularly in settings with a pre-existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID-19 on TB services at antiretroviral therapy (ART) clinics in low- and middle-income countries. Methods: We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia-Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site-level data using standardized questionnaires. Results: Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia-Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia-Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow-up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia-Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (-8%) but not in the Asia-Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage. Conclusions: The COVID-19 pandemic led to staff shortages, reduced access to TB care and delays in follow-up visits for people with TB across IeDEA sites in Africa and the Asia-Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts.Item Integrating services for HIV and multidrug-resistant tuberculosis: A global cross-sectional survey among ART clinics in low- and middle-income countries(PLOS, 2022-03) Zürcher, Kathrin; Cox, Samyra R.; Ballif, Marie; Enane, Leslie A.; Marcy, Olivier; Yotebieng, Marcel; Reubenson, Gary; Imsanguan, Worarat; Otero, Larissa; Suryavanshi, Nishi; Duda, Stephany N.; Egger, Matthias; Tornheim, Jeffrey A.; Fenner, Lukas; International Epidemiology Databases to Evaluate AIDS (IeDEA); Pediatrics, School of MedicineTuberculosis (TB) is the leading cause of death among PLHIV and multidrug-resistant-TB (MDR-TB) is associated with high mortality. We examined the management for adult PLHIV coinfected with MDR-TB at ART clinics in lower income countries. Between 2019 and 2020, we conducted a cross-sectional survey at 29 ART clinics in high TB burden countries within the global IeDEA network. We used structured questionnaires to collect clinic-level data on the TB and HIV services and the availability of diagnostic tools and treatment for MDR-TB. Of 29 ART clinics, 25 (86%) were in urban areas and 19 (66%) were tertiary care clinics. Integrated HIV-TB services were reported at 25 (86%) ART clinics for pan-susceptible TB, and 14 (48%) clinics reported full MDR-TB services on-site, i.e. drug susceptibility testing [DST] and MDR-TB treatment. Some form of DST was available on-site at 22 (76%) clinics, while the remainder referred testing off-site. On-site DST for second-line drugs was available at 9 (31%) clinics. MDR-TB treatment was delivered on-site at 15 (52%) clinics, with 10 individualizing treatment based on DST results and five using standardized regimens alone. Bedaquiline was routinely available at 5 (17%) clinics and delamanid at 3 (10%) clinics. Although most ART clinics reported having integrated HIV and TB services, few had fully integrated MDR-TB services. There is a continued need for increased access to diagnostic and treatment options for MDR-TB patients and better integration of MDR-TB services into the HIV care continuum.Item International epidemiology databases to evaluate AIDS (IeDEA) in sub-Saharan Africa, 2012–2019(BMJ Publishing Group, 2020-05-15) Chammartin, Frédérique; Dao Ostinelli, Cam Ha; Anastos, Kathryn; Jaquet, Antoine; Brazier, Ellen; Brown, Steven; Dabis, Francois; Davies, Mary-Ann; Duda, Stephany N.; Malateste, Karen; Nash, Denis; Wools-Kaloustian, Kara; von Groote, Per M.; Egger, Matthias; Biostatistics, School of Public HealthPurpose: The objectives of the International epidemiology databases to evaluate AIDS (IeDEA) are to (i) evaluate the delivery of combination antiretroviral therapy (ART) in children, adolescents and adults in sub-Saharan Africa, (ii) to describe ART regimen effectiveness, durability and tolerability, (iii) to examine HIV-related comorbidities and coinfections and (iv) to examine the pregnancy-related and HIV-related outcomes of women on ART and their infants exposed to HIV or ART in utero or via breast milk. Participants: IeDEA is organised in four regions (Central, East, Southern and West Africa), with 240 treatment and care sites, six data centres at African, European and US universities, and almost 1.4 million children, adolescents and adult people living with HIV (PLWHIV) enrolled. Findings to date: The data include socio-demographic characteristics, clinical outcomes, opportunistic events, treatment regimens, clinic visits and laboratory measurements. They have been used to analyse outcomes in PLWHIV-1 or PLWHIV-2 who initiate ART, including determinants of mortality, of switching to second-line and third-line ART, drug resistance, loss to follow-up and the immunological and virological response to different ART regimens. Programme-level estimates of mortality have been corrected for loss to follow-up. We examined the impact of coinfection with hepatitis B and C, and the epidemiology of different cancers and of (multidrug resistant) tuberculosis, renal disease and of mental illness. The adoption of 'Treat All', making ART available to all PLWHIV regardless of CD4+ cell count or clinical stage was another important research topic. Future plans: IeDEA has formulated several research priorities for the 'Treat All' era in sub-Saharan Africa. It recently obtained funding to set up sentinel sites where additional data are prospectively collected on cardiometabolic risks factors as well as mental health and liver diseases, and is planning to create a drug resistance database.Item Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi’s sarcoma in five countries across sub-Saharan Africa.(BMC, 2016) Freeman, Esther; Semeere, Aggrey; Wenger, Megan; Bwana, Mwebesa; Asirwa, F. Chite; Busakhala, Naftali; Oga, Emmanuel; Jedy-Agba, Elima; Kwaghe, Vivian; Iregbu, Kenneth; Jaquet, Antoine; Dabis, Francois; Yumo, Habakkuk Azinyui; Dusingize, Jean Claude; Bangsberg, David; Anastos, Kathryn; Phiri, Sam; Bohlius, Julia; Egger, Matthias; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Martin, Jeffrey; Department of Biostatistics, Fairbanks School of Public HealthSurvival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data.