title: 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.
authors: Harvard School of Public Health, Immunology and Infectious Diseases, Boston, Massachusetts, USA.
authors: Lana
authors: L
authors: Dinic
authors: Patrick
authors: P
authors: Akande
authors: Emmanuel Oni
authors: EO
authors: Idigbe
authors: Agatha
authors: A
authors: Ani
authors: Dan
authors: D
authors: Onwujekwe
authors: Oche
authors: O
authors: Agbaji
authors: Maxwell
authors: M
authors: Akanbi
authors: Rita
authors: R
authors: Nwosu
authors: Bukola
authors: B
authors: Adeniyi
authors: Maureen
authors: M
authors: Wahab
authors: Chindak
authors: C
authors: Lekuk
authors: Chioma
authors: C
authors: Kunle-Ope
authors: Nkiru
authors: N
authors: Nwokoye
authors: Phyllis
authors: P
authors: Kanki
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D005798:Genes, Bacterial; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D009549:Nigeria; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial