Navigating resistance pathways

One of the most daunting challenges facing HIV-treating clinicians is the persistent spectre of treatment failure in their patients.

There are several factors involved in the development of treatment failure in HIV-infected patients including preexisting resistant viral variants; the potency of the drugs used (and thus the barrier to resistance of each drug and the regimen as a whole); patient-specific factors, such as adherence; and pharmacologic factors. Host immunologic status is also important because the more advanced the disease is, the less likely it is that a complete response to antiretroviral therapy will occur.

These factors, when combined, can result in incomplete suppression of viral replication and, in the setting of persistent viral replication, a greater opportunity for drug resistance mutations to emerge. The emergence of these mutations initiates a cycle of less treatment efficacy, less viral suppression, more viral replication, and broader cross-resistance, which cycles back to less treatment efficacy and ultimately leads to failure of the regimen.