The first-line PIs are better tolerated than other PIs. Gastrointestinal AEs are still common. Scleral icterus and moderate to severe jaundice occur in 5% to 9% of patients taking atazanavir due to inhibition of the indirect metabolism of bilirubin. 8 As a sulfa-related drug, darunavir is generally avoided if the patient has a sulfa allergy, but can be used with caution. 9 Another limitation for PIs is that both options are required to be taken with food.
Protease inhibitors will always have a place in treatment-experienced patients with drug resistance, but may have a unique role in patients with baseline M184V mutations. A retrospective analysis showed that patients with a M184V mutation alone achieved equivalent viral suppression if the patient was on 3 fully active HIV ARVs or on a boosted PI, lamivudine or emtricitabine, and 1 additional NRTI. 10 Patients with only a M184V mutation can still achieve full suppression without adding an additional ARV agent or using 3 HIV drug classes, preserving future treatment options. Boosted-PI regimens have less drug resistance at failure than NNRTI-based regimens. Less than 5% of new infections have baseline (pretreatment) drug resistance to PIs. 6
Boosted PIs have a long clinical history and are still appropriate for many treatment-naive and experienced patients. Reduced pill burden with cobicistat formulation may revive utilization when the pill burden decreases from 3 tablets per day to 1 or 2.
Integrase Strand Inhibitors
INSTI-based regimens have had low discontinuation rates overall in clinical trials, and are great options for a majority of patients. There are 3 INSTIs, all of which are on the list of preferred agents according to the DHHS guidelines. INSTIs may be used with any baseline VL or CD4 counts, without concern for potency. Each of the 3 agents has clear benefits and disadvantages when choosing among them.
Raltegravir has no food requirements and has the least amount of drug interactions of nearly all ART regimens since it is not processed via cytochrome P450 enzymes, but it is dosed twice daily. When paired with emtricitabine/tenofovir, it is also the preferred regimen for occupational postexposure prophylaxis.
Dolut egr avi r i s onc e da i ly, ha s no food requirements, and also avoids drug interactions due to cytochrome P450 enzymes. However, this ARV agent does inhibit the renal organic cation transporter, so some clinically relevant interactions exist. Dolutegravir also has the benefit of being paired with either emtricitabine/tenofovir or abacavir/lamivudine, both of which are preferred DHHS regimens. As mentioned previously, dolutegravir/abacavir/lamivudine are now coformulated
and are an additional all-in-one option. Abacavir has conflicting data regarding increased risk for myocardial infarction; this risk should be considered in light of other risk factors for the patient including age, diabetes, etc. 11
Elvitegravir is unique as an INSTI. Elvitegravir/cobicistat/emtricitabine/tenofovir must be administered with food and since it utilizes cobicistat as a pharmaco-enhancer to boost elvitegravir’s levels, there are a significant number of potential drug interactions. Cobicistat-containing regimens must not be prescribed for patients with a baseline CrCl <70 mL/min. 2