HIV infection may be a risk factor for single-drug resistance in tuberculosis infection, and its evolution into multi-drug resistance, according to a brief report in the July 1st issue of the Journal of Infectious Diseases.
Single-drug-resistant strains of tuberculosis (TB) are less common than multi-drug resistant (MDR) strains resistant to both rifampicin (RIF) and isoniazid (INH) – the two cornerstone agents of first-line TB treatment. However, single-drug resistance is sometimes observed. HIV infection – particularly with advanced immune suppression –has been seen as a risk factor for MDR TB, and (in some small studies) for single-drug resistance as well.
In this retrospective study, investigators analysed genotypic and phenotypic characteristics of M. tuberculosis samples isolated from patients in New York City since 1993, and from New Jersey between 1996 and 2001. The analysis was restricted to samples that were either MDR or solely rifampicin-resistant. Genotypically, samples were grouped according to variations in a key genetic fragment known as IS6110-RFLP; the degree of phenotypic susceptibility to rifampicin, isoniazid, streptomycin, ethambutol, and other anti-TB agents was also determined.
In particular, a cluster of specimens isolated from 29 patients was found to be both genotypically related, and either mono-rifampicin-resistant or MDR. Genotypic analysis showed that these 29 samples shared an unusual mutation (a codon duplication at codon 514). All 29 samples were highly resistant to rifampicin (at drug concentrations > 256 µg/mL). Six of the 29 were mono-resistant to rifampicin alone, 22 had subsequently developed resistance to isoniazid (i.e., were MDR), and five of the samples also showed resistance to other antibiotics.
The majority (79%) of the 29 rifampicin-resistant patients were HIV-positive; all but one of the samples were originally collected pre-HAART, between 1993 and 1996.
The investigators believe that there are a number of implications to these findings: firstly, that highly compromised immune function due to untreated HIV infection may allow less-fit, drug-resistant TB strains to flourish. Secondly, that mono-RIF-resistant TB strains rapidly acquire resistance to other drugs as well, explaining why they are rarely identified in isolation.
The report concludes that, in this retrospective study of mostly pre-HAART-era samples of drug-resistant TB from New York City, most patients with rifampicin-resistant or MDR TB were coinfected with HIV, "suggesting that additional drug resistance may readily develop in HIV-seropositive individuals harboring [rifampicin-resistant] M. tuberculosis bacteria, thus contributing to the global rise of MDR-TB."
Reference:
Bifani P et al. The evolution of drug resistance in Mycobacterium tuberculosis: from a mono–rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population. Journal of Infectious Diseases 2008;198:90–94.