HIV update: Which single-tablet regimens, and when

INSTI-based regimens

Dolutegravir/abacavir/lamivudine (Triumeq). Approved by the FDA as a single-tablet regimen in 2014, the combination of dolutegravir/abacavir/lamivudine has proven to be highly effective and well-tolerated in many clinical trials.^6-9 However, before this regimen is started, patients must be screened for the HLA-B*5701 allele, which predicts hypersensitivity to abacavir.¹⁰ Assessing patients’ risk for cardiovascular disease is also advised because some data suggest that abacavir may increase the risk of cardiovascular events, although this remains controversial.²

Most of the newer agents are more potent, less toxic, have a higher genetic barrier to resistance, and a longer half-life than their predecessors.Dolutegravir is generally well-tolerated with minimal adverse effects (≥2% incidence of headache and insomnia) and toxicity.¹¹ Dolutegravir/abacavir/lamivudine should be taken 2 hours before or 6 hours after taking antacids or laxatives, sucralfate, and oral supplements with iron or calcium. However, it may be taken with calcium or iron supplements if it is also taken with food.¹¹ Dolutegravir increases levels of metformin about 2-fold, so patients should not take more than 1000 mg/d of this oral hypoglycemic agent.¹¹

Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (Tivicay plus Truvada). The combination of dolutegravir plus fixed-dose tenofovir disoproxil fumarate and emtricitabine is administered as 2 pills per day. Because tenofovir disoproxil fumarate can cause proximal renal tubular dysfunction, phosphate wasting, and decreased bone mineral density (BMD), avoid prescribing it for patients with underlying renal dysfunction (creatinine clearance [CrCl] <50 mL/min) and prescribe it cautiously for patients with hypertension or diabetes who are at increased risk of renal disease. Emtricitabine is generally safe and well tolerated, but the dose should be reduced in patients with renal insufficiency, which would preclude the use of this fixed-dose combination.¹²

Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (Genvoya). The newer 4-drug combination of elvite­gravir/­­cobicistat/tenofovir alafenamide/emtricitabine­­ that was approved by the FDA in November 2015,¹³ contains the more recently approved form of tenofovir, which can be used in patients who have a CrCl as low as 30 mL/min. Compared to formulations containing tenofovir disoproxil fumarate, the newer tenofovir alafenamide formulation achieves higher intracellular levels in CD4 lymphocytes (but not in renal tubular cells). This allows for a lower dose of the drug and a smaller tablet size with co-formulation. It does not appear to cause kidney problems or loss of BMD as can be seen with tenofovir disoproxil fumarate.¹⁴ This newer single-tablet regimen may be best suited for older patients with HIV or those with comorbidities such as hypertension or diabetes.

Elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine (Stribild). The FDA approved the combination of elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine as a single-tablet regimen in 2012. The integrase inhibitor, elvitegravir, requires boosting with the CYP3A inhibitor, cobicistat, and should be taken with food.¹⁵ Two clinical trials demonstrated the superior efficacy of elvitegravir compared to a boosted PI and NNRTI-based regimen.^16,17 Elvitegravir is generally well tolerated, but sometimes causes dyspepsia, nausea, or diarrhea.¹⁵ Similar to dolutegravir, it should not be taken concurrently with certain supplements—in this case, those containing aluminum, calcium, iron, magnesium, or zinc.¹⁵ Because it contains tenofovir disoproxil fumarate as an active agent, it should not be used in patients with a CrCl of <70 mL/min.¹⁵

Cobicistat inhibits tubular secretion of creatinine, so it may produce an elevation in serum creatinine without actually affecting glomerular function. Cobicistat may also cause drug-drug interactions with certain antiarrhythmics, sedative-hypnotics, and erectile dysfunction agents, and is contraindicated with some statins, anticonvulsants, and ergot derivatives.¹⁸