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Opportunistic Infections: TB, HIV, and XDR TB

Data presented at the 15th Retrovirus Conference highlighted the importance of strengthening airborne infection-control practice and relying less on hospital TB care, particularly in resource-limited settings.

Drug-resistant tuberculosis (TB) has emerged as a major clinical and public health challenge, particularly in areas of sub-Saharan Africa that have a high prevalence of HIV infection. At the 15th Retrovirus Conference, new information was presented about the burgeoning epidemic of drug-resistant TB worldwide and about the development of several promising new TB drugs.

In November 2006, we reported a highly fatal outbreak of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB in a rural subdistrict of KwaZulu-Natal, South Africa; all of the cases occurred among HIV-infected persons, and there was strong evidence of nosocomial transmission existed (ACC Nov 13 2006). Since then, the number of new cases in this subdistrict has continued to grow, the mortality rate has remained extremely high, and almost all known affected individuals have been coinfected with HIV [Abstract 112]. Furthermore, the geographic extent of the epidemic has widened considerably; XDR TB has now been diagnosed in nearly 60 healthcare facilities in KwaZulu-Natal, in all nine provinces in South Africa, and in bordering countries. Preliminary information from the Ukraine illustrates that the convergence of HIV and drug-resistant TB is not confined solely to sub-Saharan Africa and also is occurring in Eastern Europe [Abstract 144].

Most cases of drug-resistant TB worldwide are believed to result from failure of TB therapy, because of either patient nonadherence or programmatic inadequacy. However, a recent study from South Africa underscores the importance of primary or transmitted drug resistance, particularly in congregate healthcare settings in areas with high rates of TB/HIV coinfection [Abstract 143]. Using drug-susceptibility testing and molecular fingerprinting of TB isolates, investigators confirmed that recent nosocomial transmission was of great importance in driving the devastating epidemic of XDR TB in South Africa. Isolates were analyzed from 17 patients who initially had drug-susceptible TB and developed MDR or XDR TB. All had been hospitalized for TB treatment and were coinfected with HIV. In all cases, the genotype of the follow-up isolate differed from that of the initial isolate, indicating exogenous reinfection. Two genotypes (ST 34 and ST 60, associated with MDR and XDR TB, respectively) were responsible for 85% of reinfections.

No truly novel compounds for the treatment of TB have been available during the past 40 years. However, research and development of new TB drugs is extremely encouraging [Abstract 110]. In addition to fluoroquinolones, five new TB drugs are in the pipeline. Two — TMC-207 (a diarylquinoline) and OPC-67683 (a nitroimidazole) — are currently being evaluated in phase II trials, and three others — PA-824, LL-3858, and SQ-109 — are in phase I trials. These agents, in combination with existing or new drugs, hold promise for reducing the duration of TB therapy to less than 4 months and, eventually, for providing effective treatment of XDR TB.

Given that effective treatment is currently unavailable for XDR TB, the importance of preventing transmission cannot be overstated. Two of our best strategies are to strengthen airborne infection-control practice and to rely less on hospital TB care, particularly in resource-limited settings.

— Gerald H. Friedland, MD

Dr. Friedland presented this information at the 15th Retrovirus Conference (Abstract 112) and is an investigator on the study described in Abstract 143.

Published in AIDS Clinical Care March 10, 2008