Stribild, a Single Tablet Regimen for the Treatment of HIV Disease

Cynthia Brinson 0 0 C. Brinson (&) Central Texas Clinical Research , Austin, TX, USA Introduction: In August 2012, the US Food and Drug Administration (FDA) approved a new single tablet once-a-day therapy for treatmentnave HIV patients. The new tablet contains emtricitabine and tenofovir disoproxil fumarate as well as elvitegravir and cobicistat, a pharmacokinetic enhancer which prolongs the effect of elvitegravir. The new tablet (EVG/ COBI/FTC/TDF), known as Stribild (Gilead Sciences, Foster City, CA, USA), is now the only FDA-approved single-tablet, once-daily, HIV medication that is composed of an integrase-inhibitor-based regimen. Methods: Stribild has been tested in two randomized double-blind phase 3 clinical trials with 1,408 patients who had not been previously treated for HIV. In one trial, Stribild was compared to the single-tablet regimen gold standard medication known as Atripla (Gilead Sciences, Foster City, CA, USA) that contains efavirenz, emtricitabine and tenofovir disoproxil fumarate (EFV/FTC/TDF). In the second clinical trial, Stribild was compared to another preferred treatment regimen of ritonavir-boosted atazanavir (ATV/RTV) with coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF, marketed as Truvada ; Gilead Sciences, Foster City, CA, USA). Results: The outcomes of the two recently published trials at 48 weeks indicated that Stribild was noninferior to both of the standard treatment regimens in controlling viral load. In the Stribild versus Atripla trial, 305 of 348 patients (87.6%) on Stribild versus 296 of 352 patients (84.1%) on Atripla had an HIV ribonucleic acid (RNA) concentration of \50 copies/mL at week 48. In the Stribild versus ATV/RTV with Truvada trial, 316 of 353 patients (89.5%) on Stribild versus 308 of 355 patients (86.8%) on Atripla had an HIV RNA concentration of \50 copies/mL at 48 weeks. Conclusion: Stribild had a favorable safety profile in the two recently published - randomized, double-blind, phase 3 clinical trials. With the approval of Stribild, clinicians now have more flexibility in prescribing singletablet regimens for patients. Since the mid-1990s, a number of advances have improved treatment efficacy as well as ease of administration in HIV. The current standard of care for treatment-nave patients is a combination of at least three active medications chosen from two or more different classes of antiretroviral drugs, which can help reduce HIV-associated morbidity and mortality, and prevent transmission of the infection [1]. International guidelines recommend that patients not previously treated for HIV receive the nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate combined with a third medication: one of the ritonavir-boosted protease inhibitors (atazanavir or darunavir); the integrase inhibitor raltegravir; or the nonnucleoside reverse transcriptase inhibitor efavirenz [2]. Until recently, only one of these preferred regimens was formulated into a single tablet with efavirenz, emtricitabine and tenofovir disoproxil fumarate (EFV/FTC/TDF), marketed as Atripla (Gilead Sciences, Foster City, CA, USA). Clinical trials have shown this tablet to have high efficacy, ease of administration and safety. The regimen has thus become widely used and is considered a gold standard for current practice [36]. However, not all patients can tolerate Atripla since it can cause central nervous system (CNS) side effects, rash and hyperlipidemia [5, 6]. It also may increase the risk of teratogenicity during pregnancy when administered during the first trimester [7, 8]. Thus, the addition of the newly US Food and Drug Administration (FDA)-approved single tablet HIV therapy for treatment-nave patients known as Stribild (Gilead Sciences, Foster City, CA, USA) is a welcome development. The Stribild single-tablet regimen contains emtricitabine and tenofovir disoproxil fumarate plus elvitegravir and cobicistat (EVG/COBI/ FTC/TDF), a pharmacokinetic enhancer, which prolongs the effect of elvitegravir. Known in clinical studies prior to approval as the Quad, the new single-tablet regimen was approved by the FDA in August 2012. The purpose of this review is to discuss the efficacy, safety outcomes and side effects of Stribild as seen in two randomized double-blind phase 3 clinical trials, particularly when compared to Atripla and the treatment regimen of ritonavir-boosted atazanavir (ATV/ RTV) (Norvir ; AbbVie Inc., North Chicago, IL, USA) plus emtricitabine and tenofovir disoproxil fumarate (Truvada ; Gilead Sciences, Foster City, CA, USA) in treatment nave HIV patients [9, 10]. The article will also provide current data on the efficacy of Stribild and its component medications, information on Stribilds side effects and perspective on which HIV patients might benefit from this new single-tablet regimen HIV medication. The two randomized, double-blind phase 3 noninferiority clinical trials of Stribild, which were the basis for the medications recent approval by the FDA, studied its use in 1,408 adult patients not previously treated for HIV. In the first clinical trial, Stribild was compared to Atripla over 48 weeks. The second phase 3 trial measured outcomes with Stribild compared to ATV/RTV and Truvada taken once daily, also over 48 weeks [9, 10]. The results of both trials indicated that Stribild had high efficacy in controlling viral load and good tolerability over 48 weeks. It was shown to be noninferior when compared to the two different current HIV treatments and in some cases, had a more favorable side-effect profile [9, 10]. In the phase 3 clinical trials, Stribild treatment resulted in fewer abnormal dreams, less dizziness, insomnia and rash than, for example, Atripla, but an increase in nausea was observed. Stribild also resulted in fewer cases of abnormal liver function than ATV/ RTV plus Truvada and had smaller median increases in fasting cholesterol concentrations. However, a greater increase in serum creatinine was seen with Stribild than with Atripla [9, 10]. Stribild is now the only FDA-approved single-tablet regimen HIV medication that is composed of an integrase-inhibitor-based therapy. It is a highly effective alternative therapy for treatment-nave HIV patients, which provides clinicians with greater flexibility in prescribing medications, without sacrificing ease of use for patients. A MEDLINE search was performed using the key words elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate to identify relevant articles for inclusion in this review. Two randomized, double-blind phase 3 trials of Stribild, containing EVG/COBI/FTC/TDF, were identified. In the clinical trials, outcomes with Stribild were compared to those with two other recommended HIV drug regimens. In one clinical trial, Stribild was compared to the once-daily tablet Atripla. In the other trial, outcomes with Stribild were compared to those with the treatment regimen of A (...truncated)