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Assessing and managing a patient who is experiencing antiretroviral therapy (ART) failure can be complex. Expert advice can be critical and should be sought in many instances.
Evaluation of virologic failure should include an assessment of adherence, drug-drug and drug-food interactions, drug tolerability, HIV RNA level and CD4 T lymphocyte (CD4) cell count trends over time, ART history, and prior and current drug-resistance test results.
Drug-resistance testing should be performed while the patient is taking the failing antiretroviral (ARV) regimen or within 4 weeks of treatment discontinuation. If more than 4 weeks have elapsed since ARV drugs were discontinued, resistance testing can still provide useful information to guide therapy, although it may not detect previously selected resistance mutations.
The goal of treatment for ART-experienced patients with drug resistance who are experiencing virologic failure is to establish suppression (that is, HIV RNA levels below the lower limits of detection of currently used assays).
A new regimen can include two fully active ARV drugs if at least one with a high resistance barrier is included (e.g., dolutegravir or boosted darunavir). If no fully active drug with a high resistance barrier is available, then every effort should be made to include three fully active drugs.
In general, adding a single ARV agent to a virologically failing regimen is not recommended, because this would rarely result in full viral suppression and, therefore, may risk the development of resistance to all drugs in the regimen.
For some highly ART-experienced patients with extensive drug resistance, maximal virologic suppression may not be possible. In this case, ART should be continued with regimens that are designed to minimize toxicity, preserve CD4 counts, and delay clinical progression.
When it is not possible to construct a viable suppressive regimen for a patient with multidrug-resistant HIV, the clinician should consider enrolling the patient in a clinical trial of investigational agents or contacting pharmaceutical companies that may have investigational agents available.
In patients with virologic failure, it is crucial to provide continuous adherence support before and after ARV regimen changes.
When switching an ARV regimen in a patient with hepatitis B virus (HBV)/HIV coinfection, ARV drugs that are active against HBV should be continued as part of the new regimen. Discontinuation of these drugs may lead to the reactivation of HBV, which may result in serious hepatocellular damage.
Discontinuing or briefly interrupting therapy may lead to a rapid increase in HIV RNA, a decrease in CD4 count, and an increase in the risk of clinical progression. Therefore, this strategy is not recommended in the setting of virologic failure.