HIV Drugs: What's New?

As HIV/AIDS research continues and more drugs are developed to improve patient compliance and quality of life, it is important for specialty pharmacists to understand the drugs that will soon be making an impact on the lives of their patients.
 
Latest Antiretroviral Approvals

The latest antiretroviral drug, Tibotec Therapeutics’ Edurant (rilpivirine), was approved by the FDA in May 2011 for use in combination with other antiretroviral agents for the treatment of HIV-1 infection for treatment-inexperienced adults. The nonnucleoside reverse transcriptase inhibitor (NNRTI), which is available in a once-daily 25-mg tablet, should be taken with food to increase absorption. Acid reducing agents such as antacids and H₂ receptor antagonists should be used with caution, as these may decrease Edurant’s levels in the blood. The drug is contraindicated with the co-administration of cytochrome P450 (CYP) 3A enzyme inducers such as proton pump inhibitors and certain anticonvulsants, because these can also decrease Edurant’s blood levels.¹

In clinical trials, patients taking Edurant who had HIV viral loads greater than 100,000 copies/mL experienced more treatment failures than those taking efavirenz, a commonly used NNRTI.  These failures to reduce viral load conferred cross-resistance to other NNRTIs more commonly in the Edurant group. Otherwise, the 2 drugs achieved similar levels of efficacy. When compared, the 2 drugs were associated with similar rates of depression, but subjects treated with Edurant reported fewer instances of dizziness, abnormal dreams, and rash.¹

Rilpivirine is a component of the new all-in-1 combination pill Complera from Gilead Sciences and Tibotec Therapeutics. The once-daily tablet also contains the well-established nucleoside reverse transcriptase inhibitor (NRTI) backbone of emtricitabine/tenofovir disoproxil fumarate, and it was approved by the FDA August 2011. The tablet is taken once daily with meals.² The warnings associated with each of its individual components should be considered prior to use.

Emerging HIV Therapies

In terms of drugs in the pipeline, the FDA accepted a New Drug Application in December 2011 for Gilead's once-daily 4-drug combination pill known as the “Quad.” The all-in-1 HIV regimen contains emtricitabine/tenofovir disoproxil fumarate in combination with 2 investigational drugs being developed by Gilead: elvitegravir and cobicistat.³

Elvitegravir is a once-daily integrase inhibitor, which stops HIV replication by preventing the virus from incorporating into the DNA of human cells. When used in combination with other antiretroviral agents, elvitegravir, boosted by Norvir (ritonavir), has been shown to be noninferior to twice-daily raltegravir, another integrase inhibitor, at suppressing HIV activity. ⁴

Cobicistat, like the protease inhibitor (PI) Norvir (ritonavir), is a potent inhibitor of the CYP3A enzyme and is used to boost the levels of other antiretroviral drugs by preventing their breakdown. Cobicistat, however, has no anti-HIV activity on its own.⁵ In a clinical trial, a cobicistat-boosted PI-based regimen compared well with a Norvir-boosted PI-based regimen. In addition to being part of the “Quad” pill, cobicistat is also being investigated as a standalone booster for use with other antiretroviral drugs.⁶

If approved, the “Quad” pill will be the third all-in-1 HIV pill after Bristol-Myers Squibb’s and Gilead's Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) and Complera (rilpivirine/emtricitabine/tenofovir disoproxil fumarate).⁷ In Phase 3 clinical trials, the “Quad” tablet demonstrated comparable efficacy with Atripla and Norvir-boosted Reyataz (atazanavir/Truvada) in achieving viral suppression and increasing CD4 cell counts after 24 and 48 weeks.^8,9

Today, HIV and AIDS patients are living longer, healthier lives with the help of antiretroviral therapy. With the high cost, complicated regimens, and great need for compliance associated with HIV/AIDs treatment, it's easy to see how specialty pharmacists can play a role in managing the disease state of this population.

Current and Emerging HIV Therapies

Trade Name (Generic Name)	Class	Status	Dosing
Edurant (rilpivirine)	NNRTI	Approved  May 2011	1 tablet/day, part of a multidrug regimen
Complera (rilpivirine/emtricitabine/ tenofovir disoproxil fumarate)	NNRTI/NRTI/NRTI	Approved  Aug 2011	1 tablet/day
“Quad” (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate)	Integrase inhibitor/boosting agent/NRTI/NRTI	Awaiting FDA approval	1 tablet/day
Elvitegravir	Integrase inhibitor	Phase 3 trials	1 tablet/day, part of a multidrug regimen
Cobicistat	Boosting agent	Phase 3 trials	Part of a multidrug regimen

NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor.
References

1. Edurant (rilpivirine) tablets [package insert]. Raritan, NJ: Tibotec Therapeutics; 2011.
2. Approval of Complera: emtricitabine/rilpivirine/tenofovir DF fixed dose combination [Internet]. Silver Spring: U.S. Food and Drug Administration; c2012 [updated 2011 Aug 10; cited 2012 Jan 27]. Department of Health and Human Services. Available from: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm267592.htm
3. U.S. FDA Accepts New Drug Application for Gilead's Once-Daily, Single-Tablet Quad HIV Regimen [Internet]. Foster City: Gilead; c2012 [updated 2011 Dec 23; cited 2012 Jan 27]. Available from: http://www.gilead.com/pr_1324679432
4. Elvitegravir [Internet]. Rockville: AIDSinfo; c2012 [updated 2011 Aug 30; cited 2012 Jan 27]. Department of Health and Human Services. Available from: http://aidsinfo.nih.gov/drugs/421/elvitegravir/professional
5. Cobicistat [Internet]. Rockville: AIDSinfo; c2012 [updated 2010 Oct 3; cited 2012 Jan 27]. Department of Health and Human Services. Available from: http://aidsinfo.nih.gov/drugs/440/cobicistat/professional
6. Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS 2011;25:1881-1886.
7. Antiretroviral drugs used in the treatment of HIV infection [Internet]. Silver Spring: U.S. Food and Drug Administration; c2012 [cited 2012 Jan 27]. Department of Health and Human Services. Available from: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm
8. Gilead's Second Pivotal Phase 3 Clinical Study of the Investigational Antiretroviral Quad Regimen Meets 48-Week Primary Objective [Internet]. Foster City: Gilead; c2012 [updated 2011 Sep 19; cited 2012 Jan 27]. Available from: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=1608125
9. Gilead's Investigational Antiretroviral Quad Regimen Meets 48-Week Primary Objective in Pivotal Phase 3 Clinical Study 102 [Internet]. Foster City: Gilead; c2012 [updated 2011 Aug 15; cited 2012 Jan 27]. Available from: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=1596378