Various treatment options are now available for patients with HIV. The 3 newest FDA approvals—maraviroc, raltegravir, and etravirine—are reviewed here.
Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.
Currently, the classes of pharmacologicagents used in thetreatment of HIV include nonnucleosidereverse transcriptase inhibitors(NNRTIs), nucleoside reverse transcriptaseinhibitors (NRTIs), protease inhibitors(PIs), entry/fusion inhibitors, andintegrase inhibitors. In addition, variousagents are available, known as fixed-dosecombinations, that contain 2 ormore HIV medications that come fromone or more drug classes.1 In 2007,the FDA approved 2 new treatmentsfor HIV: maraviroc (Selzentry), manufacturedby Pfizer Inc, in August, andraltegravir (Insentress) manufactured byMerck & Co Inc, in October. In 2008,the FDA approved etravirine (Intelence),manufactured by Tibotec Therapeutics.This article will review the 3 recentlyapproved pharmacologic agents for thetreatment of HIV infection.
Maraviroc, in combination with otherantiretroviral agents, is indicated fortreatment-experienced adult patients infectedwith only chemokine receptor 5(CCR5)?tropic HIV-1 detectable who haveevidence of viral replication and HIV-1strains resistant to multiple antiretroviralagents.2 It is classified as a selective,slowly reversible, small molecule antagonistof the interaction between humanCCR5 and HIV-1 gp120.2 The blockingof this interaction prohibits CCR5-tropicentry into cells.1
The agent must be used in conjunctionwith other antiretroviral agents.According to manufacturer recommendations,the recommended dose of maravirocvaries based on which agent it willbe used in conjunction with due to druginteractions (Table).
Maraviroc may be taken without regardto food and is available in 150- and 300-mg tablets. The most commonadverse effects associated with the useof maraviroc twice a day include cough,pyrexia, upper respiratory tract infections,rash, musculoskeletal symptoms,abdominal pain, and dizziness.2 Otheradverse effects reported with once-adayand twice-daily dosing were diarrhea,edema, influenza, esophageal candidiasis,sleep disorders, rhinitis, parasomnias,and urinary abnormalities.1Pharmacists should remind patients toimmediately seek medical attention ifthey experience a rash, jaundice, darkurine, vomiting, or abdominal pain. Discontinuationof maraviroc should be consideredin any patient showing signs orsymptoms of hepatitis, or with increasedliver transaminases combined with rashor other systemic symptoms.2
Patients also should be remindedto adhere to the prescribed medicationregimen, and if a dose is missed,to take it as soon as possible. If themissed dose is remembered less than 6hours before the next scheduled dose,however, patients should not take themissed dose, but should wait and takethe next scheduled dose. Patients alsoshould be reminded to avoid driving oroperating machinery if they experienceany episodes of dizziness. Patients alsoshould be advised that the concomitantuse of maraviroc and St. John's wort, orproducts containing St. John's wort, is notrecommended. Maraviroc should notbe used in individuals younger than 16years of age and is classified by the FDAas pregnancy category B.2
Recommended Dosage and Administration
When given with strong CYP3A inhibitors (with or without CYP3A inducers), including PIs (except tipranavir/ritonavir), delavirdine
150 mg twice a day
With NRTIs, tipranavir/ritonavir, nevirapine, and other drugs that are not strong CYP3A inhibitors or CYP3A inducers
300 mg twice a day
With CYP3A inducers including efavirenz (without a strong CYP3A inhibitor)
600 mg twice a day
PIs = protease inhibitors; NRTIs = nucleoside reverse transcriptase inhibitors.
Adapted from reference 2.
Raltegravir is an oral agent and the firstagent to be approved in a new class ofantiretroviral drugs known as integraseinhibitors. Raltegravir exerts its mechanismof action by inhibiting the insertionof HIV DNA into human DNA by the integraseenzyme.3 By inhibiting integrasefrom performing this essential function,it limits the ability of the virus to replicateand infect new cells.3 While otheravailable agents inhibit 2 other enzymescritical to the HIV replication process—protease and reverse transcriptase—raltegravir is the only drug approved thatinhibits the integrase enzyme.3
It is indicated for use in combinationwith other antiretroviral agents for thetreatment of HIV-1 infection in treatment-experienced adults who have evidence of viral replicationand HIV-1 strains resistant to multiple antiretroviral agents.Raltegravir is available as 400-mg tablets and is to be administeredas 400 mg twice a day without regard to food. Becausethe safety and efficacy of raltegravir have not been determined,its use is not recommended in treatment-na?ve adult patients orpediatric patients younger than 16 years of age.3 The most commonadverse effects reported include nausea, headache, diarrhea,and pyrexia. The plasma concentration of raltegravir maybe decreased when given in conjunction with strong inducers ofuridine diphosphate glucuronosyltransferase such as rifampin.Raltegravir is classified by the FDA as a pregnancy categoryC drug. Pharmacists should remind patients that if a dose ismissed, it should be taken as soon as possible. If patientsdo not remember until the time for the next dose, however,patients should be instructed to skip the missed dose andresume the regular schedule. Patients should be reminded tonever take 2 tablets at the same time.
Etravirine is an NNRTI of HIV-1 and the first tobe approved in over a decade. Etravirine isthe first NNRTI to show antiviral activity intreatment-experienced adult patients withHIV resistant to an NNRTI and other antiretroviralagents.4
Etravirine is indicatedfor use incombinationwith other antiretroviralagents and is specificallyindicatedfor the treatmentof HIV-1 infectionin treatment-experiencedadult patients whohave evidence of viral replicationand HIV-1strains resistant to an NNRTI and other antiretroviralagents.4 It exerts its mechanism ofaction by binding directly to reverse transcriptaseand blocks the RNA-dependent and DNA-dependentDNA polymerase activities by causing a disruption of theenzyme's catalytic site. Etravirine does not inhibit the humanDNA polymerases α, β, and γ.4
Etravirine is available in 100-mg tablets, and the recommendedinitial dosage is 200 mg (100 mg twice a day after ameal). It is classified by the FDA as a pregnancy category Bdrug. This agent should not be coadministered with the followingantiretroviral agents: pranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, full-dose ritonavir (600 mg twicea day), protease inhibitors administered without ritonavir, andother NNRTIs.4 In addition, it should not be coadministeredwith carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine,rifabutin (when part of a regimen containing proteaseinhibitor/ritonavir), or products containing St. John's wort.4More information on potential drug interactions can be foundon the product Web site. Patients unable to swallow maydisperse the tablet in a glass of water. The most commonadverse effects associated with the use of etravirine includerash, diarrhea, nausea, fatigue, abdominal pain, peripheralneuropathy, headache, and hypertension.
Brand Name (Generic Name)
January 18, 2008
April 4, 1997
September 17, 1998
June 21, 1996
Combivir (lamivudine and zidovudine)
September 27, 1997
Gilead Sciences Inc
July 2, 2003
November 17, 1995
Epzicom (abacavir and lamivudine)
August 2, 2004
June 19, 1992
Retrovir (zidovudine, azidothymidine)
March 19, 1987
Trizivir (abacavir, zidovudine, and lamivudine)
November 14, 2000
Truvada (tenofovir disoproxil fumarate and emtricitabine)
Gilead Sciences Inc
August 2, 2004
Videx EC (enteric-coated didanosine)
October 31, 2000
Videx (didanosine, dideoxyinosine)
October 9, 1991
Viread (tenofovir disoproxil fumarate)
Gilead Sciences Inc
October 26, 2001
June 24, 1994
December 17, 1998
April 15, 1999
June 22, 2005
Merck & Co Inc
March 13, 1996
Invirase (saquinavir mesylate)
December 6, 1995
Kaletra (lopinavir and ritonavir)
September 15, 2000
Lexiva (fosamprenavir calcium)
October 20, 2003
March 1, 1996
June 23, 2006
Reyataz (atazanavir sulfate)
June 20, 2003
Viracept (nelfinavir mesylate)
March 14, 1997
March 13, 2003
August 6, 2007
Merck & Co Inc
October 12, 2007
Multiclass Combination Products
Atripla (efavirenz, emtricitabine, tenofovir disoproxil fumarate)
Bristol-Myers Squibb and Gilead Sciences
July 12, 2006
* Entry inhibitor—CCR5 coreceptor antagonist.
NNRTIs = non-nucleoside reverse transcriptase inhibitors; NRTIs = nucleoside reverse transcriptase inhibitors; PIs = protease inhibitors.
Adapted from reference 1.