Mycobacterium tuberculosis Drug Resistance and Transmission among Human Immunodeficiency Virus-Infected Patients in Ho Chi Minh City, Vietnam

Abstract

Vietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 Mycobacterium tuberculosis isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing M. tuberculosis transmission among HIV-infected patients.

Figure 1.

Drug resistance mutations identified in different Mycobacterium tuberculosis strain lineages.

Figure 2.

Phylogenetic tree of sequenced* Mycobacterium tuberculosis strains from patients with tuberculosis/human immunodeficiency virus coinfection in Ho Chi Minh City, Vietnam. Multidrug resistant (MDR): resistant to at least isoniazid and rifampicin; *All strains that were drug resistant (84) or clustered by 24-locus mycobacterial interspersed repetitive unit (40) were sequenced; Red circles indicate identified clusters; Black circles indicate possible cluster.

Figure 3.

Mycobacterium tuberculosis strains identified in tuberculosis/HIV coinfected patients in Ho Chi Minh City, Vietnam, compared with community strains identified among non-HIV–infected patients.* DR = drug resistant; DS = drug susceptible; HIV = human immunodeficiency virus; MDR = multidrug resistant. *Sequence data for community M. tuberculosis strains were derived from Holt et al.

Figure 4.

Comparison of branch length by Mycobacterium tuberculosis strain lineage in HIV-infected and uninfected patients. HIV = human immunodeficiency virus. This figure appears in color at www.ajtmh.org.