• Something wrong with this record ?

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

J. O'Connor, MJ. Vjecha, AN. Phillips, B. Angus, D. Cooper, B. Grinsztejn, G. Lopardo, S. Das, R. Wood, A. Wilkin, H. Klinker, P. Kantipong, KL. Klingman, D. Jilich, E. Herieka, E. Denning, I. Abubakar, F. Gordin, JD. Lundgren, . ,

. 2017 ; 4 (3) : e105-e112. [pub] 20170105

Language English Country Netherlands

Document type Clinical Trial, Journal Article, Randomized Controlled Trial

Persistent link   https://www.medvik.cz/link/bmc17031152

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial. METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048. FINDINGS: Patients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26-0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71-0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50-1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately. INTERPRETATION: Immediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count. FUNDING: National Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

Chaingrai Prachanukroh Hospital Chaingrai Thailand

Department of Infectious and Tropical Diseases 1st Faculty of Medicine Charles University and Na Bulovce Hospital Prague Czech Republic

Department of Infectious Diseases Rigshospitalet University of Copenhagen Copenhagen Denmark

Desmond Tutu HIV Centre Institute of Infectious Disease and Molecular Medicine University of Cape Town South Africa

Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA

Division of Biostatistics University of Minnesota Minneapolis MN USA

Fundación Centro de Estudios Infectológicos Buenos Aires Argentina

HIV and GU Medicine Coventry and Warwickshire Partnership Trust University of Warwick Coventry UK

Institute for Global Health University College London London UK

Oxford Centre for Clinical Tropical Medicine Nuffield Department of Medicine Oxford University Oxford UK

Research Department of Infection and Population Health University College London London UK

Royal Bournemouth Hospital Bournemouth UK

Section on Infectious Diseases Wake Forest University School of Medicine Winston Salem NC USA

STD and AIDS Clinical Research Laboratory Evandro Chagas Clinical Research Institute Rio de Janeiro Brazil

The George Washington University Washington DC USA

The Kirby Institute University of New South Wales Sydney NSW Australia

University of Würzburg Medical Center Department of Internal Medicine 2 Würzburg Germany

Veterans Affairs Medical Center Washington DC USA

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17031152
003      
CZ-PrNML
005      
20171123142120.0
007      
ta
008      
171025s2017 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S2352-3018(16)30216-8 $2 doi
035    __
$a (PubMed)28063815
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a O'Connor, Jemma $u Research Department of Infection and Population Health, University College London, London, UK.
245    10
$a Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial / $c J. O'Connor, MJ. Vjecha, AN. Phillips, B. Angus, D. Cooper, B. Grinsztejn, G. Lopardo, S. Das, R. Wood, A. Wilkin, H. Klinker, P. Kantipong, KL. Klingman, D. Jilich, E. Herieka, E. Denning, I. Abubakar, F. Gordin, JD. Lundgren, . ,
520    9_
$a BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial. METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048. FINDINGS: Patients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26-0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71-0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50-1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately. INTERPRETATION: Immediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count. FUNDING: National Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.
650    _2
$a oportunní infekce doprovázející AIDS $x epidemiologie $7 D017088
650    _2
$a dospělí $7 D000328
650    _2
$a látky proti HIV $x škodlivé účinky $x terapeutické užití $7 D019380
650    12
$a vysoce aktivní antiretrovirová terapie $x škodlivé účinky $7 D023241
650    _2
$a Austrálie $7 D001315
650    _2
$a bakteriální infekce $x epidemiologie $x imunologie $7 D001424
650    12
$a počet CD4 lymfocytů $7 D018791
650    _2
$a rozvrh dávkování léků $7 D004334
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a HIV infekce $x komplikace $x farmakoterapie $x imunologie $x virologie $7 D015658
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a bakteriální pneumonie $x epidemiologie $7 D018410
650    _2
$a proporcionální rizikové modely $7 D016016
650    _2
$a regresní analýza $7 D012044
650    _2
$a tuberkulóza $x epidemiologie $7 D014376
650    _2
$a virová nálož $7 D019562
655    _2
$a klinické zkoušky $7 D016430
655    _2
$a časopisecké články $7 D016428
655    _2
$a randomizované kontrolované studie $7 D016449
700    1_
$a Vjecha, Michael J $u Veterans Affairs Medical Center, Washington, DC, USA.
700    1_
$a Phillips, Andrew N $u Research Department of Infection and Population Health, University College London, London, UK. Electronic address: andrew.phillips@ucl.ac.uk.
700    1_
$a Angus, Brian $u Oxford Centre for Clinical Tropical Medicine, Nuffield Department of Medicine, Oxford University, Oxford, UK. $7 gn_A_00007014
700    1_
$a Cooper, David $u The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
700    1_
$a Grinsztejn, Beatriz $u STD and AIDS Clinical Research Laboratory, Evandro Chagas Clinical Research Institute (IPEC), Rio de Janeiro, Brazil.
700    1_
$a Lopardo, Gustavo $u Fundación Centro de Estudios Infectológicos, Buenos Aires, Argentina.
700    1_
$a Das, Satyajit $u HIV and GU Medicine, Coventry and Warwickshire Partnership Trust, University of Warwick, Coventry, UK.
700    1_
$a Wood, Robin $u Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
700    1_
$a Wilkin, Aimee $u Section on Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
700    1_
$a Klinker, Hartwig $u University of Würzburg Medical Center, Department of Internal Medicine II, Würzburg, Germany.
700    1_
$a Kantipong, Pacharee $u Chaingrai Prachanukroh Hospital, Chaingrai, Thailand.
700    1_
$a Klingman, Karin L $u Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
700    1_
$a Jilich, David $u Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University and Na Bulovce Hospital, Prague, Czech Republic.
700    1_
$a Herieka, Elbushra $u Royal Bournemouth Hospital, Bournemouth, UK.
700    1_
$a Denning, Eileen $u Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
700    1_
$a Abubakar, Ibrahim $u Institute for Global Health, University College London, London, UK. $7 gn_A_00000889
700    1_
$a Gordin, Fred $u Veterans Affairs Medical Center, Washington, DC, USA; The George Washington University, Washington, DC, USA.
700    1_
$a Lundgren, Jens D $u Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
700    1_
$a ,
773    0_
$w MED00193478 $t The lancet. $x 2405-4704 $g Roč. 4, č. 3 (2017), s. e105-e112
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28063815 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20171025 $b ABA008
991    __
$a 20171123142241 $b ABA008
999    __
$a ok $b bmc $g 1254745 $s 992179
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 4 $c 3 $d e105-e112 $e 20170105 $i 2405-4704 $m The lancet. HIV $n Lancet HIV $x MED00193478
LZP    __
$a Pubmed-20171025

Find record

Citation metrics

Archiving options