Browsing by Author "Theron G"

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Association of Maternal Viral Load and CD4 Count With Perinatal HIV-1 Transmission Risk During Breastfeeding in the PROMISE Postpartum Component.
(2021-Oct-01) Flynn PM; Taha TE; Cababasay M; Butler K; Fowler MG; Mofenson LM; Owor M; Fiscus S; Stranix-Chibanda L; Coutsoudis A; Gnanashanmugam D; Chakhtoura N; McCarthy K; Frenkel L; Beck I; Mukuzunga C; Makanani B; Moodley D; Nematadzira T; Kusakara B; Patil S; Vhembo T; Bobat R; Mmbaga BT; Masenya M; Nyati M; Theron G; Mulenga H; Shapiro DE; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi.; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA.; Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.; Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD.; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.; Maternal and Pediatric Infectious Disease Branch, Division of Extramural Research, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.; Department of Obstetrics and Gynaecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.; University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.; Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi.; Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa.; Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe.; Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India.; Department of Pediatrics and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA.; Department of Pediatrics, Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.; Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. METHODS: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. CONCLUSIONS: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection.
Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.
(2024-Jul) Broger T; Marx FM; Theron G; Marais BJ; Nicol MP; Kerkhoff AD; Nathavitharana R; Huerga H; Gupta-Wright A; Kohli M; Nichols BE; Muyoyeta M; Meintjes G; Ruhwald M; Peeling RW; Pai NP; Pollock NR; Pai M; Cattamanchi A; Dowdy DW; Dewan P; Denkinger CM; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Boston Children's Hospital, Boston, MA, USA.; The University of Sydney Infectious Diseases Institute, Sydney, NSW, Australia; Children's Hospital at Westmead, Sydney, NSW, Australia.; Bill & Melinda Gates Foundation, Seattle, WA, USA.; Department of Epidemiology, Epicentre, Paris, France.; McGill International TB Centre, McGill University, Montreal, QC, Canada.; 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 Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.; London School of Hygiene & Tropical Medicine, London, UK.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; German Center for Infection Research, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: claudia.denkinger@uni-heidelberg.de.; Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Division of HIV, Infectious Diseases, and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.; Department of Medicine, Centre for Outcomes Research & Evaluation, McGill University, Montreal, QC, Canada.; FIND, Geneva, Switzerland.; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.
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 on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial.
(2021) Stranix-Chibanda L; Tierney C; Pinilla M; George K; Aizire J; Chipoka G; Mallewa M; Naidoo M; Nematadzira T; Kusakara B; Violari A; Mbengeranwa T; Njau B; Fairlie L; Theron G; Mubiana-Mbewe M; Khadse S; Browning R; Fowler MG; Siberry GK; FHI 360, Durham, NC, United States of America.; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.; University of North Carolina Project, Lilongwe, Malawi.; Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.; University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.; Office of HIV/AIDS, United States Agency for International Development, Washington, DC, United States of America.; Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research in the Department of Biostatistics, Boston, MA, United States of America.; Department of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa.; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa.; Perinatal HIV Research Unit, Johannesburg, South Africa.; Makerere University-Johns Hopkins University Research Programme, Kampala, Uganda.; University of KwaZulu-Natal, Centre Aids Prevention Research South Africa (CAPRISA), Durban, South Africa.; College of Medicine-Johns Hopkins University Project, Blantyre, Malawi.; University of Zimbabwe Faculty of Medicine and Health Sciences, Child and Adolescent Health Unit, Harare, Zimbabwe.; Department of Obstetrics and Gynaecology, BJ Government Medical College, Pune, India.; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States of America.; Kilimanjaro Christian Medical Center, Moshi, United Republic of Tanzania.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Malnutrition is highly prevalent in HIV-exposed perinatally uninfected infants (HEUs) increasing the risk of morbidity and mortality throughout the life course. We set out to compare the effect of postnatal exposure to maternal antiretroviral therapy (mART) in breastmilk versus infant Nevirapine prophylaxis (iNVP) on somatic growth of HEUs in the randomized PROMISE trial. METHODS AND FINDINGS: We randomized 2431 mothers with HIV and their 2444 HEUs from six African countries and India 6-14 days after delivery to mART or iNVP for prevention of breastmilk HIV transmission. The mART regimen contained tenofovir/emtricitabine (99%) plus lopinavir/ritonavir. Infant growth parameters were compared at postnatal week 10, 26, 74 and 104 using World Health Organization (WHO) z-scores for length-for-age (LAZ), weight-for-age (WAZ), and head circumference-for-age (HCAZ). Week 26 LAZ was the primary endpoint measure. Student T-tests compared mean LAZ, WAZ, and HCAZ; estimated mean and 95% confidence interval (CI) are presented. Maternal and infant baseline characteristics were comparable between study arms. The estimated median breastfeeding duration was 70 weeks. After a mean follow-up of 88 weeks, mean LAZ and WAZ were below the WHO reference population mean at all timepoints, whereas mean HCAZ was not. The mART and iNVP arms did not differ for the primary outcome measure of LAZ at week 26 (p-value = 0.39; estimated mean difference (95%CI) of -0.05 (-0.18, 0.07)) or any of the other secondary growth outcome measures or timepoints (all p-values≥0.16). Secondary analyses of the primary outcome measure adjusting for week 0 LAZ and other covariates did not change these results (all p-values≥0.09). However, infants assigned to mART were more likely to have stunting compared to iNVP infants at week 26 (odds ratio (95% CI): 1.28 (1.05, 1.57)). CONCLUSIONS: In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head circumference with no clinically relevant differences between the groups. Despite breastfeeding into the second year of life, length and weight were below reference population means at all ages in both arms. Further investment is needed to optimize postnatal growth of infants born to women with HIV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT01061151.
Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.
(2024-Jul-15) Dadabhai S; Chou VB; Pinilla M; Chinula L; Owor M; Violari A; Moodley D; Stranix-Chibanda L; Matubu TA; Chareka GT; Theron G; Kinikar AA; Mubiana-Mbewe M; Fairlie L; Bobat R; Mmbaga BT; Flynn PM; Taha TE; McCarthy KS; Browning R; Mofenson LM; Brummel SS; Fowler MG; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Soweto.; Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; National Institute of Allergy and Infectious Diseases/NIH, Rockville, MD.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Global Women's Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; St. Jude Children's Research Hospital, Memphis, TN.; B.J. Government Medical College, Department of Paediatrics, Pune, India.; Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA.; MU-JHU Research Collaboration; Upper Mulago Hill Road, Kampala, Uganda.; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA.; Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg.; University of North Carolina Project Malawi, Tidziwe Centre, Lilongwe, Malawi.; Centre for Infectious Disease Research in Zambia, George CRS, Lusaka, Zambia.; Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, University of KwaZulu Natal, Congella, South Africa.; Kamuzu University of Health Sciences-Johns Hopkins Research Project, Blantyre, Malawi.; Child, Adolescent and Women's Health Department, Faculty of Medicine and Health Sciences, University of Zimbabwe, Avondale.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.; Kilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute and Kilimanjaro Christian Medical University College/Kilimanjaro CRS, Moshi, Tanzania.; University of Zimbabwe Clinical Trials Research Centre, Belgravia, Harare, Zimbabwe.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.
Placing the values and preferences of people most affected by TB at the center of screening and testing: an approach for reaching the unreached.
(2023) Kerkhoff AD; West NS; Del Mar Castro M; Branigan D; Christopher DJ; Denkinger CM; Nhung NV; Theron G; Worodria W; Yu C; Muyoyeta M; Cattamanchi A; Treatment Action Group, New York, NY, USA.; World Alliance for Lung and Intensive Care in Uganda, Kampala, Uganda.; Division of Infectious Diseases and Tropical Medicine, Center of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; German Center of Infection Research, Partner Site Heidelberg University Hospital, Heidelberg, Germany.; Center for Tuberculosis Research, De La Salle Medical and Health Sciences Institute, City of Dasmarinas, The Philippines.; Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA.; Division of Pulmonology, Mulago National Referral Hospital, Kampala, Uganda.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA.; Pulmonary, Critical Care Allergy and Sleep Medicine, University of California San Francisco, San Francisco, USA.; University of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Department of Pulmonary Medicine, Christian Medical College, Vellore, India.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people
Prevention of HIV-1 Transmission Through Breastfeeding: Efficacy and Safety of Maternal Antiretroviral Therapy Versus Infant Nevirapine Prophylaxis for Duration of Breastfeeding in HIV-1-Infected Women With High CD4 Cell Count (IMPAACT PROMISE): A Randomized, Open-Label, Clinical Trial.
(2018-Apr-01) Flynn PM; Taha TE; Cababasay M; Fowler MG; Mofenson LM; Owor M; Fiscus S; Stranix-Chibanda L; Coutsoudis A; Gnanashanmugam D; Chakhtoura N; McCarthy K; Mukuzunga C; Makanani B; Moodley D; Nematadzira T; Kusakara B; Patil S; Vhembo T; Bobat R; Mmbaga BT; Masenya M; Nyati M; Theron G; Mulenga H; Butler K; Shapiro DE; Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.; Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.; Department of Pediatrics, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.; Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.; Elisabeth Glaser Pediatric AIDS Foundation, Washington, DC.; Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi.; Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa.; University of Zimbabwe-University of California, San Francisco, Harare, Zimbabwe.; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA.; Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India.; Department of Obstetrics and Gynecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.; University of North Carolina-Lilongwe, Lilongwe, Malawi.; Department of Paediatrics and Child Health, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.; Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; George Clinic, Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child transmission throughout the breastfeeding period. SETTING: Fourteen sites in Sub-Saharan Africa and India. METHODS: A randomized, open-label strategy trial was conducted in HIV-1-infected women with CD4 counts ≥350 cells/mm (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1-uninfected newborns. Randomization at 6-14 days postpartum was to mART or infant nevirapine (iNVP) prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother-infant pairs except those with infant HIV-1 infection at entry. RESULTS: Between June 2011 and October 2014, 2431 mother-infant pairs were enrolled; 97% of women were World Health Organization Clinical Stage I, median screening CD4 count 686 cells/mm. Median infant gestational age/birth weight was 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and 7 of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio 1.0, 96% repeated confidence interval 0.3-3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening, or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively). CONCLUSIONS: Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1-free survival at 24 months.
Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.
(2019-Sep) Stranix-Chibanda L; Brummel S; Pilotto J; Mutambanengwe M; Chanaiwa V; Mhembere T; Kamateeka M; Aizire J; Masheto G; Chamanga R; Maluwa M; Hanley S; Joao E; Theron G; Nevrekar N; Nyati M; Santos B; Aurpibul L; Mubiana-Mbewe M; Oliveira R; Anekthananon T; Mlay P; Angelidou K; Tierney C; Ziemba L; Coletti A; McCarthy K; Basar M; Chakhtoura N; Browning R; Currier J; Fowler MG; Flynn P; Instituto of Pediatrics Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Harvard T.H. Chan School of Public Health, Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Centre Aids Prevention Research South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, USA.; University of Zimbabwe College of Health Sciences, Paediatrics and Child Health, Harare, Zimbabwe. lstranix@uzchs-ctrc.org.; College of Medicine - Johns Hopkins Research Project, Blantyre, Malawi.; University of North Carolina Project, Lilongwe, Malawi.; University of Zimbabwe College of Health Sciences - Clinical Trials Research Centre, 15 Phillips Avenue, Belgravia, Harare, Zimbabwe.; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.; Perinatal HIV Research Unit, Johannesburg, South Africa.; Division of Infectious Diseases, University of California Los Angeles, Los Angeles, USA.; Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research in the Department of Biostatistics, Boston, USA.; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, USA.; Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Department of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa.; FHI 360, IMPAACT Operations Center, Durham, NC, USA.; University of Zimbabwe College of Health Sciences - Clinical Trials Research Centre, 15 Phillips Avenue, Belgravia, Harare, Zimbabwe. lstranix@uzchs-ctrc.org.; Frontier Science and Technology Research Foundation, Amherst, USA.; Department of Infectious Diseases, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, USA.; Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, China.; Hospital Nossa Senhora da Conceicao, Porto Alegre, Brazil.; Laboratorio de AIDS e Imunologia Molecular - Fiocruz, Hospital Geral de Nova Iguacu, Rio de Janeiro, Brazil.; Makerere University - Johns Hopkins University Research Collaboration, Kampala, Uganda.; Department of Obstetrics and Gynaecology, BJ Government Medical College, Pune, India.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.