BC is a 32 year old male who presents to your HIV clinic for initiation of antiretroviral therapy (ART). He reports a sulfa allergy (Stevens-Johnson Syndrome) and his past medical history that includes recent HIV diagnosis and hypertension. He is currently taking lisinopril 20 mg daily. Listed below are his most recent labs:
Sodium: 141 mEq/L
Potassium: 3.8 mEq/L
Chloride: 108 mmol/L
Calcium: 9.2 mg/dL
CO2: 23 mmol/L
BUN: 13 mg/dL
SCr: 0.7 mg/dL
Glucose: 98 mg/dL
HIV RNA: 421,739
Which of the following would be most appropriate for initial ART therapy for this patient?
D. Isentress + Descovy
Answer with rationale:
The correct answer is D.
First line ART regimens for most patients include 3 drugs, most commonly an integrase strand transfer inhibitor (INSTI) in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). There is however a 2-drug combination tablet, Dovato (dolutegravir/lamivudine), that can be used first line with certain exceptions. Dovato is not a recommended initial regimen in patients with HIV RNA >500,000 copies/mL, hepatitis B virus (HBV) coinfection, or if antiretroviral treatment is going to be started before the results of genotypic resistance testing for reverse transcriptase or HBV testing are available.
Triumeq is a single combination tablet that contains abacavir, dolutegravir, and lamivudine and a first line agent for initial ART. Because Triumeq contains abacavir, patients must be screened for HLA-B*5701 allele prior to initiation. Patients who carry the HLA-B*5701 allele are at much higher risk of severe hypersensitivity reactions, and should not receive any abacavir-containing products. Because this patient tested positive for the HLA-B*5701 allele, Triumeq is contraindicated, making answer A incorrect.
When used alone, Truvada (emtricitabine/tenofovir disoproxil fumarate) is only FDA-approved for pre-exposure prophylaxis (PrEP), making answer B incorrect. However, it is used first line in combination with other agents, such as dolutegravir or raltegravir. When used for PrEP, Truvada should be avoided in patients with a CrCl < 60 mL/min. It should be noted that this recommendation for Truvada differs from Descovy (emtricitabine/tenofovir alafenamide). Adverse effects associated with tenofovir disoproxil fumarate include nephrotoxicity and decreased bone mineral density.
While it may be used as initial ART in certain situations (not first line), Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) is usually recommended as an alternative due to some of the tolerability issues and side-effect profile. This patient is also not a good candidate for Symtuza because of his sulfa allergy. Darunavir contains a sulfa moiety, so it should be generally avoided in with patients with a sulfa allergy, making answer C incorrect. Additionally, darunavir is a protease inhibitor, which is associated with gastrointestinal adverse effects (nausea, vomiting, diarrhea), metabolic complications (increased lipids, increased glucose), and fat redistribution.
Isentress (raltegravir) in combination with Descovy (emtricitabine/tenofovir alafenamide) is a recommended first line agent, making answer D correct. Isentress is an INSTI that is approved for treatment of HIV in combination with other agents. It is important to note that chelation can occur with polyvalent cations, so they should be avoided if possible. Otherwise, administer raltegravir 2 hours before or 6 hours after administration of the polyvalent cations. Descovy recently FDA-approval for PrEP and although it can also cause renal toxicity, it is less common because tenofovir alafenamide is associated with lower extracellular and higher intracellular concentrations compared to tenofovir disoproxil fumarate (TDF). Thus, there are lower plasma concentrations with tenofovir alafenamide and therefore lower rates of toxicity compared to TDF. Descovy is not recommended in patients with a CrCl < 30 mL/min.
We will have one more question next week before the Christmas break. Pray you have some great time off and are able to rest before we hit the ground running in 2021!