Antiretroviral adherence, drug resistance, viral fitness and HIV disease progression: a tangled web is woven

The clinical goals of HIV treatment are optimally accomplished through consistent high-level adherence to highly active antiretroviral therapy (HAART) and durable suppression of the viral load. However, as a result of the need for lifelong therapy and HIV's prodigious replication rate and error-prone reverse transcriptase, varying amounts of antiretroviral drug resistance are common in treated individuals. Medication adherence is linked to the development of drug resistance, although not by a simple linear relationship. Recent studies have suggested that extensive drug resistance is not a major determinant of HIV disease progression and death. Rather, failure to access care and discontinuation of or non-adherence with therapy are arguably the most important factors associated with HIV disease progression in the HAART era. Other data indicate that continued therapy in the setting of extensive drug resistance and the inability to achieve viral suppression can provide continued clinical benefit. Such benefit may be mediated, at least partially, by reductions in viral fitness associated with drug resistance mutations.