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Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

ABSTRACT: Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.

SUBMITTER: Dinic L

PROVIDER: S-EPMC3421781 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

Dinic Lana L Akande Patrick P Idigbe Emmanuel Oni EO Ani Agatha A Onwujekwe Dan D Agbaji Oche O Akanbi Maxwell M Nwosu Rita R Adeniyi Bukola B Wahab Maureen M Lekuk Chindak C Kunle-Ope Chioma C Nwokoye Nkiru N Kanki Phyllis P

Journal of clinical microbiology 20120627 9

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR an ...[more]

PMID: 22740709

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Project description:BackgroundWe aimed to determine the relationship between common pre-existing comorbidities in patients with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with rates of all-cause mortality after TB treatment.MethodsWe conducted a retrospective cohort study among patients treated for rifampicin-resistant and multi/extensively drug resistant (RR and M/XDR) TB in the country of Georgia during 2009-2017. Eligible participants were >15 years of age with newly diagnosed, laboratory-confirmed drug resistant TB who received second-line treatment. Exposures included HIV serologic status, diabetes, and HCV status. The primary outcome was post-TB treatment mortality determined by cross-validating vital status with Georgia's national death registry through November 2019. We estimated hazard rate ratios (HR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without pre-existing comorbidities using cause-specific hazard regressions.ResultsAmong 1032 eligible patients included in our analyses, 34 (3.3%) participants died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (IQR 7-39) after TB treatment ended. After adjusting for potential confounders, the hazard rates of mortality post-TB treatment were higher among participants with HIV co-infection (adjusted hazard ratio [aHR]=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection.ConclusionsIn our cohort, post-TB mortality occurred most commonly in the first three years after TB treatment ended. Additional post-TB care and follow-up, especially among patients with TB and comorbidities (especially HIV co-infection), may reduce rates of mortality post-TB treatment.SummaryOur findings provide evidence that TB patients with comorbidities, especially HIV, may have a significantly increased risk of post-TB mortality compared to those without comorbidities. We also found that most post-TB mortality occurred within three years after TB treatment completion.

Dataset Information

Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

Publications

Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

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