New quad pill for HIV

Elvitegravir, cobicistat, emtricitabine, tenofovir (Stribild—Gilead)

Treatment-naive patients with HIV-1 infection can now benefit from the convenience of a single tablet taken once daily to manage a disease that was once filled with complicated medication regimens and heavy pill burdens. The first and only four-drug, dual-target combination tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir 300 mg (—Gilead) has been approved by FDA for the management of HIV-1 infection in treatment-naive adults. Elvitegravir and cobicistat are novel agents that have not been approved previously as standalone agents or in other combination tablets. This simplified regimen may enhance adherence rates and reduce the potential for resistance in those who fail to take their HIV regimens as prescribed.

Clinical data

Approval of the quad pill was based on data from two Phase III trials involving 1,408 treatment-naive adult patients. The trials were designed to measure the percentage of patients who had an undetectable amount of HIV in their blood (i.e., HIV-1 RNA < 50 copies/mL) at 48 weeks compared with efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg (—Gilead) and a regimen containing ritonavir-boosted atazanavir emtricitabine 200 mg/tenofovir 300 mg (—Gilead).

After 48 weeks, results showed that between 88% and 90% of patients treated with Stribild had an undetectable amount of HIV in their blood, compared with 84% treated with Atripla and 87% treated with ritonavir-boosted atazanavir Truvada. A similar percentage of patients across the two studies in all groups experienced virologic failure or discontinued study drug as a result of adverse events.

Most adverse events were mild to moderate, with nausea (16%), diarrhea (12%), abnormal dreams (9%), headache (7%), and fatigue (5%) being common events. Gilead is required to conduct additional studies to evaluate resistance and drug interactions and to help further characterize the drug’s safety in women and children.

Cost concerns

According to an article in Forbes, the annual cost for this combination is anticipated to be approximately $28,500. This high cost has prompted some HIV activists to take action to find a way to lower the cost. The magazine noted that the AIDS Healthcare Foundation is angling to place a referendum in front of San Francisco voters to require city officials to hold talks with drug makers about pricing for essential medicines.

Elvitegravir, cobicistat, emtricitabine, tenofovir (Stribild)

Manufacturer: Gilead

Drug class: An integrase strand transfer inhibitor, a pharmacokinetic enhancer, and two nucleos(t)ide analog HIV-1 reverse transcriptase inhibitors

Indication: Treatment of HIV-1 infection in treatment-naive adult patients

Dosage: One tablet taken once daily with food

  • Patients with a creatinine clearance (CrCl) of less than 70 mL/min should not be given this therapy. If CrCl levels fall below 50 mL/min during treatment, therapy should be discontinued.

Of note: The labeling has a boxed warning for lactic acidosis/severe hepatomegaly with steatosis because these adverse events have been reported with the use of nucleoside analogs such as tenofovir in combination with other antiretrovirals.

  • The labeling also has a boxed warning for post-treatment acute exacerbation of hepatitis B; hepatic function should be monitored closely for at least several months in patients coinfected with hepatitis B and HIV who discontinue therapy.
  • A list of drugs that are contraindicated in patients prescribed this therapy are reviewed in the label.
  • In addition to the boxed warnings, other warnings and precautions include new onset or worsening renal impairment, avoidance of other antiretroviral therapies, decreases in bone mineral density, fat redistribution, and immune reconstitution syndrome.

Patient counseling

Educate patients about proper administration and storage, the potential for numerous drug interactions, and the various adverse events associated with therapy. Explain to patients that the tablets must be taken with food at the same time each day and that missed doses should be taken as soon as they remember unless it is time for the next dose.