HIV Infection and AIDS: Drug Resistance

Drug Resistance

Drug resistance can be broadly defined as the ability of pathogens to withstand the effects of medications intended to be toxic to them. Resistance develops as a result of spontaneous genetic mutation of the pathogens or in response to exposure to the medication (Esch & Frank, 2001). 

Factors associated with the development of drug resistance include serial monotherapy (tak-ing one medication at a time), inadequate suppression of virus replication with suboptimal treatment regimens, difficulty with adherence to complex and toxic regimens, and initiation of ther-apy late in the course of HIV infection (Boden et al., 1999). HIV-1 may find refuge in organ sanctuaries such as behind the blood–brain barrier, where diminished drug concentrations in the central nervous system (CNS) might induce the development of drug-resistant mutants (Cavert & Haase, 1998). HIV-1 per-sists in lymphoid tissue even in individuals who appear to have responded well to antiviral therapy (Letvin, 1998). Deciding whether the medication regimen is effective or ineffective is a com-plex phenomenon. Some individuals experience an optimal re-sponse to treatment, as shown by effective viral suppression and ensuing immune recovery; others experience increasing CD4+ cell counts in the presence of ongoing viral replication or blunted immune recovery despite viral control, and finally complete treat-ment failure (Perrin & Telenti, 1998).

Central to the complexity of HIV drug resistance are the phe-nomenon of HIV quasi-species (the simultaneous presence in a patient of multiple viral variants), the extent of cross-resistance among antiviral agents, the existence in each individual of archival HIV DNA copies representing all viruses that emerged under the patient’s previous treatment, and the preexistence of resistant variants even without prior exposure to the medication (Perrin

Telenti, 1998). Measurement of HIV drug susceptibility for management of HIV infection is now practical using recombi-nant DNA technology (Hirsch et al., 2000). Although available data support a role for HIV drug resistance testing in selecting medications in many clinical situations, these test results should not be used as the principal criterion for decisions on initiating or changing antiretroviral therapy. Such decisions should be based primarily on the patient’s plasma HIV viral load. Several factors in addition to resistance testing must be considered in choosing medications for a new regimen once the prior regimen has failed. These factors include the patient’s past treatment history, viral load, medication tolerance, the likelihood of the patient adhering to the medication regimen, and concomitant medical conditions or medications (Hirsch et al., 2000). Blood specimens should be obtained for resistance testing before the failing drug regimen is stopped (Hirsch et al., 2000).