Journal Article > ResearchFull Text
N Engl J Med. 2011 October 20; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, et al.
N Engl J Med. 2011 October 20; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
Journal Article > LetterFull Text
N Engl J Med. 2015 June 18; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275
Akerlund E, Prescott JB, Tampellini L
N Engl J Med. 2015 June 18; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275
Journal Article > LetterSubscription Only
N Engl J Med. 2016 July 14; Volume 375 (Issue 2); 190-192.; DOI:10.1056/NEJMc1605388
Isanaka S, Adehossi E, Grais RF
N Engl J Med. 2016 July 14; Volume 375 (Issue 2); 190-192.; DOI:10.1056/NEJMc1605388
Journal Article > LetterFull Text
N Engl J Med. 2016 August 18; Volume 375 (Issue 7); e12.; DOI:10.1056/NEJMc1607285
Azman AS, Luquero FJ
N Engl J Med. 2016 August 18; Volume 375 (Issue 7); e12.; DOI:10.1056/NEJMc1607285
Journal Article > LetterSubscription Only
N Engl J Med. 2008 November 27; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Cox HS, Sibilia C, Feuerriegel S, Kalon S, Polonsky JA, et al.
N Engl J Med. 2008 November 27; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Journal Article > ResearchAbstract
N Engl J Med. 2020 June 18; Volume 382; 2397-2410.; DOI:10.1056/NEJMoa1910708
Blanc FX, Badje AD, Bonnet MMB, Gabillard D, Messou E, et al.
N Engl J Med. 2020 June 18; Volume 382; 2397-2410.; DOI:10.1056/NEJMoa1910708
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.
ClinicalTrials.gov number NCT02057796
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.
ClinicalTrials.gov number NCT02057796
Journal Article > ResearchFull Text
N Engl J Med. 2016 June 23; Volume 374 (Issue 25); DOI:10.1056/NEJMoa1513137
Ménard D, Khim N, Beghain J, Adegnika AA, Alam MS, et al.
N Engl J Med. 2016 June 23; Volume 374 (Issue 25); DOI:10.1056/NEJMoa1513137
Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
Journal Article > CommentaryFull Text
N Engl J Med. 2015 January 22; Volume 372 (Issue 4); DOI:10.1056/NEJMp1414730
Ellman T
N Engl J Med. 2015 January 22; Volume 372 (Issue 4); DOI:10.1056/NEJMp1414730
Journal Article > LetterSubscription Only
N Engl J Med. 2008 July 24; Volume 359 (Issue 4); 431-432.; DOI: 10.1056/NEJMc080419
Luquero FJ, Grais RF
N Engl J Med. 2008 July 24; Volume 359 (Issue 4); 431-432.; DOI: 10.1056/NEJMc080419
Journal Article > CommentaryFull Text
N Engl J Med. 2015 October 14 (Issue 15)
Sprecher A
N Engl J Med. 2015 October 14 (Issue 15)