Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults.
AIDS-Related Opportunistic Infections
/ diagnosis
Adult
Anti-Retroviral Agents
/ therapeutic use
Antitubercular Agents
/ therapeutic use
Bacterial Infections
/ epidemiology
CD4 Lymphocyte Count
Female
HIV
HIV Infections
/ complications
Humans
Immunocompromised Host
Male
Tuberculosis
/ complications
Viral Load
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
18 06 2020
18 06 2020
Historique:
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
14
7
2020
Statut:
ppublish
Résumé
In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).
Sections du résumé
BACKGROUND
In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death.
METHODS
We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization.
RESULTS
A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment.
CONCLUSIONS
Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).
Identifiants
pubmed: 32558469
doi: 10.1056/NEJMoa1910708
doi:
Substances chimiques
Anti-Retroviral Agents
0
Antitubercular Agents
0
Banques de données
ClinicalTrials.gov
['NCT02057796']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2397-2410Subventions
Organisme : Agence Nationale de Recherches sur le Sida et les Hépatites Virales
ID : ANRS 12290
Pays : International
Investigateurs
Kakou Aka
(K)
Eba Aoussi
(E)
Emmanuel Bissagnene
(E)
Serge Eholié
(S)
Frédéric Ello
(F)
Gustave Nzunetu
(G)
Cyprien Rabe
(C)
Baba Sidibé
(B)
Florence Adjé
(F)
Boris Ahonou
(B)
Jacqueline Amani
(J)
Amani Anzian
(A)
Anicet Assoua
(A)
Lucien Ayemou
(L)
Glao Diomandé
(G)
Patrice Gouesse
(P)
Loukou Kati-Coulibaly
(L)
Lambert Konan
(L)
Edwige Konan
(E)
Francis Kouadio
(F)
Eugène Messou
(E)
Lucie N'Dry
(L)
Ida Zadi
(I)
Rinah Arinaitwe
(R)
Maryline Bonnet
(M)
Claire Kesande
(C)
Isaac Ampaire
(I)
Rodgers Kajabwangu
(R)
Stella Kyasiimire
(S)
Rose Kyarimpa
(R)
Conrad Muzoora
(C)
Doreen Mpeirwe
(D)
Gaudioza Mugabirwe
(G)
Eva Natukunda
(E)
Naome Natukunda
(N)
Masturah Nakanwagi
(M)
Junenal Nkeramahame
(J)
Miria Nyangoma
(M)
Colman Tayebwa
(C)
Penh Sun Ly
(PS)
Kuong Chan
(K)
Virin Chhneang
(V)
Samnang Khiev
(S)
Setha Lim Sreng
(SL)
Nary Long
(N)
Makara Ly
(M)
Suon Sopheak Ma
(SS)
Kimcolin Mao
(K)
Panharoat Men
(P)
Sovannary Mol
(S)
Vandoeun Nhem
(V)
Navy Nin
(N)
Moeung Roeun
(M)
Manith So
(M)
Mary Sos
(M)
Thim Sotheara
(T)
Narith Uk
(N)
Sokha Um
(S)
Tan Eang Mao
(TE)
Che Yanith
(C)
Socheat Chim
(S)
Bun Than Chum
(BT)
Doung Dara
(D)
Chanthy Din
(C)
Panha Eng
(P)
Putheary Hang
(P)
Savorn Im
(S)
Karona Keo
(K)
Sok Lida Khem
(SL)
Phirum Lay
(P)
Phalla Leng
(P)
Kalyan Ouk
(K)
Reaksmey Pe
(R)
Thong Phe
(T)
Bunthy Phoung
(B)
Mono Rouen
(M)
Sok Leang San
(SL)
Teav Sina
(T)
Pichsovannary Srey
(P)
Seakly Sun
(S)
Sopheak Thai
(S)
Chhun Heng Veng
(CH)
Young Suntouch
(Y)
Le Minh Tri Dang
(LMT)
Quoc Dung Lam
(QD)
Dr Hong Ngoc Le
(DHN)
Duc Bang Nguyen
(DB)
Thi Hieu Nguyen
(TH)
Thi Hong Nguyen
(TH)
Huu Minh Nguyen
(HM)
Van Song Nguyen
(VS)
Ha Uyen Nguyen
(HU)
Nhu Viet Nguyen
(NV)
Thi Bich Yen Nguyen
(TBY)
Thi Tuong Vy Pham
(TTV)
Ngoc Thach Tran
(NT)
Pham Phuong Thao Tran
(PPT)
My Huong To
(MH)
Huu Lân Nguyen
(HL)
Thi Quynh Anh Nguyen
(TQA)
Hung Cuong Pham
(HC)
Thi Thuy Nga Nguyen
(TTN)
Kim Ung Quach
(KU)
Thi Thu Van Tieu
(TTV)
Hugues Ahiboh
(H)
Arlette Emieme
(A)
André Inwoley
(A)
Mathieu Kabran
(M)
Hervé Menan
(H)
Timothée Ouassa
(T)
Thomas-d'Aquin Toni
(TD)
Arnold Ayabare
(A)
Kennedy Kassaza
(K)
Ronald Kabanda
(R)
Sulaiman Muwanga
(S)
Aisha Nalusaji
(A)
Deborah Nanjebe
(D)
Patrick Orikiriza
(P)
Ivan Taremwa Mugisha
(IT)
Esther Turyashemererwa
(E)
Thadeous Turuho
(T)
Sokleaph Cheng
(S)
Seiha Heng
(S)
Alexandra Kerléguer
(A)
Daly Chea
(D)
Chandara Mom
(C)
Sophana Pich
(S)
Sandap Sar
(S)
Ngoc Lan Nguyen
(NL)
Thi Cao Van Nguyen
(TCV)
Huu Loc Tran
(HL)
Xuan Thinh Vu
(XT)
Khanh Thu Huynh
(KT)
Que Anh Luong
(QA)
Thi Xuan Lien Truong
(TXL)
Adrienne Aboua
(A)
Irmine Ahyi
(I)
Anani Badjé
(A)
Adoulaye Cissé
(A)
Christine Danel
(C)
Allé Baba Dieng
(AB)
Serge K Domoua
(SK)
Sylvain Juchet
(S)
Romuald Konan
(R)
Célestin N'Chot
(C)
Larissa N'guessan Koffi
(LN)
Sylvie Konan
(S)
Suzanne Kouadio
(S)
Gérard Menan
(G)
Raoul Moh
(R)
Bertine Siloué
(B)
Cyril Yao-Yapi
(C)
Xavier Anglaret
(X)
Delphine Gabillard
(D)
Jérôme Le Carrou
(J)
Sophie Karcher
(S)
Gwenaëlle Clouet
(G)
François-Xavier Blanc
(FX)
Didier Laureillard
(D)
Stephen D Lawn
(SD)
Laurence Borand
(L)
Bunnet Dim
(B)
Morina Hek
(M)
Brembrey Him
(B)
Monorea Keo
(M)
Boraneath Nang
(B)
Sophea Suom
(S)
Sreymom Thaan
(S)
Thi Thanh Dinh
(TT)
Anaïs Domergue
(A)
Frédérique Guiroy
(F)
Quoc Khanh Le
(QK)
Delphine Rapoud
(D)
Thi Hong Tran
(TH)
Thi Hai Ly Tran
(THL)
Commentaires et corrections
Type : CommentIn
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