Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial
Summary Background WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis...
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| Veröffentlicht in: | The Lancet infectious diseases 2014-07, Vol.14 (7), p.563-571 |
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| creator | Mfinanga, Sayoki G, PhD Kirenga, Bruce J, MMed Chanda, Duncan M, Dr Mutayoba, Beatrice, MPhil Mthiyane, Thuli, MPH Yimer, Getnet, PhD Ezechi, Oliver, MPH Connolly, Cathy, MPH Kapotwe, Vincent, DipDM Muwonge, Catherine, MSc Massaga, Julius, PhD Sinkala, Edford, MMed Kohi, Wanze, MPH Lyantumba, Lucinda, BA Nyakoojo, Grace, BA Luwaga, Henry, MA Doulla, Basra, BSc Mzyece, Judith, BSc Kapata, Nathan, MBChB Vahedi, Mahnaz, MBBS Mwaba, Peter, FRCP Egwaga, Saidi, MMed Adatu, Francis, MSc Pym, Alex, PhD Joloba, Moses, Prof Rustomjee, Roxana, MD Zumla, Alimuddin, Prof Onyebujoh, Philip, FRCP |
| description | Summary Background WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more. Methods We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220–349 cells per μL vs ≥350 cells per μL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). Findings We screened 13 588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64–1·30; p=0·9). Of patients with a CD4 cell count of 220–349 cells per μL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46–1·39; p=0·6). For those with 350 cells per μL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63–1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8–2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). Interpretation ART can be delayed until af |
| doi_str_mv | 10.1016/S1473-3099(14)70733-9 |
| format | Article |
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We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more. Methods We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220–349 cells per μL vs ≥350 cells per μL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). Findings We screened 13 588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64–1·30; p=0·9). Of patients with a CD4 cell count of 220–349 cells per μL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46–1·39; p=0·6). For those with 350 cells per μL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63–1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8–2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). Interpretation ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly. Funding USAID, Zambia Ministry of Health, Tanzania Commission for Science and Technology, WHO-TDR.</description><identifier>ISSN: 1473-3099</identifier><identifier>EISSN: 1474-4457</identifier><identifier>DOI: 10.1016/S1473-3099(14)70733-9</identifier><identifier>PMID: 24810491</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Acquired immune deficiency syndrome ; Adult ; AIDS ; Anti-HIV Agents - administration & dosage ; Antiretroviral agents ; Antiretroviral Therapy, Highly Active - methods ; Bacterial diseases ; Bacterial diseases of the respiratory system ; Biological and medical sciences ; CD4 Lymphocyte Count - methods ; Drug Administration Schedule ; Drug therapy ; Female ; HIV ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - microbiology ; HIV Seropositivity - drug therapy ; HIV Seropositivity - microbiology ; Human bacterial diseases ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious Disease ; Infectious diseases ; Male ; Medical sciences ; Mortality ; Mycobacterium ; Prospective Studies ; Tuberculosis ; Tuberculosis and atypical mycobacterial infections ; Tuberculosis, Pulmonary - drug therapy ; Tuberculosis, Pulmonary - immunology ; Tuberculosis, Pulmonary - virology ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. 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All rights reserved.</rights><rights>Copyright Elsevier Limited Jul 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-ce2e46d360a27da46b909b5d6c732afd50901a7596c01922e0ea132a48b2a6653</citedby><cites>FETCH-LOGICAL-c581t-ce2e46d360a27da46b909b5d6c732afd50901a7596c01922e0ea132a48b2a6653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1473309914707339$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28595401$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24810491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mfinanga, Sayoki G, PhD</creatorcontrib><creatorcontrib>Kirenga, Bruce J, MMed</creatorcontrib><creatorcontrib>Chanda, Duncan M, Dr</creatorcontrib><creatorcontrib>Mutayoba, Beatrice, MPhil</creatorcontrib><creatorcontrib>Mthiyane, Thuli, MPH</creatorcontrib><creatorcontrib>Yimer, Getnet, PhD</creatorcontrib><creatorcontrib>Ezechi, Oliver, MPH</creatorcontrib><creatorcontrib>Connolly, Cathy, MPH</creatorcontrib><creatorcontrib>Kapotwe, Vincent, DipDM</creatorcontrib><creatorcontrib>Muwonge, Catherine, MSc</creatorcontrib><creatorcontrib>Massaga, Julius, PhD</creatorcontrib><creatorcontrib>Sinkala, Edford, MMed</creatorcontrib><creatorcontrib>Kohi, Wanze, MPH</creatorcontrib><creatorcontrib>Lyantumba, Lucinda, BA</creatorcontrib><creatorcontrib>Nyakoojo, Grace, BA</creatorcontrib><creatorcontrib>Luwaga, Henry, MA</creatorcontrib><creatorcontrib>Doulla, Basra, BSc</creatorcontrib><creatorcontrib>Mzyece, Judith, BSc</creatorcontrib><creatorcontrib>Kapata, Nathan, MBChB</creatorcontrib><creatorcontrib>Vahedi, Mahnaz, MBBS</creatorcontrib><creatorcontrib>Mwaba, Peter, FRCP</creatorcontrib><creatorcontrib>Egwaga, Saidi, MMed</creatorcontrib><creatorcontrib>Adatu, Francis, MSc</creatorcontrib><creatorcontrib>Pym, Alex, PhD</creatorcontrib><creatorcontrib>Joloba, Moses, Prof</creatorcontrib><creatorcontrib>Rustomjee, Roxana, MD</creatorcontrib><creatorcontrib>Zumla, Alimuddin, Prof</creatorcontrib><creatorcontrib>Onyebujoh, Philip, FRCP</creatorcontrib><title>Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial</title><title>The Lancet infectious diseases</title><addtitle>Lancet Infect Dis</addtitle><description>Summary Background WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more. Methods We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220–349 cells per μL vs ≥350 cells per μL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). Findings We screened 13 588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64–1·30; p=0·9). Of patients with a CD4 cell count of 220–349 cells per μL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46–1·39; p=0·6). For those with 350 cells per μL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63–1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8–2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). Interpretation ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly. Funding USAID, Zambia Ministry of Health, Tanzania Commission for Science and Technology, WHO-TDR.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>AIDS</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral Therapy, Highly Active - methods</subject><subject>Bacterial diseases</subject><subject>Bacterial diseases of the respiratory system</subject><subject>Biological and medical sciences</subject><subject>CD4 Lymphocyte Count - methods</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - microbiology</subject><subject>HIV Seropositivity - drug therapy</subject><subject>HIV Seropositivity - microbiology</subject><subject>Human bacterial diseases</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mortality</subject><subject>Mycobacterium</subject><subject>Prospective Studies</subject><subject>Tuberculosis</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Tuberculosis, Pulmonary - drug therapy</subject><subject>Tuberculosis, Pulmonary - immunology</subject><subject>Tuberculosis, Pulmonary - virology</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>1473-3099</issn><issn>1474-4457</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNktFqFDEUhgdRbK0-ghIQYQsdTSbJzMYLpZbqFgqCVm9DNnO2m5qdjElmy76qT-OZ3dVCb_QqYfLlyz-HvyieM_qaUVa_-cpEw0tOlZowcdzQhvNSPSgO8bMohZDNw-1-hxwUT1K6oZQ1jIrHxUElprhR7LD4dW6i35A1xDQk0oI3G2iJ61x2JrvQkbAgS3e9RMbY7NZATJddhBzD2kXjSV5CNP2GLEIks4vvZR-S23Ht4HMity4vSQe3KGidue5CQn8_-FXoTNyQPMwh2sHjrUQmVx_K2enpl6vjt8SQPobUw_bRE0yUIXbbSMafkGi6Nqwcuk5I742FeSht6DCV9-jP0Rn_tHi0MD7Bs_16VHz7eH51NisvP3-6ODu9LK2cslxaqEDULa-pqZrWiHquqJrLtrYNr8yilVRRZhqpakuZqiqgYBieiOm8MnUt-VEx2Xkx8M8BUtYYzIL3poMwJM2kZLWQkv8PKhifVhWvEX15D70JA07AjxRX1ZRTOgrljrI4rBRhofvoVjhYzagee6K3PdFjCTQTetsTrfDei719mK-g_XvrTzEQeLUHTLLGL3Dg1qU7biqVFHTk3u84wAmvHUSdrIPOQoslsVm3wf0zyrt7Buuxf_joD9hAuvtrnSpNd5LRgetoUPw3cAXyeQ</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Mfinanga, Sayoki G, PhD</creator><creator>Kirenga, Bruce J, MMed</creator><creator>Chanda, Duncan M, Dr</creator><creator>Mutayoba, Beatrice, MPhil</creator><creator>Mthiyane, Thuli, MPH</creator><creator>Yimer, Getnet, PhD</creator><creator>Ezechi, Oliver, MPH</creator><creator>Connolly, Cathy, MPH</creator><creator>Kapotwe, Vincent, DipDM</creator><creator>Muwonge, Catherine, MSc</creator><creator>Massaga, Julius, PhD</creator><creator>Sinkala, Edford, MMed</creator><creator>Kohi, Wanze, MPH</creator><creator>Lyantumba, Lucinda, BA</creator><creator>Nyakoojo, Grace, BA</creator><creator>Luwaga, Henry, MA</creator><creator>Doulla, Basra, BSc</creator><creator>Mzyece, Judith, BSc</creator><creator>Kapata, Nathan, MBChB</creator><creator>Vahedi, Mahnaz, MBBS</creator><creator>Mwaba, Peter, FRCP</creator><creator>Egwaga, Saidi, MMed</creator><creator>Adatu, Francis, MSc</creator><creator>Pym, Alex, PhD</creator><creator>Joloba, Moses, Prof</creator><creator>Rustomjee, Roxana, MD</creator><creator>Zumla, Alimuddin, Prof</creator><creator>Onyebujoh, Philip, FRCP</creator><general>Elsevier Ltd</general><general>Lancet Publishing Group</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20140701</creationdate><title>Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial</title><author>Mfinanga, Sayoki G, PhD ; Kirenga, Bruce J, MMed ; Chanda, Duncan M, Dr ; Mutayoba, Beatrice, MPhil ; Mthiyane, Thuli, MPH ; Yimer, Getnet, PhD ; Ezechi, Oliver, MPH ; Connolly, Cathy, MPH ; Kapotwe, Vincent, DipDM ; Muwonge, Catherine, MSc ; Massaga, Julius, PhD ; Sinkala, Edford, MMed ; Kohi, Wanze, MPH ; Lyantumba, Lucinda, BA ; Nyakoojo, Grace, BA ; Luwaga, Henry, MA ; Doulla, Basra, BSc ; Mzyece, Judith, BSc ; Kapata, Nathan, MBChB ; Vahedi, Mahnaz, MBBS ; Mwaba, Peter, FRCP ; Egwaga, Saidi, MMed ; Adatu, Francis, MSc ; Pym, Alex, PhD ; Joloba, Moses, Prof ; Rustomjee, Roxana, MD ; Zumla, Alimuddin, Prof ; Onyebujoh, Philip, FRCP</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c581t-ce2e46d360a27da46b909b5d6c732afd50901a7596c01922e0ea132a48b2a6653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adult</topic><topic>AIDS</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral Therapy, Highly Active - methods</topic><topic>Bacterial diseases</topic><topic>Bacterial diseases of the respiratory system</topic><topic>Biological and medical sciences</topic><topic>CD4 Lymphocyte Count - methods</topic><topic>Drug Administration Schedule</topic><topic>Drug therapy</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - microbiology</topic><topic>HIV Seropositivity - drug therapy</topic><topic>HIV Seropositivity - microbiology</topic><topic>Human bacterial diseases</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious Disease</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mortality</topic><topic>Mycobacterium</topic><topic>Prospective Studies</topic><topic>Tuberculosis</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Tuberculosis, Pulmonary - drug therapy</topic><topic>Tuberculosis, Pulmonary - immunology</topic><topic>Tuberculosis, Pulmonary - virology</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mfinanga, Sayoki G, PhD</creatorcontrib><creatorcontrib>Kirenga, Bruce J, MMed</creatorcontrib><creatorcontrib>Chanda, Duncan M, Dr</creatorcontrib><creatorcontrib>Mutayoba, Beatrice, MPhil</creatorcontrib><creatorcontrib>Mthiyane, Thuli, MPH</creatorcontrib><creatorcontrib>Yimer, Getnet, PhD</creatorcontrib><creatorcontrib>Ezechi, Oliver, MPH</creatorcontrib><creatorcontrib>Connolly, Cathy, MPH</creatorcontrib><creatorcontrib>Kapotwe, Vincent, DipDM</creatorcontrib><creatorcontrib>Muwonge, Catherine, MSc</creatorcontrib><creatorcontrib>Massaga, Julius, PhD</creatorcontrib><creatorcontrib>Sinkala, Edford, MMed</creatorcontrib><creatorcontrib>Kohi, Wanze, MPH</creatorcontrib><creatorcontrib>Lyantumba, Lucinda, BA</creatorcontrib><creatorcontrib>Nyakoojo, Grace, BA</creatorcontrib><creatorcontrib>Luwaga, Henry, MA</creatorcontrib><creatorcontrib>Doulla, Basra, BSc</creatorcontrib><creatorcontrib>Mzyece, Judith, BSc</creatorcontrib><creatorcontrib>Kapata, Nathan, MBChB</creatorcontrib><creatorcontrib>Vahedi, Mahnaz, MBBS</creatorcontrib><creatorcontrib>Mwaba, Peter, FRCP</creatorcontrib><creatorcontrib>Egwaga, Saidi, MMed</creatorcontrib><creatorcontrib>Adatu, Francis, MSc</creatorcontrib><creatorcontrib>Pym, Alex, PhD</creatorcontrib><creatorcontrib>Joloba, Moses, Prof</creatorcontrib><creatorcontrib>Rustomjee, Roxana, MD</creatorcontrib><creatorcontrib>Zumla, Alimuddin, Prof</creatorcontrib><creatorcontrib>Onyebujoh, Philip, FRCP</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mfinanga, Sayoki G, PhD</au><au>Kirenga, Bruce J, MMed</au><au>Chanda, Duncan M, Dr</au><au>Mutayoba, Beatrice, MPhil</au><au>Mthiyane, Thuli, MPH</au><au>Yimer, Getnet, PhD</au><au>Ezechi, Oliver, MPH</au><au>Connolly, Cathy, MPH</au><au>Kapotwe, Vincent, DipDM</au><au>Muwonge, Catherine, MSc</au><au>Massaga, Julius, PhD</au><au>Sinkala, Edford, MMed</au><au>Kohi, Wanze, MPH</au><au>Lyantumba, Lucinda, BA</au><au>Nyakoojo, Grace, BA</au><au>Luwaga, Henry, MA</au><au>Doulla, Basra, BSc</au><au>Mzyece, Judith, BSc</au><au>Kapata, Nathan, MBChB</au><au>Vahedi, Mahnaz, MBBS</au><au>Mwaba, Peter, FRCP</au><au>Egwaga, Saidi, MMed</au><au>Adatu, Francis, MSc</au><au>Pym, Alex, PhD</au><au>Joloba, Moses, Prof</au><au>Rustomjee, Roxana, MD</au><au>Zumla, Alimuddin, Prof</au><au>Onyebujoh, Philip, FRCP</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial</atitle><jtitle>The Lancet infectious diseases</jtitle><addtitle>Lancet Infect Dis</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>14</volume><issue>7</issue><spage>563</spage><epage>571</epage><pages>563-571</pages><issn>1473-3099</issn><eissn>1474-4457</eissn><coden>LANCAO</coden><abstract>Summary Background WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more. Methods We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220–349 cells per μL vs ≥350 cells per μL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). Findings We screened 13 588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64–1·30; p=0·9). Of patients with a CD4 cell count of 220–349 cells per μL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46–1·39; p=0·6). For those with 350 cells per μL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63–1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8–2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). Interpretation ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly. Funding USAID, Zambia Ministry of Health, Tanzania Commission for Science and Technology, WHO-TDR.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>24810491</pmid><doi>10.1016/S1473-3099(14)70733-9</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1473-3099 |
| ispartof | The Lancet infectious diseases, 2014-07, Vol.14 (7), p.563-571 |
| issn | 1473-3099 1474-4457 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - administration & dosage Antiretroviral agents Antiretroviral Therapy, Highly Active - methods Bacterial diseases Bacterial diseases of the respiratory system Biological and medical sciences CD4 Lymphocyte Count - methods Drug Administration Schedule Drug therapy Female HIV HIV Infections - drug therapy HIV Infections - immunology HIV Infections - microbiology HIV Seropositivity - drug therapy HIV Seropositivity - microbiology Human bacterial diseases Human immunodeficiency virus Human viral diseases Humans Infectious Disease Infectious diseases Male Medical sciences Mortality Mycobacterium Prospective Studies Tuberculosis Tuberculosis and atypical mycobacterial infections Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - virology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial |
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