Re: Ritonavir Boosting

[Guest guest]

I will have my trough blood levels of Atazanavir (ATZ) measured:

1. on my existing regimen of 300 mg ATZ / 100 mg RTV;

2. on 300 mg ATZ / 50 mg RTV;

3. and if needed unboosted 400 mg ATZ

My other ARVs are FTC and tenofovir. The only other medicine I take is 20 mg Prozac. Apparently, this is enough to tax my liver. I am 5'7" and weigh 150 lbs.

I originally develoved hepatotoxicity presumably to NNRTIs in September of 2005. I need help with my liver......which will be the subject of my next post.

If one decides to take 50 mg of ritonavir from the new Kaletra tablet, are you NOT concerned about the virus becoming resistant to lopinavir?

Thank you for your insight.

VJ

That's a very good question. Why do I think boosting 400 mg Reyataz with 50 mg Norvir is sufficient when many use 300 mg Reyataz with 100 mg Norvir - and why do I think it is better to use 50 mg Norvir rather than 100 mg.

More important, is 50 mg Norvir sufficient for you?

The quick answer is likely yes, but maybe no. Have your Doctor test your Reyataz levels and find out.

Testing drug plasma levels is particularly important in your situation where your liver may not be clearing drugs adequately. You want to avoid developing excessive drug levels.

My new Doctor initially convinced me of this. I was initially taking 400 mg Reyataz with Viread and Emtriva. The higher 400 mg dose, rather than 300 mg, was chosen by my previous Doctor for two reasons. I am 6'5" and 225 which is sufficient reason, and there were already early indications that Viread decreases Reyataz levels. When my previous Doctor retired at the age of 74, we interviewed a lot of Doctors and found one we liked. On my first visit he wanted to add at least 50 mg of Norvir.

Today any Doctor can easily order a blood plasma test of Reyataz levels (and I assume other protease inhibitors as well - although that may not be the case). The first thing my new Doctor did was obtain my Reyataz level immeadiately prior to my next dose.

We know two things:

The minimum effective therapeutic blood plasma level of each protease inhibitor is published;

The blood plasma level of protease inhibitors vary widely from one person to another.

So the dose of drugs in trials is usually determined as so many mg per kg of the patients weight, or a similar formula designed to maintain adequate levels of the drug in the body. When drugs are approved the instructions are usually changed to a fixed dose. This means compromising on a higher dose which will maintain minimum therapeutic levels in everyone. While this dose is just right for a minority of people, it is excessive for most people. This is just a fact of life.

When we tested my unboosted trough Reyataz levels, they were 20% above therapeutic levels. Due to daily variation, ranging from what you eat to how your liver is doing, my Doctor convinced me that I should have a larger margin of safety than 20%. It seemed reasonable. He told me that 50 mg of Norvir was sufficent, which came in Norvir liquid, or I could take a 100 mg Norvir capsule. Having tried a taste of liquid Norvir years ago, I opted for the 100 mg Norvir capsule.

I soon felt like I had a perpetual hangover along with being nauseated and started developing diarrhea. We tested my trough Reyataz levels just before I took my next dose, and I stopped the Norvir. A few days later I was feeling great and the test results showed my trough Reyataz levels were 283% of the minimum therapeutic dose - quite excessive.

This left the option of taking 50 mg liquid Norvir. Not pleased with this idea, I suggested using one new Kaletra tablet which contains exactly 50 mg Norvir, along with some useless lopinavir. My Doctor said yes, and I felt fine adding one Kaletra tablet each day. We later obtained my trough Reyataz levels and found they were 186% of the minimum therapeutic dose of Reyataz. More than sufficient from any viewpoint.

[Guest guest]

It may also be helpful to see a small study of a combination of Reyataz with full-dose Kaletra (400 mg Lopinavir/100 mg Norvir). Not surprisingly, Reyataz levels are identical to Reyataz with 100 mg Norvir, while Lopinavir levels are 35% higher than typical Kaletra therapy. We could reasonably guess that AUC levels of Lopinavir using one tablet per day are half of 135%, or 68% of a normal Kaletra dose. I haven't measured my Lopinavir level.

Atazanavir and lopinavir/ritonavir: pharmacokinetics, safety and efficacy of a promising double-boosted protease inhibitor regimen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=AbstractPlus & list_uids=16691064 & query_hl=8 & itool=pubmed_docsum

AIDS. 2006 May 12;20(8):1131-9.

Ribera E, Azuaje C, RM, M, Feijoo M, Pou L, Crespo M, Curran A, Ocana I, Pahissa A.

Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Paseo Vall Hebron 119-129, 08035 Barcelona, Spain. eribera@...

OBJECTIVE: To assess the pharmacokinetics and tolerability of lopinavir (LPV), ritonavir (RTV) and atazanavir (ATV) as a double-boosted protease inhibitor regimen in HIV-infected adults.

METHODS:

ARM A: 16 patients who started LPV/RTV (400/100 mg b.i.d.) and ATV (300 mg q.d.) were enrolled in the study group.

LPV pharmacokinetics were compared to those of two historical groups:

ARM B: 15 patients who received LPV/RTV (400/100 mg b.i.d.); and

ARM C: 25 patients who received LPV/RTV/saquinavir (SQV) (400/100/1000 mg b.i.d.).

ARM D: ATV pharmacokinetics were compared to those of 15 consecutive patients who received ATV and RTV (300/100 mg q.d.).

Drug concentrations were measured by HPLC.

RESULTS:

LPV concentrations were significantly higher (by 35%) in arm A than in arms B and C. Median (interquartile range) LPV area under the curve (AUC)0-12 values were 115.7 (99.8-136.5), 85.2 (68.3-109.2) and 85.1 (60.6-110.1) microg/h/ml, respectively. C(max) values were 12.2 (10.7-14.5), 9.5 (6.8-13.9) and 10.0 (6.9-13.6) microg/ml, respectively. C(min) values were 9.1 (7.1-10.4), 5.6 (4.7-8.2) and 5.5 (4.2-7.5) microg/ml, respectively.

No difference was observed for ATV AUC0-24 or C(max) between arms A and D. ATV C(min) values were 1.07 (0.61-1.79) in arm A and 0.58 (0.32-0.83) in arm D (P = 0.001).

Treatment was not discontinued in any patient because of adverse effects. At 24 weeks, viral load was < 50 copies/ml in 13 of 16 patients.

CONCLUSIONS: The combination of ATV and LPV/RTV provided high plasma concentrations of both PI, which seemed to be appropriate for patients with multiple prior therapeutic failures, yielding good tolerability and substantial antiviral efficacy.

>> > Norm,> > How do you know that you need 50mg of Norvir versus 100mg? Are there any > data indicating that 400mg Atazanavir boosted with 50mg of Ritonavir is > "bio-equivalent" to the standard 300 AZV/100r?> > I'd love to reduce my ritonavir as my liver toxicity has not completely > healed yet. My ALT is still 2.6 the upper limit of normal.> > Thanks.> > VJ > > > In a message dated 10/8/2006 2:16:40

A.M. Eastern Daylight Time, > nspop2@... writes:> > While I personally take 400 mg Reyataz with a single Kaletra tablet, I do > this is for the 50 mg Norvir in the tablet, not for the small amount of > under-powered Lopinavir which accompanies the Norvir. > The advantage of this approach over a 100 mg Norvir capsule is two-fold. The > Kaltera tablet contains exactly the 50 mg Norvir I need, rather than 100 mg, > and the tablet does not contain a Castor Oil surfactant and the Norvir > casules do - which cause so much digestive upset.>