Drug Interactions
Drug interactions should be a consideration for all patients with an extensive review of their current medications. Pharmaco-enhancers or “boosting agents,” such as ritonavir or cobicistat, are used to increase drug levels of HIV medications. However, since this is accomplished by inhibition of CYP3A there is great potential for interaction with other medications; opiates, amphetamines, sildenafil, most lipid-lowering agents, and numerous other drugs have significant interactions with ritonavir and cobicistat. Looking at current medications may not be enough; some consideration should be made for the potential of adding medications. For example, if a patient has a seizure disorder and is not well controlled on levetiracetam, consideration should be made if there could be a potential need for phenytoin or other agent that commonly interacts with some HIV medications.
Adverse Events
Adverse events (AEs) are a large consideration when choosing ARV therapy (ART) and can either have medical implications or be patient-specific. Some agents have severe AEs like worsening depression and suicidal ideation. Others are less severe and a particular patient may prefer a risk for gastrointestinal (GI) AEs rather than insomnia.
Adherence
Predicting adherence is difficult; however, certain factors may predispose a patient to being less adherent, including active substance abuse, depression or other mood disorder, unstable housing, and inconsistent access to food. Some regimens are more forgiving and require a lower level of adherence and are less likely to have resistance mutations with failure. Both ritonavir-boosted PIs, as well as dolutegravir, seem to have the best outcomes with lower levels of adherence. Tailoring the dosing and food requirements to a patient’s lifestyle can also improve adherence.
Childbearing Age
Pregnancy and potential for pregnancy must be considered in all female patients. Although pregnancy is beyond the scope of this discussion, the perinatal guidelines should be considered in women of childbearing age. 3
Custom A Regimen
Convenience is a major consideration when selecting a regimen. Comparator studies done to demonstrate regimen efficacy using intention-to-treat structures highlight this point. Many patients express that a single tablet is their most important priority. Other important considerations for regimen selection are food requirements or restrictions, and whether there are drug coadministration concerns (eg, divalent cations in antacids or vitamins). These will be discussed more with each
individual ARV agent.
Now that regimen considerations have been reviewed from both provider and patient perspectives, we will focus on the individual classes of ARVs to make selection of a regimen more tailored to patient needs.
The NNRTI Class
The NNRTI class has 2 first-line “recommended” agents, efavirenz and rilpivirine, which are both conveniently available as “one-pill-a-day” coformulated regimens with tenofovir and emtricitabine. 1 While the 2 NNRTIs are in the same class, they each have unique properties that would lead a clinician to choose one versus the other.
Efavirenz is the only NNRTI recommended to be paired with abacavir and lamivudine (coformulated as Epzicom) first-line nucleosides. However, it is only recommended to be used in patients with VL < 100,000 copies/mL.
Efavirenz is one of the most studied and widely used ARV. Efavirenz/emtricitabine/tenofovir (coformulated as Atripla) was the first once daily regimen and has shown noninferiority or superiority to most ARV regimens. However, AEs are the most common reason for discontinuation. Efavirenz is well known for its CNS AEs, including vivid dreams, somnolence, impaired concentration, headaches, and depression. These AEs typically diminish or abate after several weeks of therapy. However, certain CNS effects may be long term, including depression or suicidal thoughts.