UCSF

As the human immunodeficiency virus (HIV-1) epidemic enters its fourth decade, we continue to advance our understanding of viral transmission, pathogenesis, epidemiology, prevention, and antiretroviral (ARV) treatment. Although this expanding knowledge has helped us manage and decrease morbidity and mortality for persons living with HIV-1 infection, patients on therapy must deal with long-term challenges and complications of therapy. One of these complications is the development of drug resistance. The presence of HIV-1 drug resistance can affect a person's response to treatment and lead to therapy failure. Once resistance-associated mutations are acquired it is permanently integrated into the host's viral genome and its clinical impact will wax and wane depending on selective drug pressure that is present. This is why HIV drug resistance is often considered to be an irreversible complication of ARV therapy.

The first ARV regimen provides the best chance of success in achieving HIV-1 RNA suppression and immune recovery. Historically, each subsequent regimen has had a decreasing chance of success because these regimens possessed challenges with regard to patient tolerability and adherence. The introduction of more potent therapies, improved tolerability profiles, and less toxic regimens have increased the chance of success with second- and third-line regimens. This however does not negate the impact that drug resistance has on a patient's chance for successful therapy. Failing a regimen is not inconsequential and if the underlying reasons for failure are not addressed, subsequent regimen failures may leave patients with limited treatment options. In order to maximize ARV therapy response, treatment guidelines recommend utilization of HIV drug resistance testing prior to initiation for treatment-naïve patients, for patients failing ARV therapy, and for women prior to starting prenatal treatment regimens. Developing expertise in how to interpret resistance test results is crucial in a provider's repertoire of clinical management skills. As resistance testing technologies evolve, it is increasingly critical to stay abreast of advances in the science and translational application of these assays into clinical practice.