Browsing by Author "Wood R"

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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.
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.
Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.
(2014-Nov) Ballif M; Nhandu V; Wood R; Dusingize JC; Carter EJ; Cortes CP; McGowan CC; Diero L; Graber C; Renner L; Hawerlander D; Kiertiburanakul S; Du QT; Sterling TR; Egger M; Fenner L; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre Intégré de Recherches Biocliniques, Abidjan, Côte d'Ivoire.; United States Agency for International Development Academic Model Providing Access to Healthcare, Eldoret, Kenya.; Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.; Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Children's Hospital, Ho Chi Minh City, Viet Nam.; Women's Equity in Access to Care & Treatment, Kigali, Rwanda.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; University of Ghana Medical School, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Chile School of Medicine, Santiago, Chile.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.
Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.
(2023-Jun) Broger T; Koeppel L; Huerga H; Miller P; Gupta-Wright A; Blanc FX; Esmail A; Reeve BWP; Floridia M; Kerkhoff AD; Ciccacci F; Kasaro MP; Thit SS; Bastard M; Ferlazzo G; Yoon C; Van Hoving DJ; Sossen B; García JI; Cummings MJ; Wake RM; Hanson J; Cattamanchi A; Meintjes G; Maartens G; Wood R; Theron G; Dheda K; Olaru ID; Denkinger CM; Population Health Program, Tuberculosis Group, Texas Biomedical Research Institute, San Antonio, TX, USA.; National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA; Trauma Center, University of California San Francisco, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Division of Emergency Medicine, University of Cape Town, Cape Town, South Africa; Division of Emergency Medicine, Stellenbosch University, Cape Town, South Africa.; The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK; Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; South African MRC Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.; Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, USA; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany.; New Zealand Institute for Plant and Food Research, Auckland, New Zealand.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; UniCamillus, International University of Health and Medical Science, Rome, Italy; Community of Sant'Egidio, DREAM programme, Rome, Italy.; Field Epidemiology Department, Epicentre, Paris, France.; Department of Medicine, Médecins Sans Frontières, Paris, France.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; South African MRC Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; UNC Global Projects, LLC Zambia, Lusaka, Zambia.; Institute for Global Health, University College London, London, UK; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases, Johannesburg, South Africa; Institute for Infection and Immunity, St George's University of London, London, UK.; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Department of Medicine, University of Medicine 2, Yangon, Myanmar.; Service de Pneumologie, l'institut du thorax, Nantes Université, CHU Nantes, Nantes, France.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; German Center for Infection Research, partner site, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: claudia.denkinger@uni-heidelberg.de.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.
Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.
(2022-Apr-01) Davies C; Johnson L; Sawry S; Chimbetete C; Eley B; Vinikoor M; Technau KG; Ehmer J; Rabie H; Phiri S; Tanser F; Malisita K; Fatti G; Osler M; Wood R; Newton S; Haas A; Davies MA; Newlands Clinic, Harare, Zimbabwe.; Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town.; School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Paediatrics and Child Health, Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa.; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.; Institute of Social and Preventive Medicine, University of Bern, Switzerland.; Queen Elizabeth Central Hospital, Blantyre, Malawi.; Kheth'Impilo AIDS Free Living.; Division of Epidemiology and Biostatistics, Department of Global Health, Stellenbosch University.; Gugulethu HIV Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; SolidarMed, Lucerne, Switzerland.; Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malaysia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.
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.
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.
Outcomes of Infants Starting Antiretroviral Therapy in Southern Africa, 2004-2012.
(2015-Aug-15) Porter M; Davies MA; Mapani MK; Rabie H; Phiri S; Nuttall J; Fairlie L; Technau KG; Stinson K; Wood R; Wellington M; Haas AD; Giddy J; Tanser F; Eley B; *School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †MMed Paeds and Child Health (UNZA), Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; ‡Tygerberg Academic Hospital and Stellenbosch University, Cape Town, South Africa; §Lighthouse Trust Clinic, Lilongwe, Malawi; ‖Red Cross War Memorial Children's Hospital, Cape Town, South Africa; ¶School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; #Wits Reproductive Health and HIV Institute (Wits RHI), University of the Witwatersrand, Johannesburg, South Africa; **Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa; ††Médecins Sans Frontierès, Khayelitsha and School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; ‡‡Gugulethu Community Health Centre and Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; §§Newlands Clinic, Harare, Zimbabwe; ‖‖Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; ¶¶McCord Hospital, Durban, South Africa; and ##Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: There are limited published data on the outcomes of infants starting antiretroviral therapy (ART) in routine care in Southern Africa. This study aimed to examine the baseline characteristics and outcomes of infants initiating ART. METHODS: We analyzed prospectively collected cohort data from routine ART initiation in infants from 11 cohorts contributing to the International Epidemiologic Database to Evaluate AIDS in Southern Africa. We included ART-naive HIV-infected infants aged <12 months initiating ≥3 antiretroviral drugs between 2004 and 2012. Kaplan-Meier estimates were calculated for mortality, loss to follow-up (LTFU), transfer out, and virological suppression. We used Cox proportional hazard models stratified by cohort to determine baseline characteristics associated with outcomes mortality and virological suppression. RESULTS: The median (interquartile range) age at ART initiation of 4945 infants was 5.9 months (3.7-8.7) with follow-up of 11.2 months (2.8-20.0). At ART initiation, 77% had WHO clinical stage 3 or 4 disease and 87% were severely immunosuppressed. Three-year mortality probability was 16% and LTFU 29%. Severe immunosuppression, WHO stage 3 or 4, anemia, being severely underweight, and initiation of treatment before 2010 were associated with higher mortality. At 12 months after ART initiation, 17% of infants were severely immunosuppressed and the probability of attaining virological suppression was 56%. CONCLUSIONS: Most infants initiating ART in Southern Africa had severe disease with high probability of LTFU and mortality on ART. Although the majority of infants remaining in care showed immune recovery and virological suppression, these responses were suboptimal.
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.
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.
Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.
(2020-Jul) Zaniewski E; Dao Ostinelli CH; Chammartin F; Maxwell N; Davies MA; Euvrard J; van Dijk J; Bosomprah S; Phiri S; Tanser F; Sipambo N; Muhairwe J; Fatti G; Prozesky H; Wood R; Ford N; Fox MP; Egger M; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Department of Global Health, Boston University, Boston, MA, USA.; Kheth'Impilo AIDS Free Living, Cape Town, South Africa.; Lighthouse, Lilongwe, Malawi.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; SolidarMed, Masvingo, Zimbabwe.; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.; SolidarMed, Maseru, Lesotho.; Department of Epidemiology, Boston University, Boston, MA, USA.; Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.; Gugulethu ART Programme (Desmond Tutu HIV Centre), Cape Town, South Africa.; Lincoln International Institute for Rural Health, University of Lincoln, Lincoln, United Kingdom.; Division of Infectious Diseases, Department of Medicine, Stellenbosch University, Cape Town, South Africa.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Department of HIV/AIDS and Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.; Africa Health Research Institute, KwaZulu-Natal, 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.; School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm RESULTS: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.