The recommendation of taking efavirenz regimens at bedtime on an empty stomach to reduce CNS AEs is not ideal for every patient. Efavirenz can also have additive CNS AEs with alcohol and potentially lead to blackouts. It can also lead to false positives for marijuana and benzodiazepines on drug screenings. The FDA classifies efavirenz as Pregnancy Category D, so it should be avoided in women of childbearing age. 4 However, if pregnancy isdetected while someone is taking efavirenz there is no need to discontinue the agent since the neural tube has formed by that time. 3
Rilpivirine is better tolerated than efavirenz, with fewer and less severe CNS AEs. Rilpivirine/emtricitabine/tenofovir (coformulated as Complera) has the convenience of being 1 pill once daily; however, it is not appropriate for all patients. It should be avoided in patients with a pretreatment VL > 100,000 copies/mL or CD4 < 200 cells/mm3. Patients with values beyond these thresholds were more likely to experience early virologic failure in the first months of therapy compared to efavirenz/emtricitabine/tenofovir. 5 Because it is a CYP3A4 substrate, rilpivirine has important drug-drug interactions. Proton pump inhibitors are contraindicated, and H2 receptor antagonists, like ranitidine or famotidine, require specific separation intervals, as do antacids and divalent cations. Another item of importance is that it should be administered with a meal.
The NNRTI class is plagued by its low genetic barrier to resistance, with a single mutation that may confer resistance to nearly all NNRTIs. Estimated transmitted HIV drug resistance at baseline in men who have sex with men can be 8% to 10%. 6 Transmitted resistance is a concern, a baseline genotype can determine if a patient is at a higher risk for virologic failure with NNRTIs.
Protease Inhibitors
Protease inhibitors have gone from the main stay of HIV treatment to being a less desirable first-line treatment option. Protease inhibitors have the highest pill burden and drug interactions of the first-line agents; they must be taken with food, and as of October 2014 there are no coformulated tablets (other than lopinavir/ritonavir which is not first-line). New combination tablets utilizing cobicistat as a boosting agent may resuscitate the use of the PIs. The coformulations under investigation are atazanavir/cobicistat, darunavir/cobicistat, and darunavir/cobicistat/emtricitabine/tenofovir alafenamide. These combinations will decrease the pill burden for PIs to 1 to 2 pill(s) a day instead of 3 pills a day. Although 1 to 3 pills taken once daily does not sound like a big difference, given a choice, the majority of patients choose the least number of pills.
How Does Cobicistat Compare With Ritonavir?
Cobicistat has no HIV activity and may be better tolerated than ritonavir. Effects on total cholesterol and triglycerides are similar between the 2 boosting agents. 7 Cobicistat causes a modest, rapid increase in serum creatinine (SrCr) through inhibition of tubular secretion without impact on the glomerular filtration rate. The coformulated product of cobicistat/elvitegravir is not recommended to be initiated in patients with CrCl < 70 mL/min at baseline. 2 It is anticipated that cobicistat-boosted PI regimens will have a similar limitation. The elevation of SrCr from cobicistat makes it difficult to monitor for tenofovir-related renal dysfunction since SrCr is no longer a reliable surrogate marker for renal function. 7 Cobicistat and ritonavir inhibit CYP3A4 and have almost identical drug interactions. However, only ritonavir interacts with methadone.