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TheBody.com/TheBodyPRO.com covers the 17th Conference on Retroviruses and Opportunistic Infections

The Once and Future King: What Will Replace Atripla Atop the First-Line HIV Treatment Realm?

A Blog Entry From CROI 2010

Feb. 19, 2010; 3:39 p.m. Pacific Time

Gerald Pierone Jr., M.D.

Gerald Pierone Jr., M.D.

Atripla (which is a combination of efavirenz + tenofovir + emtricitabine) is the acknowledged king in the realm of first-line antiretroviral therapy.  Le Roi est mort, vive le Roi!  Not so fast: The king still breathes. But his time is growing short.

Atripla is vulnerable primarily because of the efavirenz (Sustiva, Stocrin) component of the regimen.  Efavirenz comes with its baggage of neurocognitive side effects, teratogenicity and the exacerbation of hyperlipidemia.

The competition is shaping up in the quest to stake a claim in the coveted "preferred" position for front-line antiretroviral therapy.  So who are the contenders for the crown?

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If lineage means anything, then the heir apparent is the "quad" pill from Gilead Sciences Inc. It is an amalgamation of GS 9350 (which now has a name: cobicistat), elvitegravir (GS 9137, JTK-303), tenofovir (Viread) and emtricitabine (FTC, Emtriva).  A phase 2 study of the drug was presented at CROI, and the results were reported upon by Myles Helfand.  The quad tablet showed high levels of efficacy -- similar to the Atripla comparator -- and, as expected, had fewer central nervous system side effects.  This integrase inhibitor + boosting agent + nucleoside co-formulated tablet is poised to enter phase 3 trials in the very near future.

Despite being groomed for its role as new monarch, however, the young quad prince has some behavioral issues that have led to hushed discussions in the royal court.  The concerns center around potential nephrotoxicity, with modest creatinine increases noted in the phase 2 trials.  There is a known congenital kidney infirmity in this bloodline (from the tenofovir side of family), and the worry is that the intermarriage with GS 9350 may have exacerbated this latent tendency.  The upcoming phase 3 trials will test the mettle of this aspiring prince and determine the outcome of its planned ascendency to the throne.

Next in line for the title is the co-formulation of rilpivirine (TMC278) and Truvada (which is itself a combination of tenofovir + emtricitabine). Although no new data were presented on rilpivirine at this conference, the phase 3 results are expected to be available in several months.  Hereafter, this intermarriage of the second-generation NNRTI (non-nucleoside reverse transcriptase inhibitor) and the fixed-dose NRTI (nucleoside reverse transcriptase inhibitor) will be referred to as Newtripla (at least until the formal name is announced).  Newtripla promises to solve the most nettlesome issues associated with efavirenz by hopefully demonstrating a better lipid profile, fewer central nervous system side effects and a lack of teratogenicity.

The only murmurs emanating from the royal court regarding Newtripla have to do with potency concerns about the 25-mg rilpivirine dose and the reduction in plasma levels induced by co-administration with omeprazole (Prilosec, Zegerid). Nonetheless, Newtripla may well represent a solution to the problems clinicians and patients can experience with Atripla -- and if it does, it would also serve to cement the alliance between the realms of Gilead and Tibotec Therapeutics.

Raltegravir (Isentress) deserves mention, but it is a decided outsider in the race for the crown.  The dark-horse contender would have to overcome its greater pill burden and twice-daily dosing, but since it is already approved and gaining a following, it has some potential as a spoiler.  The royal court is feverishly awaiting once-daily data on raltegravir, but the empire of Merck & Co. Inc., not known for the swiftness of their steeds, plods forward towards Camelot with stolid intent.

The final choice is the integrase inhibitor S/GSK1349572.  This young prince, from the once-shining fiefdom of GlaxoSmithKline, has barely graduated from short pants.  Despite the immaturity of the data supporting its cause, this agent comes with impressive credentials.  Data were presented at CROI detailing the meticulous care that went into the creation of this compound. S/GSK1349572 also pledges to slay virus that eludes elvitegravir and raltegravir, and requires only once-daily unboosted dosing to be effective.

A mark against this young prince is its orphan status. With no natural allies outside of its own distant realm, it will require a long, solitary and arduous journey to even reach the kingdom.

The contest to decide the next king has been enjoined. Stay tuned for the next installment of the tale.


Copyright © 2010 Body Health Resources Corporation. All rights reserved.


 

Reader Comments:

Comment by: Jabu (Italy) Sat., Sep. 25, 2010 at 2:04 am EDT
This is all good, but I honestly think if AIDS was directly haunting the Royal family or the white house a cure would have long been found!!! SO it seems to me the idea is just to keep on introducing new medicines because the companies that produce them need to carry on carrying on. In the west everything revolves around money and nothing else. What a selfish world!
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Comment by: Whoathereboy (Boston, MA) Mon., Jul. 5, 2010 at 3:03 am EDT
Wow. This weird allusion to royalty has an oddly capitalist pig side to it's narrative, no? Makes me feel like a proletarial (word?) guinea pig.
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Comment by: florence (nairobi,kenya) Mon., Mar. 29, 2010 at 3:23 am EDT
can somebody do something about bringing down the cost of atripla in my country so that even ordinary poor kenyans who are hiv infected can also use it? i appreciate the govt, efforts to avail medications but the regimes available in the facilities have tough dosing schedules ,if atripla cost cam down am sure most people would adhere better to th etreatment regime because of the convenient one a day dosage
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Comment by: Eddie (Houston, Tx) Mon., Mar. 8, 2010 at 3:38 pm EST
Despite the creation of new potent and expensive drugs, the road to tame HIV resistance is far from over. When that happens, I believe that's where our real turning point will be, even without a cure. We'll take less drugs, not as often,with less side effects. I personally refuse that HIV have come here to stay. Maybe in the near future another virus or a super protein will emerge that would be fatal to HIV, but would be less combative and maybe harmless enough for our immune system to recognize and destroy. These new drugs will be on the market for the most part in the next coming years, but I really hope that whatever King drug that reaches the throne has his own queen as a back up to check and mate the Aids virus.
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Comment by: vincent petrosini (east brunswick, new jersey) Fri., Mar. 5, 2010 at 4:12 pm EST
Its very interesting to see the new kings emerging.and then again cash is king. Do we know if HIV treatment experienced patients will be experiencing treatment failure beyond the 3 years efficacy/ Also when do we expect to the new kings to take the court/
Let contiue to fight this devasting disease which is now considered a chronic illness. we have to continue to provide services and improved services for those in the United states of America. we are truly first and foremost. God Bless all of us as we contiue to negate the stigmus amongst eachother
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Comment by: Arinaitwe Medards (Kabwohe,Uganda) Mon., Mar. 1, 2010 at 2:10 am EST
That would be a turning point in the care of HIVers but we already have issues to do with the cost of ATRIPLA here in resource poor region with the highest prevalence of HIV, won't it be worse with these new formulations.
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Comment by: muriel silex (los angeles) Thu., Feb. 25, 2010 at 10:22 pm EST
Prince, bloodline?? Are you talking about medicines or the royal court??? heh?
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Comment by: Dr.Rakesh Bharti (Amritsar,Punjab,India) Thu., Feb. 25, 2010 at 9:02 pm EST
Is there any possibilty of Nevirapine (OD formulation)to replace efavirenz in atripla for women of reproductive age group ,poor and those having issues with CNS side effects .And also 3TC replacing FTC for economically weaker sections of society of HIVers
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Comment by: Marc (Illinois) Thu., Feb. 25, 2010 at 8:50 pm EST
Great update, thank you very much. But I am missing information about another candidate. I thought I came across an article about Tibotec working on a once daily one-pill version of boosted Prezista (Darunavir) co-formulated with Truvada? Is that just a rumor or is there any data available about that project?
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Comment by: Barry (Toledo, OH) Thu., Feb. 25, 2010 at 4:54 pm EST
The negative side effects, especially regarding issues with cardiovascular health, seem to indicate the role of Atripla are numbered. I have changed to others meds and currently feel better, but for the first time in 3 years I am able to deal with the belly fat issues Atripla seem to cause.
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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.
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