ABC/TDF/LPV or ATV against 184/108/103/215 ?

[John2038]

Hi

What do you think of the following combos

ABC + TDF + (LPV or ATV)
or Selzentry + TDF + PI/r

against 184/108/103/215  and compared to TDF + FTC + PI/r  or  Insentress + Intelence + DRV ?

Thanks!
John

[newt]

Tenofovir + FTC or abacavir. Both FTC and abacavir do the same job here, which is promote M184V type virus, against which tenofovir is extra-effective. Personal choice would be FTC.

The other drug, boosted PI, NNRTI or another type depends on other mutations and previous treatment history, eg drugs you can't/won't tolerate.

- matt

[John2038]

Hi

1) Some physicians try to maintain the 184 because of the impact it has on the virus fitness.
What to think about this approach ?
See for eg http://www.nccc.ucsf.edu/Clinical_Resources/R_Cases.html

2) You mention that your personal choice would be to use FTC instead of ABC, that is Truvada + PI/r and not ABC + TDF + (LPV or ATV)
Why so as being given the genotype above, TDF res=2 while FTC rest=64 (standford)

3) What do you think about the potency, genetic barrier, side effect and durability of ABC + TDF + (LPV or ATV)  compared to Truvada + ATV ?

Note
Never been on meds, no others mutations

Thanks newt !

[newt]

It is the high level resistance to FTC ie M184V mutation, that makes tenofovir work much, much better better. You need to take the FTC to preserve this.

I am not sure where you get a 2 fold resistance for tenofovir because with this sequence my entry into the standford  database gives it well within normal effectiveness range, which confirms my memory's interpretation. 108 and 103 are uninteresting in this context.

Tenofovir/FTC would be a pretty standard starting point for this nuke mutation sequence especially as you have no NNRTI mutations. 

If you take the SMART/D:A:D study data into account on possible link between ABC and cardiovascular events, FTC is the smart choice (erm, no pun intended). Depends on your baseline CV risk. Plus abacavir combined with tenofovir may have unexplained interactions (therefore difficult).

PI wise, either.  On balance, Reyataz tends to have less side effects, but this is not so for everyone.

Clearly you have an options to use FTC or 3TC + a boosted PI + another drug that's not an RTI.

You also have several options which do not use RTIs at all.

- matt

[John2038]

I am not sure where you get a 2 fold resistance for tenofovir because with this sequence my entry into the standford  database gives it well within normal effectiveness range, which confirms my memory's interpretation. 108 and 103 are uninteresting in this context.

Here:

http://hivdb6.stanford.edu/asi/deployed/hiv_central.pl?program=hivdb&action=showMutationForm

with Mutation Scores checked



NRTI Resistance Mutations:   M184V, T215FIST
NNRTI Resistance Mutations:   K103N, V108IV

Nucleoside RTI

3TC....High-level resistance
ABC....Intermediate resistance
AZT....Low-level resistance
D4T....Low-level resistance
DD.....Low-level resistance
FTC....High-level resistance
TDF   Susceptible

Non-Nucleoside RTI

DLV....High-level resistance
EFV....High-level resistance
ETV....Low-level resistance
NVP....High-level resistance

Mutation Scoring

.........3TC....ABC....AZT....D4T....DDI....FTC....TDF....DLV....EFV....ETV....NVP
K103N.....................................................60.....60.....10.....70
V108IV....................................................10.....10......5.....10
M184V....60.....12.....-8.....-5.....5......60.....-8............................
T215FIST..4.....20.....35.....30.....20.....4......10............................
-----------------------------------------------------------------------------------
Total:...64.....32.....27.....25.....25.....64......2.....70.....70.....15.....80

Tenofovir/FTC would be a pretty standard starting point for this nuke mutation sequence especially as you have no NNRTI mutations. 

I have 2 NNRTI mutations: 103 108

So TDF/FTC still the best starting point ?

I'm wondering if having 2 effective drugs is better than 3 as with Isentress/Itelence/Darunavir

Their are pro/cons and I can't decide, so my question

If you take the SMART/D:A:D study data into account on possible link between ABC and cardiovascular events, FTC is the smart choice (erm, no pun intended). Depends on your baseline CV risk. Plus abacavir combined with tenofovir may have unexplained interactions (therefore difficult).

Thanks for this input.

Now ABC/TDF/PIr is also a 3 active drug regimen.
What is the best: 3 actives drugs + side effect higher or 2 active drugs + side effect lower ?

I have a normal health, so hard to decide.

PI wise, either.  On balance, Reyataz tends to have less side effects, but this is not so for everyone.

Clearly you have an options to use FTC or 3TC + a boosted PI + another drug that's not an RTI.

You also have several options which do not use RTIs at all.

- matt[/font]

Do you means that 3TC allows to preserve 184 as well ?
And any others mutations no ?

Thanks for your very interesting input.

[newt]

Yes soz being dim on the NNRTIs

Apart from Intelence they's scrubbed. Intelence is kinda complicated and it's resistance profile not completely understood. It can only be used with certain safety with boosted Prezista, boosted Invirase (yuk!), Kaletra or Isentress (plus nukes obviously). I personally would avoid all NNRTIs with your mutations.

So..for me...

Tenofovir is the starting point.

FTC and 3TC are sister drugs and interchangeable. FTC is better in terms of half-life, how long it lasts etc. Abacavir is partly effective and often combined with tenofovir in cases of resistance to good effect. All 3 will promote the M184V mutation so are choices to use with tenofovir. Personally I'd go for Tenofovir/FTC because it comes as one handy 1 x day tablet, and the practicalities and cost are important.

Isentress seems to be a highly effective drug and doesn't have any impact on lipids. But it's new so the side effect profile isn't fully known.

Prezista/r, Reyataz/r and Kaletra are all effective PIs. Reyataz uses the least Norvir (100mg v 200mg).

TDF + FTC or ABC + a boosted PI or a boosted PI + Isentress.

- matt

[John2038]

TDF + FTC or ABC + a boosted PI or a boosted PI + Isentress.
- matt

1) About boosted PI + Isentress, what could be the third drug ?
2) Assuming R5 virus only, would you add maraviroc to TDF + FTC or ABC + a boosted PI ?
3) Do you see a regimen with 3 potents drugs involving maraviroc ?

Last

Infected probably Nov 06
First genotype Dec 07       -> Mutations 108/184/215/103  subtype pr/rt = C/C (so called C)
Second genotype Aug 08  -> Mutations none subtype pr/rt = 01_AE/01_AE  (so called E)

Those two genotypes look different (expecting for 60% maybe of the others mutation).
Naive patient never on drugs
Infected by asian girl in Africa .... where resp E and C dominate..

4) What should be the most probable hypothesis :

a) co-infected C and E - so mutations archived
b) lab error
c) Mutations have disappear (dream)

Sounds to me that I'm really accumulating the bad luck with this infection if a) as being naive + single partner (gf!) + mutations + con-infection !

Tried a 3rd genotype informing a EU lab about these 2 results, but was VL = 595 in my last lab
Result pending

Finally

5) Could a phenotype be of any help, or are they tests where for eg blood sample is exposed to drugs supposed resistant, in order to see if a mutation reappear _quickly_ ?

Thanks matt!

[newt]

You have a mixed infection (as do most people). Yours is very mixed perhaps. I agree a lab error might be possible. Nonetheless, the first genotype is the most important.

A boosted PI + Isentress + Truvada is belt and braces

or

A boosted PI + Truvada may be enough

Anything else is complex (but I guess possible)

Maraviroc, don't like in this context, HIV that comes with resistance is unlikely to have a clean R5 profile.

- matt

[John2038]

A boosted PI + Isentress + Truvada is belt and braces

What about Viread only instead of Truvada, so:

Boosted PI + Isentress + Viread

will loose M184V yes ? But maybe already lost as it is a revertant mutation
Adding TDF might maintain or make it come back.

Maybe such process might explain some blips no ?

Anyway, your proposal sounds very reasonable and the best choice

Thanks matt!
Note: You might extends some life with some of your suggestions !