Browsing by Author "Giddy J"

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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.
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.
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.