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
BMC Health Serv Res. 2017 August 22; Volume 17 (Issue 1); DOI:10.1186/s12913-017-2511-x
Choun K, Achanta S, Naik B, Tripathy JP, Thai S, et al.
BMC Health Serv Res. 2017 August 22; Volume 17 (Issue 1); DOI:10.1186/s12913-017-2511-x
Over the last decade, the availability and use of mobile phones have grown exponentially globally and in Cambodia. In the Sihanouk Hospital Centre of Hope(SHCH) in Cambodia about half of all tuberculosis patients referred out to peripheral health facilities for TB treatment initiation or continuation were lost to contact after referral ranging from 19 to 69% between 2008 and 2013. To address this, we implemented a mobile phone-based patient tracking intervention. Here, we report the number and proportion of referred TB patients who could be contacted through a mobile phone and retained in care after the introduction of mobile phone tracking.
Journal Article > ResearchFull Text
Trop Med Int Health. 2013 February 26; Volume 18 (Issue 4); DOI:10.1111/tmi.12060
Vlieghe E, Reid AJ, Harries AD, Lim K, Thai S, et al.
Trop Med Int Health. 2013 February 26; Volume 18 (Issue 4); DOI:10.1111/tmi.12060
OBJECTIVE: The microbiologic causes of bloodstream infections (BSI) may differ between HIV-positive and HIV-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). We retrospectively assessed community-acquired BSI episodes in adults in Cambodia according to HIV status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics. METHODS: Blood cultures were systematically performed in patients suspected of BSI in a referral hospital in Phnom Penh, Cambodia. Data were collected between 1 January 2009 and 31 December 2011. RESULTS: A total of 452 culture-confirmed episodes of BSI were recorded in 435 patients, of whom 17.9% and 82.1% were HIV-positive and HIV-negative, respectively. Escherichia coli accounted for one-third (n = 155, 32.9%) of 471 organisms, with similar rates in both patient groups. Staphylococcus aureus and Salmonella cholereasuis were more frequent in HIV-positive vs. HIV-negative patients (17/88 vs. 38/383 (P = 0.02) and 10/88 vs. 5/383 (P < 0.001)). Burkholderia pseudomallei was more common in HIV-negative than in HIV-positive patients (39/383 vs. 2/88, P < 0.001). High resistance rates among commonly used antibiotics were observed, including 46.6% ceftriaxone resistance among E. coli isolates. Empiric antibiotic treatments were similarly appropriate in both patient groups but did not cover antibiotic-resistant E. coli (both patient groups), S. aureus (both groups) and B. pseudomallei (HIV-negative patients). CONCLUSION: The present data do not warrant different empiric antibiotic regimens for HIV-positive vs. HIV-negative patients in Cambodia. The overall resistance rates compromise the appropriateness of the current treatment guidelines.