Browsing by Author "Boulle A"

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    Brief Report: Assessing the Association Between Changing NRTIs When Initiating Second-Line ART and Treatment Outcomes.
    (2018-Apr-01) Rohr JK; Ive P; Horsburgh CR; Berhanu R; Hoffmann CJ; Wood R; Boulle A; Giddy J; Prozesky H; Vinikoor M; Mwanza MW; Wandeler G; Davies MA; Fox MP; School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Epidemiology, Boston University School of Public Health, Boston, MA.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, Department of Internal Medicine, Helen Joseph Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston, MA.; McCord Hospital, Durban, South Africa.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.; The Aurum Institute, Johannesburg, South Africa.; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Center for Global Health and Development, Boston University, Boston, MA.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa.; Department of Medicine, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: After first-line antiretroviral therapy failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is uncertain due to the high potency of protease inhibitors used in second line. SETTING: We used clinical data from 6290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa cohort. METHODS: We included patients who initiated on standard first-line antiretroviral therapy and had evidence of first-line failure. We used propensity score-adjusted Cox proportional-hazards models to evaluate the impact of change in NRTI on second-line failure compared with remaining on the same NRTI in second line. In South Africa, where viral load monitoring was available, treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In Zambia, it was defined as 2 consecutive CD4 counts <100 cells/mm. RESULTS: Among patients in South Africa initiated on zidovudine (AZT), the adjusted hazard ratio for second-line virologic failure was 0.25 (95% confidence interval: 0.11 to 0.57) for those switching to tenofovir (TDF) vs. remaining on AZT. Among patients in South Africa initiated on TDF, switching to AZT in second line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% confidence interval: 0.13 to 0.96]). In Zambia, where viral load monitoring was not available, results were less conclusive. CONCLUSIONS: Changing NRTI in second line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on TDF or with contraindications to specific NRTIs is needed.
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    Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.
    (2020-Dec-01) Tsondai PR; Braithwaite K; Fatti G; Bolton Moore C; Chimbetete C; Rabie H; Phiri S; Sawry S; Eley B; Hobbins MA; Boulle A; Taghavi K; Sohn AH; Davies MA; Newlands Clinic, Harare, Zimbabwe.; Harriet Shezi Children's Clinic, Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Kheth' Impilo, AIDS Free Living, Cape Town.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; Department of Medicine, University of Alabama at Birmingham, Alabama, USA.; Department of Pediatrics and Child Health, Tygerberg Hospital, Stellenbosch University, Parow, South Africa.; Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town.; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.; Research & Quality Unit, SolidarMed, Lucerne.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). METHODS: We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. RESULTS: Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). CONCLUSION: Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.
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    Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.
    (2024-Aug) Nyakato P; Schomaker M; Boulle A; Euvrard J; Wood R; Eley B; Prozesky H; Christ B; Anderegg N; Ayakaka I; Rafael I; Kunzekwenyika C; Moore CB; van Lettow M; Chimbetete C; Mbewe S; Ballif M; Egger M; Yiannoutsos CT; Cornell M; Davies MA; R.M Fairbanks, School of Public Health, Department of Biostatistics, Indiana University, Indianapolis, Indiana, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; SolidarMed, Pemba, Mozambique.; Centre for Infectious Disease Epidemiology and Research, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; SolidarMed, Masvingo, Zimbabwe.; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa.; Lighthouse Trust Clinic, Lilongwe, Malawi.; SolidarMed, Maseru, Lesotho.; Khayelitsha ART Programme, Cape Town, South Africa.; Western Cape Government: Health and Wellness, Cape Town, South Africa.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Madiro, Toronto, Canada.; Department of Statistics, Ludwig-Maximilians-Universität München, Munich, Germany.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Gugulethu HIV Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Dignitas International, Zomba, Malawi.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.
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    Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia.
    (2022-Jan-10) Nyemba DC; Kalk E; Vinikoor MJ; Madlala HP; Mubiana-Mbewe M; Mzumara M; Moore CB; Slogrove AL; Boulle A; Davies MA; Myer L; Powis K; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. dorothy.nyemba@uct.ac.za.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Ukwanda Centre for Rural Health, Faculty of Medicine & Health Sciences, Stellenbosch University, Worcester, South Africa.; Department of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Western Cape Government: Health, Cape Town, South Africa.; Division of Epidemiology & Biostatistics, Faculty of Health Sciences, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa. dorothy.nyemba@uct.ac.za.; Department of Paediatrics & Child Health, Faculty of Medicine & Health Sciences, Stellenbosch University, Worcester, South Africa.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Epidemiology & Biostatistics, Faculty of Health Sciences, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. METHODS: We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6-10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. RESULTS: Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6-10 weeks were lower among infants who were HEU vs HU [β = - 0.29 (95% CI: - 0.46, - 0.12) and [β = - 0.42 (95% CI: - 0.68, - 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = - 0.28 CI: - 0.50, - 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6-10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = - 0.30 CI: - 0.59, - 0.01)] at 6 months, without other anthropometric differences at either site. CONCLUSION: Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.
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    Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.
    (2015-Nov-01) Koller M; Fatti G; Chi BH; Keiser O; Hoffmann CJ; Wood R; Prozesky H; Stinson K; Giddy J; Mutevedzi P; Fox MP; Law M; Boulle A; Egger M; *Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †Kheth'Impilo, Cape Town, South Africa; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Aurum Institute for Health Research, Johannesburg, South Africa; ‖Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ¶Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; #Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; **Sinikithemba Clinic, McCord Hospital, Durban, South Africa; ††Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; ‡‡Health Economics and Epidemiology Research Office, University of the Witwatersrand, Johannesburg, South Africa; §§Center for Global Health & Development and Department of Epidemiology, Boston University, Boston, MA; ‖‖Biostatistics and Databases Program, The Kirby Institute, Faculty of Medicine, The University of New South Wales, Sydney, Australia; and ¶¶Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS: We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS: In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS: CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.
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    Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia.
    (2018-Sep-01) Brennan AT; Bor J; Davies MA; Wandeler G; Prozesky H; Fatti G; Wood R; Stinson K; Tanser F; Bärnighausen T; Boulle A; Sikazwe I; Zanolini A; Fox MP; Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Research Department of Infection and Population Health, University College London, London, United Kingdom.; Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa.; Division of Public Health Medicine, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Institute of Public Health, School of Medicine, Heidelberg University, Heidelberg, Germany.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Department of Global Health, School of Public Health, Boston University, Boston, Massachusetts.; Kheth'Impilo AIDS Free Living, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.; Africa Health Research Institute, Durban, South Africa.; The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)-infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = -15 percentage points, 95% CI: -18, -12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = -1.8% (95% CI: -3.5, -0.1); complier relative risk = 0.74) but not in South Africa (RD = -0.9% (95% CI: -5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts.
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    Monitoring effectiveness of programmes to prevent mother-to-child HIV transmission in lower-income countries.
    (2008-Jan) Stringer EM; Chi BH; Chintu N; Creek TL; Ekouevi DK; Coetzee D; Tih P; Boulle A; Dabis F; Shaffer N; Wilfert CM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eli@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Ambitious goals for paediatric AIDS control have been set by various international bodies, including a 50% reduction in new paediatric infections by 2010. While these goals are clearly appropriate in their scope, the lack of clarity and consensus around how to monitor the effectiveness of programmes to prevent mother-to-child HIV transmission (PMTCT) makes it difficult for policy-makers to mount a coordinated response. In this paper, we develop the case for using population HIV-free child survival as a gold standard metric to measure the effectiveness of PMTCT programmes, and go on to consider multiple study designs and source populations. Finally, we propose a novel community survey-based approach that could be implemented widely throughout the developing world with minor modifications to ongoing Demographic and Health Surveys.
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    Prognosis of children with HIV-1 infection starting antiretroviral therapy in Southern Africa: a collaborative analysis of treatment programs.
    (2014-Jun) Davies MA; May M; Bolton-Moore C; Chimbetete C; Eley B; Garone D; Giddy J; Moultrie H; Ndirangu J; Phiri S; Rabie H; Technau KG; Wood R; Boulle A; Egger M; Keiser O; From the *School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §University of North Carolina, Chapel Hill, NC; ¶Newlands clinic, Harare, Zimbabwe; ‖Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town; **Médecins Sans Frontières (MSF) South Africa and Khayelitsha ART Programme, Cape Town; ††Sinikithemba Clinic, McCord Hospital, Durban; ‡‡Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg; §§Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Soweto; ¶¶Africa Centre for Health and Population Studies, University of Kwazulu-Natal, Somkhele, South Africa; ‖‖Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi and Liverpool School of Tropical Medicine, Liverpool, United Kingdom; ***Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch; †††Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, and University of the Witwatersrand, Johannesburg; ‡‡‡Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; and §§§Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 2010. Children lost to follow up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5-2.3] in children 5-10 years with CD4% ≥10%, World Health Organization stage I/II, WAZ ≥ -2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% < 5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics = 0.753 and 0.745 for models with and without CD4%, respectively). CONCLUSIONS: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
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    Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa: analysis of cohort studies at antiretroviral treatment programmes.
    (2018-Jan-11) Ballif M; Zürcher K; Reid SE; Boulle A; Fox MP; Prozesky HW; Chimbetete C; Zwahlen M; Egger M; Fenner L; Newlands Clinic, Harare, Zimbabwe.; Department of Internal Medicine, Health Economics and Epidemiology Research Office, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Division of Infection Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Centre for Infectious Disease Epidemiology and Research (CIDER), School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town, South Africa.; Departments of Epidemiology and Global Health, Boston University, Boston, USA.; Institute of Social and Preventive Medicine, University of Bern, Bern, BE, Switzerland.; Médecins Sans Frontières, Khayelitsha, South Africa.; Tuberculosis Department Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.
    OBJECTIVES: Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa. SETTING: Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe. PARTICIPANTS: We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014. PRIMARY OUTCOME MEASURE: We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses. RESULTS: All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in December, followed by April-May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year. CONCLUSIONS: Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors.
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    Temporal trends in the characteristics of children at antiretroviral therapy initiation in southern Africa: the IeDEA-SA Collaboration.
    (2013) Davies MA; Phiri S; Wood R; Wellington M; Cox V; Bolton-Moore C; Timmerman V; Moultrie H; Ndirangu J; Rabie H; Technau K; Giddy J; Maxwell N; Boulle A; Keiser O; Egger M; Eley B; Newlands Clinic, Harare, Zimbabwe.; Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa.; Wits Reproductive Health and HIV Institute, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Faculty of Health Sciences, University of Witwatersrand, Soweto, Johannesburg, South Africa.; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.; Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital and University of Witwatersrand, Johannesburg, South Africa.; Knowledge Translation Unit, University of Cape Town Lung Institute, Cape Town, South Africa.; Médecins Sans Frontières South Africa and Khayelitsha ART Programme, Khayelitsha, Cape Town, South Africa.; Sinikithemba Clinic, McCord Hospital, Durban, South Africa.; Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi.; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.; Gugulethu Community Health Centre and Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. METHODOLOGY/PRINCIPAL FINDINGS: Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. CONCLUSIONS/SIGNIFICANCE: Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.
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    The revolving door of HIV care: Revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals.
    (2021-May) Ehrenkranz P; Rosen S; Boulle A; Eaton JW; Ford N; Fox MP; Grimsrud A; Rice BD; Sikazwe I; Holmes CB; Center for Innovation in Global Health, Georgetown University, Washington, DC, United States of America.; MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.; Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; HIV & Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.; Department of Public Health, Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, United Kingdom.; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; HIV Programmes & Advocacy Department, International AIDS Society, Cape Town, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Global Health, Boston University School of Public Health, Boston, MA, United States of America.; Global Health, Bill & Melinda Gates Foundation, Seattle, WA, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.