Genotype. Can you please comment ?

[John2038]

Hi,

below the genotype result.

1) Could you please comment it (which combo seems the best) ?
2) All NNRTI have a High-level resistance. Does it means that the Atripla can't be taken,
   as well as the Efavirenz ?
4) Does a resistance to a PI implies a resistance to all others PI ?

Many thanks for the infos!

REVERSE TRANSCRIPTASE (RT) INHIBITOR MUTATIONS
==============================================

NRTI Resistance Mutations
M184V T215FIST

NNRTI Resistance Mutations
K103N V108IV

RT Other Mutations
T39N S48T V601 K122P D123E I135M S162C D177E G196E Q197K T200A Q207E R211K L228R


PROTEASE INHIBITOR (PI) MUTATIONS
=================================

PI Major/Minor Mutations
None

PI Minor Mutations
None

[esquimau]

figuring out the right regimens should be something you work collaboratively with your doc to figure out, make sure your doc is experienced with HIV medications and understanding of resistance profiles.

But in answer to a couple of the questions..

Yes, all the current NNRTI's are highly cross resistant so resistance to one means pretty much loosing them all.  And being resistant to Sustiva means that Atripla would be out too since its a component drug.  Effectively you'd be taking a 2-drug regimen since the Sustiva part would be ineffectual.

PI resistance profiles vary.  There's also more of them, some share resistance profiles but it generally there are more options there.  Loosing one does not mean loosing them all for the most part.

[John2038]

Based on the aidsmeds drug list (http://www.aidsmeds.com/list.shtml), seems that this mutations offers only few options.

NNRTI
None

NRTI
retrovir (AZT, ZDV), videx (ddl), viread (tdd), zerit (d4t) and eventually ziagen (abc -intermediate resistance)

But the PI mutations such as the T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddl, and to a lesser extent TDF.

So in the NRTI (excluding AZT, D4T, ABC), the remaining acceptable options are:
videx, viread, ziagen

Other option:
Isentress + Darunavir + TMC-125 e  ?

Or are there others options ?

[John2038]

Hi,

just saw a great doc.

For those with such genotype, do not loose hops:

1) First line treatment
Invirase (saquinavir, SQV)
Kaletra (Aluvia, lopinavir/ritonavir, LPV)
maybe for 6 years

2) 2n line
Isentress (raltegravir, MK-0518)
Prezista (darunavir, DRV)
Selzentry (Celsentri, maraviroc, UK-427,857)
maybe for 4 years

3) Following lines
Drugs in the pipelines, active against the K103N.

Interesting related articles:

http://www.medscape.com/viewarticle/460938
http://depts.washington.edu/hivaids/arvres/case3/discussion.html

[gerry]

The genotype does not show any PI mutations so a boosted PI will provide a good backbone in this situation, or a double-boosted PI, such Kaletra/Invirase that you mentioned below.

215F is an NRTI mutation, not a PI mutation.  It is possible that there are more NRTI mutations here that were not picked up by the genotype.  This is where the phenotype would be useful if you want to know which remaining NRTIs may be useful in this situation.  Like you mentioned, Viread may still work especially when combined with Epivir or Emtriva (to induce the M184V which would make Viread work better) but this will not be a reliable backbone.  However, it might still work when combined with a boosted PI or double boosted PI.

Using the newer agents like Isentress is also an option combined with a boosted PI.

Good luck.

[John2038]

Hi Gerry,

Jena's mutations

PIs - 63P
NNRTIs - 103N
NRTI - 67N, 70R, 118I, 184V, 215F, 219E, 219Q

My mutations

NRTI  :  M184V T215FIST
NNRTI : K103N V108IV

So we are having almost (in the exception of V108IV) the same genotype.

Are the answers you provided with newt in the Jena's thread  100% applicable here ?

The concensus in the Jena's thread was:

"Kaletra/Reyataz/Viread/Epivir (or Truvada to replace the Viread/Epivir) route, you have one expert backing you up".

While above, in this thread, your answer was:

"Like you mentioned, Viread may still work especially when combined with Epivir or Emtriva (to induce the M184V which would make Viread work better) but this will not be a reliable backbone."

And while newt advises are (http://forums.poz.com/index.php?topic=17830.0):

(1) a boosted PI + Truvada (tenofovir + FTC), or perhaps << conservative, well understood
(2) a boosted PI + Isentress + Truvada << belt + braces, new

Using tenofovir is subject to baseline kidney health -- if kidneys is a problem then:

(3) a boosted PI + Isentress + FTC/3TC alone or 2 -3 other nukes << choice will depend on doc's approach to your nuke mutations, many options here.

Now what about:

TIBOTEC Study result: 84% 48w VL<50     FOR    Darunavir (800 mg) +  Ritonavir (100 mg) + Truvada
TIBOTEC  Study result: 78% 48w VL<50    FOR    Kaletra (lopinavir/ritonavir 800 mg/200 mg) + Truvada

Thanks !

[John2038]

Joel E. Gallant, M.D., M.P.H. answer's

2 NRTIs + a boosted PI is probably a fine choice. Even though you have M184V, a combination of Truvada plus a boosted PI is probably fine, since M184V helps to increase tenofovir activity. I would use Truvada, not tenofovir + ddI. The combination of tenofovir and ddI is generally not recommended. The choice of boosted PI probably doesn't matter, at least in terms of effectiveness. You could use Kaletra or else RTV plus either atazanavir, fosamprenavir, or darunavir.


Racivir is not available. It may never be available.

It would be silly to use enfuvirtide--you have too many other choices.

There is no evidence supporting the use of dual-boosted PIs, such as Kaletra plus Invirase. I wouldn't do that.

I don't see any point in doing a Tropism assay in this case. The only other viable option other than the one I mentioned is to use raltegravir along with a boosted PI (with or without one or 2 NRTIs.)

It's currently recommended that you start therapy at CD4 counts below 350, though that doesn't mean you couldn't start earlier.

So the following combos:

1st choice
Truvada + Kaletra
Truvada + Ritonavir + Atazanavir
Truvada + Ritonavir + Fosamprenavir
Truvada + Ritonavir + Darunavir

2nd choice
Isentress + boosted PI (with or without 1 or 2 NRTIs)

Not justified (as NRTIs available)
Kaletra + Saquinavir (as have NRTIs)
Usage of enfuvirtide (Fuzeon)

Not recommended 2xNRTIs choice
tenofovir + ddI

Then (if resistance above)
Etravirine (TMC-125)
Selzentry (Celsentri, maraviroc, UK-427,857) - if CCR5 only

NEWT you was right (again )

Thanks also Gerry !
Now I'm wondering about the conclusion  (as I believe Gerry you know what you are talking about)
Viread may still work especially when combined with Epivir or Emtriva..
.. but this will not be a reliable backbone.
However, it might still work when combined with a boosted PI or double boosted PI.


Thanks also to esquimau !