HIV treatment adherence, drug resistance, virologic failure: evolving concepts

Abstract

Poor adherence to combined antiretroviral therapy (cART) has been shown to be a major determinant of virologic failure, emergence of drug resistant virus, disease progression, hospitalizations, mortality, and health care costs. While high adherence levels can be achieved in both resource-rich and resource-limited settings following initiation of cART, long-term adherence remains a challenge regardless of available resources. Barriers to optimal adherence may originate from individual (biological, socio-cultural, behavioral), pharmacological, and societal factors. Although patients and providers should continuously strive for maximum adherence to cART, there is accumulating evidence that each class of antiretroviral therapy has specific adherence-drug resistance relationship characteristics allowing certain regimens more flexibility than others. There is not a universally accepted measure for cART adherence, since each method has distinct advantages and disadvantages including cost, complexity, accuracy, precision, intrusiveness and bias. Development of a real-time cART adherence monitoring tool will enable the development of novel, pre-emptive adherence-improving strategies. The application of these strategies may ultimately prove to be the most cost-effective method to reduce morbidity and mortality for the individual and decrease the likelihood of HIV transmission and emergence of resistance in the community.

Fig. (1)

Determinants of HIV Treatment Success and Outcomes.

Fig. (2)

Emergence of Resistant Viral Population due To Selective Drug Pressure.

Fig. (3)

Inverted “U-Shaped” Hypothetical Curve of the Relationship Between Probability of Drug Resistance and HIV Treatment Adherence Levels.

Fig. (4)

Probability of Resistance by Adherence Level and Class of Antiretroviral Therapy Regimen (adapted from reference 60, with permission from Oxford University Press, June 30, 2010).