HIV Resistance Testing in Clinical Practice: A QALY-fied Success

• Drug resistance, microbial
• Human immunodeficiency virus
• Human immunodeficiency virus infections
• Antiretroviral therapy, highly active

Despite the significant advances in HIV therapy over the past 5 years, failure of highly active antiretroviral therapy (HAART) remains a significant problem. In a meta-analysis of 21 treatment groups from randomized clinical studies, only 46% of patients were able to reach the targeted HIV RNA viral load (<50 copies/mL) by 48 weeks (1). Because of virologic rebound or toxicity, the initial regimen ultimately fails even in most patients who are at first treated successfully. Therefore, HAART failure is common and should be anticipated by all clinicians caring for HIV-infected patients.

The management of HAART failure depends on the reason for failure and the availability of alternative therapies. The most common causes of HAART failure are difficulties in adherence, short-term intolerance, long-term toxicities (such as lipodystrophy, insulin resistance, and hyperlipidemias), insufficient drug levels, and development of virologic resistance. Management of adherence and treatment-related toxicities involves detailed discussions with the patient and identification of an acceptable new regimen. Evaluation of insufficient drug levels is challenging and requires formal pharmacologic testing, a procedure not available in most clinical settings.

The determination of virologic resistance is also a challenge. In the past, when viral resistance was suspected, it was assumed that resistance had developed to all drugs in the failing regimen (2); similarly, it was assumed that the virus would still be susceptible to drugs not previously used. Unfortunately, the strategy of designing new regimens that contain “virgin” agents while avoiding drugs used in previous regimens is often unsuccessful (3), mostly because the virus frequently does not become resistant to all of the drugs in the failing regimen and some “virgin” drugs may not be effective because of cross-resistance.

With the availability of resistance testing, clinicians can now determine more precisely which drugs the …