First line Treatment : New options in 2008 for which new combo ?

[John2038]

I understand that the two main types of combination actually recommended are:

2 nukes + an NNRTI
or
2 nukes + a ritonavir-boosted PI

and that the first combination usually offered (UK) usually includes:

efavirenz (an NNRTI) +
EITHER Truvada (tenofovir + FTC)
OR Kivexa (abacavir + 3TC)

I'd like to include one or more of the new option for 2008 below (assuming the are better in a way or another).


Question
What can be then the best regimen (CD4 up, VL und, TOXICITY lowest), assuming no resistances and everything else fine ?

Darunavir +truvada ?



New options in 2008
(thanks vokz for this link)

Darunavir (IP) was approved as a treatment for people with resistance. However, in a recent study, darunavir did better than Kaletra as first therapy, and future guidelines should reflect this.

Raltegravir – an integrase inhibitor – has shown similar potency to efavirenz, but has fewer side effects or interactions with other drugs. Again, this drug was first studied as a treatment for people with drug resistance, but recent studies have shown it could be as good as efavirenz in people using treatment for the first time.

NOT CONSIDERED

Atripla (efavirenz + tenofovir + FTC) – is likely to be available in Europe in 2008. It was approved in the US in July 2006. People taking efavirenz and Truvada, with an undetectable viral load for 3 months, will be able to switch to Atripla to take 1 less pill a day.

Not considered as it is not a first line treatment.

Atazanavir for first-line therapy is currently being researched, and the results are expected shortly. Although atavanavir is widely used as first line treatment, it is not approved in Europe for this purpose.

Not considered as it is not approved in Europe as first line treatment.

[Miss Philicia]

Darunavir and Raltegravir are not (yet) approved as first line treatment either.  Vokz's link kinda says this.  I'm currently on both of them and they have the least side effects of anything I've taken for 15 years, but then again I have multiple resistance issues so I am able to obtain these new meds.

I'm not sure how useful this discussion will be for you if you can't access these medications.

[John2038]

I'm not sure how useful this discussion will be for you if you can't access these medications.

They will be available in next few months.
If their benefit is much higher than the current available solutions, then I'll wait.

Normally, I can maybe wait a bit (CD4=484 VL=3k), but I'm convinced that I should start now (SMART study).

Once I can identify what seems to be the best combos, I'll carefully read their studies, and compared them with the existing one for the current solutions. Then I'll take the decision (wait or not).

[keyite]

You'll be waiting much longer than a couple of months for these drugs to become recommended for first-line therapy. Even if trials ultimately indicate that these drugs are good competitors to current recommendations there will be the very real issue of cost. I believe you reside in Europe(?) and I think you'll struggle to persuade a doctor to pay for a much more expensive drug when tried and tested, perfectly acceptable and cheaper alternatives are available.

[Miss Philicia]

They will be available in next few months.
If their benefit is much higher than the current available solutions, then I'll wait.

No dear, you don't get it.  They are available NOW, just not for first line treatments.  If and when they ARE available for first line treatments it will be years from now, not in 3 months.  These meds are non-issues for you if you are considering beginning treatment.

[John2038]

philly267

If this is confirmed:

However, in a recent study, darunavir did better than Kaletra as first therapy, and future guidelines should reflect this.

Then I tell you: my doc will prescribe it to me.

[keyite]

future guidelines should reflect this.

Yes, emphasis on future and should. Unless you're proposing to pay for them yourself then I very much doubt your doctor will oblige you in the near future - sorry.

Just come back from a talk about the costs of HIV drugs to the NHS in the UK:

Typical NNRTI-based first-line therapy is about £6-7,000 per person per year. If it's based on a PI instead then it rises to about £8-9,000 per year.

Involve 2 or 3 of the newest drugs and the cost of a combo rises to £25-35,000 per year.

Speaks for itself, I think.

[newt]

Although not approved, atazanavir/r (boosted Reyataz) is incredibly popular in London as a first-time PI, and seems to be the drug du jour to switch to if the Sustiva kicks your head into your arse. Rather than grand-daddy Kaletra, which is kinda "rough" by comparison or nevirapine.

The 96 week data on boosted atazanavir is v good, and resistance-wise it has a nice sequencing advantage. I would consider, even though not approved in Europe.  It is now a preferred PI option in the US.

As for darunavir/r (boosted Prezista), experience is limited, but the few people I know on it think it sooooo much kinder than Kaletra, apart from 1 who had a massive suedette-style rash and changed back (and back to the loperamide). If it comes to (NHS) market in the UK at a comparable price to Kaletra I expect it to be a 1st line drug in practice in 1 year for people with PI resistance, and a switch PI (by reason of side effects) for others -- at least at big London clinics.

There will undoubtedly be a Prezista non-inferiority study in the UK soon (eg Prezista + 2 nukes v standard of care), so I expect access will be possible via this route (subject to randomisation).

But most people in the UK without an interesting virus will be offered a Sustiva-based combo.  If this is not your cup of tea the phrase to secure an alternative is "I do not consent to treatment with Sustiva" << End of story.

- matt

[John2038]

keyite

Indeed. Thanks for the informations.

Now:


Source

Health first.
So I'll discuss with my doc and if confirmed, see with my insurance for the following combo (I might then pay part of the darunavir costs):

truvada + duranavir

[Miss Philicia]

. If it comes to (NHS) market in the UK at a comparable price to Kaletra I expect it to be a 1st line drug in practice in 1 year for people with PI resistance, and a switch PI (by reason of side effects) for others -- at least at big London clinics.

Matt, can you clarify what you're writing here?  Generally when I hear/read the term "1st line treatment" it's for patients with no previous experience on HAART (and which is what his thread's author is requesting as recommendations).  You're merely stating what is already the case with Prezista/Darunavir right now in the US, namely if you have resistance issues with PI's you can be prescribed this med. 

[John2038]

newt

Thanks ! You are a great source of information.
I will try to decode what you are saying about the drugs du jour in the UK.
But you have give some directions.

So re- thanks !

[newt]

John, drugs du jour..HIV prescribing is to some degree a question of trends, i hesitate to say fashion, and there is a definite trend (in London at least) for Reyataz to be the 1st PI on the prescription pad, it is in some sense the PI of the day so to speak...

Philly, I think it unlikey many people will get Prezista as 1st line treatment in the UK except for reasons of resistance -- or perhaps side effects -- at present, hence my comments. It is only approved here for people with resistance, and this is not so common now when starting treatment. The new UK treatment guidelines are being drafted as I type (well, roughly as I type) and it will be interesting to see what they say about this drug-as-1st-line given the recent strong study results.  Cost will be an issue in terms of getting to pole position.

- matt

[Cliff]

Is the cost of a drug paid for by the NHS, (negotiated rates), public information? 

[keyite]

As far as I understand it there isn't a single negotiated rate for a drug covering the whole of the NHS. The figures I quoted were for the London HIV Consortium, which covers the trusts in the capital. Prices could well vary in the rest of Britain. I doubt the precise rates are a matter of public record as that would generally put pharmaceuticals in a much worse negotiating position.

[trellium]

Health first.
So I'll discuss with my doc and if confirmed, see with my insurance for the following combo (I might then pay part of the darunavir costs):

truvada + duranavir

The current Prezista available (and approved) is 300mg per tablet. 

The table is from the POWER studies with treatment-experienced patients taking darunavir-ritonavir 600/100mg twice daily (approved dosing for treatment-experienced patients).

The ARTEMIS trial (phase 3) for treatment-naive patients is using experimental darunavir-ritonavir dosage at 800/100mg once daily.

I doubt any doctor or insurance company will approve or accept the unnecessary risks involved for treatment-naive patients w/o resistance issues wanting to start on Prezista until FDA approves the correct dosage. 

[StrongGuy]

I was just doing my periodic read over at The Body and saw this question/answer and made me think of this thread. Pretty much confirms some of the thoughts in this thread and what my personal understanding was for prescribing some of the newer drugs in the US.

http://www.thebody.com/Forums/AIDS/Meds/Current/Q188913.html

New drugs for treatment naive
Nov 27, 2007

Question

I'm confused about what doctors can prescribe for treatment naive patients.

I thought drugs like Isentress and Prezista can be prescribed to treatment naive if the patient and doctor decide it's best. but I keep hearing conflicting information. Don't doctor's have a lot of wiggle room to decide "off-label" even with HIV drugs that were approved for salvage?

Response from Dr. Young

Thanks for your post.

The new HIV medications raltegravir (Isentress) and darunavir (Prezista) are very promising; certainly for use in treatment experienced, drug resistant patients. It is indeed because of initial clinical trials data that the two medications received FDA approval for this patient population (the "on-label" indication).

Recent studies with both medications support the notion of using both in first-line therapy- showing aspects of superiority to currently recommended first-line drugs. For example, in therapy naive persons, both drugs (in combination) appear to be as- or more potent that currently recommended medications with improvement in short-term side effect profiles.

FDA approval does not restrict healthcare providers from using the drug in other settings (such as first-line patients), but rather rightly places restrictions on the ability of drug companies to promote such use until scientific studies and agency review support this use.

I'm exciting that new drugs may actually change (read: improve) current treatment options and guidelines. This conclusion is based on a very limited number of patients in just two clinical studies. On the other hand, we have years and years of successful patient experience with our current regimens- I'd need a pretty high burden of proof before discarding wholesale what we currently use.

I hope this helps, BY

The doc makes a good point. New drugs may have limited sides in the short-term, but the older drugs have more long-term data and I, personally, am more comfortable sticking with my regimen that have been around longer (and I tolerate well) than making a switch based on limited data. Hopefully the long-term data on these new drugs will be just as good as the short-term results but the proof will be in the pudding. Good food for thought overall though.

[Miss Philicia]

My issue on this topic was never whether or not a doctor COULD (legally) prescribe them, but more "would"... and even more importantly whether or not an insurer would authorize them with no record of previous HIV medications.  Certainly no ADAP program would, I would assume.

As far as the point StrongGuy makes, I do see his point and generally that's the route of thinking I would take if I was not already multiply resistant.  Why make yourself a guinea pig when you don't need to (I'm already very used to being one).  Still, on a personal level my sense, based on having zero side effects from these meds even during the first week, is that these worries are MOST LIKELY unwarranted.  I also totally think they will be first line options in the next two years, so why rush?

This is not the 90's folks, and for the majority of treatment naive patients the available first line choices will not have side effects, or very little and only lasting a couple of weeks.  Save your options for the future.

[John2038]

Hi,

The more I read about first-line treatment, the more I'm confuse about what is the best one available today.

For e.g, I was considering taking Atripla but it is not approved in EU:
Reason: One issue is likely to be the currently conflicting food recommendations for tenofovir.
In the US, Atripla is recommended to be taken on an empty stomach and tenofovir is recommended to be taken without regard to food.
Source:  http://www.i-base.info/htb/v8/htb8-10/atripla.html

I was considering Sustiva, and now Rilpivirine seems a better option for first-timers:
Reason: people taking rilpivirine were much less likely to experience the majority of side effects that are common with Sustiva, including rash, dizziness and abnormal dreams.
Source: http://www.actions-traitements.org/spip.php?breve3900

I was considering new treatments options (Isentress, Darunavir), but seems to be too early.
Reason: not enough studies.
Source: http://www.thebody.com/Forums/AIDS/Meds/Current/Q188913.html (thanks StrongGuy)

My feeling is that whatever I choose, I will always found another study offering a better alternative.
I still have also no idea on what is better :  2 nukes + an NNRTI or 2 nukes + a ritonavir-boosted PI .. (*)


I will see my doctor next Friday, and I'm still unable to come with a preferred treatment.


So may I please ask you:

What is at the end the best combos for first-timers with no resistance ?

Could you please just give me the name of your favorite combo (the one you prefer), I will read about to make a choice.

Best meaning of course (preference order if should be given to choose a treatment) :

 * CD4 increase and undetectable VL
 * long term medication (before resistance occurs)
 * Minimal toxicity
 * less sides effects as possible
 * No AZT, no lipodystrophy

Thank you for your understanding and your advices.

(*) NOTE

Low CD4 cell count, big drop in viral load, and boosted PI are risk factors for IRIS:
the investigators did find the following factors were independently associated with the development of an IRIS:

* Taking an antiretroviral regimen that included a ritonavir-boosted protease inhibitor (odds ratio [OR] = 7.41; 95% confidence interval [CI]: 1.76 – 31.29, p= 0.006) or a boosted protease inhibitor with an NNRT (p = 0.02). An NNRTI-based regimen was not associated with a significant risk of an IRIS (p = 0.06).

* A nadir CD4 cell count below 100 cells/mm3 (OR = 5.97; 95% CI: 2.33 – 15.31, p < 0.001).

* A viral load drop of 2.5 log10 or greater after starting anti-HIV treatment (OR = 2.43; 95% CI: 1.00 – 5.96, p < 0.05).

Source: http://www.aidsmap.com/en/news/5E6870A0-32EF-4583-B5B3-DB7D2E5B1B25.asp

To avoid PI then ?

[Miss Philicia]

John, Atripla was approved last month for the EU

http://www.i-base.info/htb/v8/htb8-10/atripla.html