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Although treatment with an INSTI-based regimen is currently the standard of care recommended by US and European guidelines, all of the guidelines suggest regimens for those patients for whom INSTI treatment is not advised. Although transmitted resistance to INSTIs is still rare, there may be other situations in which INSTI-based ART may not be optimal for a given patient. For example, a small proportion of patients started on INSTI-containing regimens have central nervous system adverse events (headache, insomnia, irritability) that prompt the need for an alternative treatment. Some clinicians may choose efavirenz/emtricitabine/tenofovir DF if a patient has concomitant tuberculosis, as there are more data for use of this combination in tuberculosis-coinfected individuals. Another option is the next-generation NNRTI doravirine, which was recently approved by the FDA for use in combination with other ARVs and coformulated as a fixed-dose, single-tablet regimen with lamivudine and tenofovir DF for treatment-naive adults.[78,79] Because no clinically important interactions have been observed between doravirine and the proton pump inhibitor pantoprazole or an aluminum–magnesium antacid, doravirine-based ART may be preferred in patients requiring these drugs.
Based on the above considerations, ART with NNRTIs or boosted PIs may be better options in some settings. The following sections will outline data that support other options and discuss what factors should be considered when choosing these options.