Publications

BACKGROUND

Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure.

METHODS

We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes.

RESULTS

Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p=0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27-5.93; HR 5.50, 95% CI 2.38-12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24-4.52).

CONCLUSIONS

Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.

Cells infected with hepatitis C virus (HCV) become refractory to further infection by HCV (T. Schaller et al., J. Virol. 81:4591-4603, 2007; D. M. Tscherne et al., J. Virol. 81:3693-3703, 2007). This process, termed superinfection exclusion, does not involve downregulation of surface viral receptors but instead occurs inside the cell at the level of RNA replication. The originally infecting virus may occupy replication niches or sequester host factors necessary for viral growth, preventing effective growth of viruses that enter the cell later. However, there appears to be an additional level of intracellular competition between viral genomes that occurs at or shortly following mitosis. In the setting of cellular division, when two viral replicons of equivalent fitness are present within a cell, each has an equal opportunity to exclude the other. In a population of dividing cells, the competition between viral genomes proceeds apace, randomly clearing one or the other genome from cells in the span of 9 to 12 days. These findings demonstrate a new mechanism of intracellular competition between HCV strains, which may act to further limit HCV's genetic diversity and ability to recombine in vivo.