How is antiretroviral therapy selected in treatment-experienced patients with HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

Answer

Antiretroviral activity and durability improves with the addition of fully active agents in a regimen.  Ideally, regimens should include at least 2 or, optimally, 3 fully active agents. The selection of individual agents should be based on the antiretroviral treatment history, genotypic and/or phenotypic resistance results, drug-drug interaction potential, and medication intolerance, with the goal of maximizing antiviral activity and adherence.

Divergence from the strategy of using 2 NRTIs with either an INSTI, NNRTI or a PI is typically necessary as the extent of drug resistance increases. It is not uncommon to include 4 to 6 antiretrovirals in a regimen for a patient with extensive drug resistance in order to increase the degree of activity. [8]

The introduction of new antiretroviral agents has broadened the number of active agents available for treatment of patients with infection due to resistant HIV and has improved the success rate of therapy. Limited information exists regarding optimal combinations of agents for treatment, as selection is often based on resistance testing results, prior treatment history, and intolerance. [8]

Enfuvirtide is highly effective in the treatment of antiretroviral therapy–experienced patients but requires subcutaneous injection twice daily and is associated with injection-site reactions.

Darunavir and tipranavir typically retain activity in the presence of multiple protease inhibitor mutations. However, the use of tipranavir has been hindered by the potential for interaction with other antiretroviral agents, hepatotoxicity, and reports of intracranial bleeding events.

Etravirine is considered a second-generation NNRTI and is most effective when combined with other active agents but may cause drug-drug interactions with other antiretroviral agents.

Dolutegravir and bictegravir can possibly be used in the setting of raltegravir and elvitegravir resistance, though administration may need to be increased to twice daily.

The role of maraviroc in patients with extensive drug resistance has been limited because of the high frequency of dual/mixed-tropic or CXCR4-tropic virus in patients with more longstanding HIV infection and the necessity for expensive tropism assay pretesting.


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