Emergence of Antiretroviral Resistant HIV Variants

The emergence of antiretroviral resistant HIV strains has always been an ongoing concern among the medical communities.  HIV infects and replicates extremely rapidly within the host. The replication process is prone to error and can result in a genetically different viral population in each host. Within such diversity, chances are, there will be strains that are resistant to one or multiple classes of antiretroviral therapy (ART). The drug resistant strains can be transmitted, which raises fear of the possibility of a widespread epidemic and the detrimental implications it has on public health. The main concern is that those infected with the drug resistant strains will not respond optimally when they begin ART. Therefore, this primary drug resistance can lead to treatment failure and eventually mortality.

In a recent mathematical model study from San Francisco, researchers designed a complex ART resistance network model to trace the history of ART resistance in San Francisco and to extrapolate and predict future dynamics. The results show that 60% of the current ART resistant strains can cause self-sustaining epidemics, implying a serious emerging threat to public health. [1]

In addition, an observational study done by Wittkop and colleagues[2] shows that 9.5% of HIV patients with primary resistance to at least one drug are at three times the risk of virological failure compared to resistance-free patients.  However, when the initial ART regimen was determined by genotypic resistance testing, patients had similar clinical outcomes regardless of primary drug resistance. Thus, this study reinforces the current treatment guideline for baseline resistance testing in order to determine optimal ART regimen.

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[1] Smith RJ, Okano JT, Kahn JS, et al. Evolutionary dynamics of complex networks of HIV-resistant strains: the case of San Francisco. Science 2010; 327: 697-701.

[2] Wittkop L,  Gunthard HF, de Wolf F, et al. Effects of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV: a European multicohort study. Lancet Infect Dis 2011; published online Feb 28. DOI:10.1016/S1473-3099(11)70032-9.