Clinical Outcomes in Children With Human Immunodeficiency Virus Treated for Nonsevere Tuberculosis in the SHINE Trial
Author:
Chabala Chishala123ORCID, Wobudeya Eric4ORCID, van der Zalm Marieke M5, Kapasa Monica2, Raichur Priyanka6ORCID, Mboizi Robert4, Palmer Megan5ORCID, Kinikar Aarti6ORCID, Hissar Syed7, Mulenga Veronica12ORCID, Mave Vidya6ORCID, Musoke Philippa4, Hesseling Anneke C5ORCID, McIlleron Helen3ORCID, Gibb Diana8ORCID, Crook Angela8ORCID, Turkova Anna8, , Choo Louise, Wills Genevieve, Thomason Margaret J, Teera Jaqueline, Owen-Powell Ellen, LeBeau Kristen, Baptiste David, McGowan Charlotte, Spyer Moira, Lungu Joyce, Zimba Kevin, Zyambo Khozya, Chungu Chalilwe, Tembo Chimuka, Kunda Sharon, Shingalili Ellen, Zulu Semy, Chipoya Terence, Mwanakalanga Habulembe, Chambela Elias, Hankombo Jessy M, Kalumbi Mox Malama, Chola Daniel, Malama Stephen, Nansamba Winnie, Ssenyonga Mark, Ssengooba Willy, Businge Gerald, Workman Jessica, Demers Anne-Marie, Schaaf Simon, Gie Robert, Walters Elisabetta, Zimri Warren, Hoddinott Graeme, van Deventer Anneen, Goussard Pierre, Morrison Julie, Nijampurkar Aparna, Khan Sameer, Joseph Bency, Bhavani Perumal Kannabiran, Prathiksha G, Baskaran Dhanaraj, Gomathi N S, Mythily V, Kumar Hemanth, Chelvi Silambu, Sekar L, Hanna Luke, Ramesh K, Latha Hema, Bharathi S, Banu Parveen, Xavier Dino, Kumar Manjith, Guru K, Kumar Sasi, Kesavan A, Gunasundari A, Mangalambal G, Nagarajan Valarmathi, Shankar Shakeela, Selvi R, Vaishnavi S, Yadav Krishna, Supriya R, Giranab Hema, Seetha A, Mary Stella, Gopika S, Rohini S, Revathy M, Balaji Sarath, Elilarasi S, Ganesh J, Aravind M A, Mulambo Sylvia, Mwanyungwi Hope, Tapse Dharati, Sane Manasi, Abdullah Amina, Nakalanzi Sarah, Williams Cynthia Mukisa, Aarnoutse Rob, Revill Paul, Love-Koh James, Walker Simon, Mugyenyi Peter, Darbyshire Janet, Clayden Polly, Donald Peter, Singh Varinder, Grzemska Malgosia, Swaminathan Soumya, Peto Tim, Mwinga Alwyn, Fielding Katherine, Graham Stephen M, Welch Steven B, Seddon James A, Whittaker Elizabeth, Anderson Suzanne, Grandjean Louis
Affiliation:
1. Department of Paediatrics, School of Medicine, University of Zambia , Lusaka , Zambia 2. Children's Hospital, University Teaching Hospitals , Lusaka , Zambia 3. Faculty of Health Sciences, Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town , South Africa 4. Mulago Hospital, Makerere University–John Hopkins Hospital Research Collaboration , Kampala , Uganda 5. Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University , Cape Town , South Africa 6. Byramjee Jeejeebhoy Medical College, Johns Hopkins University Clinical Research Site , Pune , India 7. Indian Council of Medical Research, National Institute for Research in Tuberculosis , Chennai , India 8. Institute of Clinical Trials and Methodology, Medical Research Council–Clinical Trials Unit at University College London , London , United Kingdom
Abstract
Abstract
Background
Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial.
Methods
SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH.
Results
Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P = .07) but more underweight (weight-for-age z score, −2.3; (3.3, −0.8 versus −1.0; −1.8, −0.2; P < .01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P < .01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241–1134), and CD4% was 16% (10–26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3–4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42).
Conclusions
We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV.
Clinical Trials Registration. ISRCTN63579542.
Funder
Joint Global Health Trials Scheme Wellcome Trust UK Medical Research Council
Publisher
Oxford University Press (OUP)
Cited by
1 articles.
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