HIV update: Which single-tablet regimens, and when

Raltegravir plus tenofovir disoproxil fumarate/emtricitabine (Isentress plus Truvada). The combination of the integrase inhibitor raltegravir plus fixed-dose tenofovir disoproxil fumarate and emtricitabine has been recommended by the DHHS as first-line therapy for approximately 5 years. The recommendation is based mainly on data from the STARTMRK trial, a phase III non-inferiority trial that followed more than 500 patients for 5 years and concluded that raltegravir/tenofovir/emtricitabine has superior efficacy with fewer drug-related adverse effects than efavirenz/tenofovir/emtricitabine.¹⁹ The overall pill burden with this regimen is 3 tablets per day. Although highly effective, the main drawbacks of raltegravir are that it must be dosed twice daily (which may be less preferable if adherence is a concern) and the genetic barrier to resistance is lower than that of the other 2 approved integrase inhibitors. There is a once-daily formulation of raltegravir that's expected to be available late in 2017.²⁰

Before starting a regimen with abacavir, screen patients for the HLA-B*5701 allele, which predicts hypersensitivity to the drug.Adverse effects and toxicities (except the renal and bone effects due to tenofovir disoproxil fumarate mentioned earlier) and drug interactions with this regimen are infrequent. Raltegravir can be taken with or without food. Concurrent use of antacids that contain aluminum or magnesium may reduce absorption of raltegravir and so should be avoided.²¹

PI-based regimen

Darunavir (Prezista) and ritonavir (Norvir) plus tenofovir disoproxil fumarate/emtricitabine (Truvada). PIs were once the key component of all ART regimens; however, boosted darunavir is now the only PI-based regimen currently recommended as first-line therapy. It is taken as 3 tablets once daily. If the co-formulation with cobicistat is used, just 2 tablets daily are required. One advantage with darunavir with either of the boosting agents is that it does not appear to cause insulin resistance or dyslipidemia as occurs with older PIs, such as indinavir and lopinavir.² The boosting agents do, however, increase the likelihood of drug-drug interactions. As with all PIs, darunavir has a very high genetic barrier to resistance, which is important in patients for whom adherence is a concern.

Adverse effects of the PIs may include nausea, vomiting, and diarrhea, all of which are typically mild and self-limiting.²² Co-formulation of darunavir with cobicistat, tenofovir alafenamide, and emtricitabine is in phase III studies. Projected to be available in late 2017, it will provide yet another daily STR option.²³

The addition of fixed-dose tenofovir alafenamide/emtricitabine

In July 2016, the DHHS panel made some additions to their guidelines to reflect the FDA approval of 3 fixed-dose combination products that contain tenofovir alafenamide. Specifically, the combination of tenofovir alafenamide and emtricitabine is recommended for use with the integrase inhibitors—dolutegravir or raltegravir. It is also recommended in combination with ritonavir-boosted darunavir.