Browsing by Author "Fox MP"
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Item Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.(2023-Dec-19) Trickey A; Johnson LF; Fung F; Bonifacio R; Iwuji C; Biraro S; Bosomprah S; Chirimuta L; Euvrard J; Fatti G; Fox MP; Von Groote P; Gumulira J; Howard G; Jennings L; Kiragga A; Muula G; Tanser F; Wagener T; Low A; Vickerman P; Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.; Department of Civil Engineering, University of Bristol, Bristol, UK.; Desmond Tutu Health Foundation, Institute of Infectious Diseases and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.; Kheth'Impilo AIDS Free Living, Cape Town, South Africa.; NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol, Bristol, UK.; UK Meteorological Office, Exeter, UK.; Newlands Clinic, Harare, Zimbabwe.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Lighthouse Trust, Mzimba, Malawi.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Institute of Environmental Science and Geography, University of Potsdam, Potsdam, Germany.; Department of Civil Engineering and Cabot Institute of the Environment, University of Bristol, Bristol, UK.; Climate and Earth Observation Unit, Research Assessment and Monitoring Division, World Food Programme HQ, Rome, Italy.; Research Division, African Population and Health Research Center, Nairobi, Kenya.; Population Health Sciences, University of Bristol, Bristol, UK. adam.trickey@bristol.ac.uk.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Global Health Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Africa Health Research Institute, KwaZulu-Natal, South Africa.; ICAP at Columbia University, Nakasero, Kampala, Uganda.; School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; Department of Global Health and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.; Population Health Sciences, University of Bristol, Bristol, UK.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.Item 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.Item Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.(2020-Jan) Tsondai PR; Sohn AH; Phiri S; Sikombe K; Sawry S; Chimbetete C; Fatti G; Hobbins MA; Technau KG; Rabie H; Bernheimer J; Fox MP; Judd A; Collins IJ; Davies MA; Newlands Clinic, Harare, Zimbabwe.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; MRC Clinical Trials Unit at UCL, University College London (UCL), London, United Kingdom.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; SolidarMed, Luzern, Switzerland.; Department of Paediatrics and Child Health, Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa.; Harriet Shezi Children's Clinic, Wits Reproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.; Médecins Sans Frontiers, Khayelitsha, South Africa.; Kheth'Impilo, Cape Town, South Africa.; Department of Global Health and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.Item Extending Visit Intervals for Clinically Stable Patients on Antiretroviral Therapy: Multicohort Analysis of HIV Programs in Southern Africa.(2019-Aug-01) Haas AD; Johnson LF; Grimsrud A; Ford N; Mugglin C; Fox MP; Euvrard J; van Lettow M; Prozesky H; Sikazwe I; Chimbetete C; Hobbins M; Kunzekwenyika C; Egger M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; 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.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Global Health, Boston University School of Public Health, Boston, MA.; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Newlands Clinic, Harare, Zimbabwe.; Department of HIV/AIDS World Health Organization, Geneva, Switzerland.; SolidarMed, Masvingo, Zimbabwe.; International AIDS Society, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.; Dignitas International, Zomba, Malawi.; SolidarMed, Lucerne, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS: We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load <1000 copies/mL), immunological (CD4 >200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS: We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION: Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.Item 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.Item 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.Item Retention and mortality on antiretroviral therapy in sub-Saharan Africa: collaborative analyses of HIV treatment programmes.(2018-Feb) Haas AD; Zaniewski E; Anderegg N; Ford N; Fox MP; Vinikoor M; Dabis F; Nash D; Sinayobye JD; Niyongabo T; Tanon A; Poda A; Adedimeji AA; Edmonds A; Davies MA; Egger M; Institut Supérieur des Sciences de la santé, Université Polytechnique de Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.; Department of Epidemiology and Biostatistics, City University of New York, School of Public Health, New York, NY, USA.; Institute for Implementation Science in Population Health, City University of New York, New York, NY, USA.; Department of Epidemiology and Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; ISPED, Centre Inserm U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.; Department of Global Health, Boston University School of Public Health, Boston, MA, USA.; 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.; World Health Organisation, Geneva, Switzerland.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Rwanda Military Hospital, Kigali, Rwanda.; Service de Maladies Infectieuses et Tropicales (SMIT), CHU de Treichville, Abidjan, Cote d'Ivoire.; Centre National de Reference en Matiere de VIH/SIDA (CNR), Bujumbura, Burundi.; School of Medicine, University of Zambia, Lusaka, Zambia.; Institute of Social & Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: By 2020, 90% of all people diagnosed with HIV should receive long-term combination antiretroviral therapy (ART). In sub-Saharan Africa, this target is threatened by loss to follow-up in ART programmes. The proportion of people retained on ART long-term cannot be easily determined, because individuals classified as lost to follow-up, may have self-transferred to another HIV treatment programme, or may have died. We describe retention on ART in sub-Saharan Africa, first based on observed data as recorded in the clinic databases, and second adjusted for undocumented deaths and self-transfers. METHODS: We analysed data from HIV-infected adults and children initiating ART between 2009 and 2014 at a sub-Saharan African HIV treatment programme participating in the International epidemiology Databases to Evaluate AIDS (IeDEA). We used the Kaplan-Meier method to calculate the cumulative incidence of retention on ART and the Aalen-Johansen method to calculate the cumulative incidences of death, loss to follow-up, and stopping ART. We used inverse probability weighting to adjust clinic data for undocumented mortality and self-transfer, based on estimates from a recent systematic review and meta-analysis. RESULTS: We included 505,634 patients: 12,848 (2.5%) from Central Africa, 109,233 (21.6%) from East Africa, 347,343 (68.7%) from Southern Africa and 36,210 (7.2%) from West Africa. In crude analyses of observed clinic data, 52.1% of patients were retained on ART, 41.8% were lost to follow-up and 6.0% had died 5 years after ART initiation. After accounting for undocumented deaths and self-transfers, we estimated that 66.6% of patients were retained on ART, 18.8% had stopped ART and 14.7% had died at 5 years. CONCLUSIONS: Improving long-term retention on ART will be crucial to attaining the 90% on ART target. Naïve analyses of HIV cohort studies, which do not account for undocumented mortality and self-transfer of patients, may severely underestimate both mortality and retention on ART.Item 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.Item 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.Item Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.(2022-Jan-29) Ballif M; Christ B; Anderegg N; Chammartin F; Muhairwe J; Jefferys L; Hector J; van Dijk J; Vinikoor MJ; van Lettow M; Chimbetete C; Phiri SJ; Onoya D; Fox MP; Egger M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; SolidarMed, Maseru, Lesotho.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.; SolidarMed, Pemba, Mozambique.; SolidarMed, Masvingo, Zimbabwe.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South Africa.; Dignitas International, Zomba, Malawi.; Department of Epidemiology and Global Health, Boston University School of Public Health, Boston, Massachusetts, USA.; Centre for Infectious Disease Research and Epidemiology, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa. METHODS: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. RESULTS: Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. CONCLUSIONS: Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU.Item 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.