Title: Managing Antiretroviral Failure Case Discussion
1 Managing Antiretroviral FailureCase Discussion
Michael S. Saag, MDRobert Scott, MD
The International AIDS SocietyUSA
2For purposes of discussion, we will assume that
each of the following drugs are approved and
available to all for useMaravirocRaltegravirE
travirine
3Case 1
- 26 yo man diagnosed with HIV 16 months ago
- No OI
- Initial lab values
- CD4 140 cells/uL
- VL 156,000 c/mL
- Started on ZDV / 3TC (fdc) plus ATZ (unboosted)
- Never went below 50 c/mL
4Returned 4 weeks ago
- VL 123,000 CD4 155 cells/uL
- Resistance Test Ordered
- M184V
- No NNRTI mutations
- K20K/T, M36I, L63P, A71V, V77I, N88S
5In addition to an NNRTI, which nRTI drugs would
you include?
- ZDV / 3TC
- TDF / FTC
- ZDV / TDF
- D4T / 3TC
- ddI / TDF
- ABC / 3TC
- ZDV / 3TC / ABC
- Another choice
M184V
6Case 2
- 34 yo woman diagnosed with HIV 6 years ago
- Initially presented with PCP
- Initial Lab values
- CD4 82 cells/uL
- VL 106,000 c/mL
- Started on ZDV / 3TC (FDC) plus EFV
- Did well for a while, then the regimen failed
- Then treated with
- 3TC, ABC, Fos-AMP/r
- Had HSR to ABC TDF / ddI substituted
7Now on ZDV / 3TC / LPV/r
- VL 78,000 c/mL CD4 125 cells/uL
- Resistance Test Ordered
- M41L, D67N, V118I, M184V, L210W, T215Y
- No NNRTI mutations
- L10I, I13L, L33F, E34Q, M46L, I54K, L63P, A71V,
V77I, V82A
8(No Transcript)
9Would you include an NNRTI in the next regimen?
10(No Transcript)
11Which nRTI drugs would you include?
- ZDV / 3TC
- TDF / FTC
- ZDV / TDF
- D4T / 3TC
- ddI / TDF
- ddI / 3TC
- ABC / 3TC
- ZDV / 3TC / ABC
- Another choice
M41L D67N V118I M184V L210W T215Y
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13Which ritonavir-boosted PI would you include?
- LPV / r
- SQV / r
- F-AMP / r
- ATZ / r
- IND / r
- TPR / r
- DRV (TMC-114) / r
- I would not use a PI here
L10I I13L L33F E34Q M46L I54K L63P A71V V77I V82A
14Which EAP drug would you include?
- Raltegravir (MK 0518 integrase inhibitor)
- Maraviroc (CCR5 inhibitor)
- Etravirine (TMC125)
- All of the above
- I dont have enough information to decide
15 Case 3
- 42 year old man diagnosed with HIV in 1991
multiple opportunistic infections - Has taken all existing antiretroviral drugs
available except DRV and EAP drugs - Currently on TDF / FTC / TPV / r
- CD4 count 33 / uL (nadir CD4 6)
- CD4 count 3 months ago was 76 cells/uL
- HIV RNA 98,000 c/mL (max VL 167,000)
16(No Transcript)
17Would you change his ARV regimen now?
18Would you use 3TC or FTC?
19Which nRTI would you include?
- ZDV
- TDF
- D4T
- ddI
- ABC
- I wouldnt use any other nRTI agents
20(No Transcript)
21Would you use raltegravir?
22If he has R5 tropic virus, would you use
maraviroc?
23(No Transcript)
24If he has R5/X4 (D/M) tropic virus, would you use
maraviroc?
251029 Pilot Study Evaluating Safety of Maraviroc
as an Add-On to OBT in ARV-Experienced non-R5
Patients
- Selection criteria
- X4 or X4/R5 virus or indeterminate tropism
phenotype - Randomized (111), Blinded, Placebo Controlled
- ? 3 months of treatment with 3/4 classes of ARV
AND/OR resistance to at least one member of 2 of
4 classes of ARVs - At least one active drug (PI, NNRTI, or ENF) as
part of OBT - HIV RNA gt5000 c/mL
- Age 16 years
OBT 3 to 6 ARVs (note PK boosting doses of RTV
will not be counted as an ARV). 150 mg
maraviroc with PIs provides similar exposure as
300 mg without PIs.
261029 Virologic and Immunologic Outcomes Vs. OBT
at 24 Weeks - FAS, Dual/Mixed Tropic
a 4 missing values
OBT Optimized Background therapy
No differences in HIV RNA between Placebo OBT
and MVC OBT (QD or BID) were statistically
significant
Pfizer confidential For internal use only
27Which ritonavir boosted PI would you include?
- LPV / r
- SQV / r
- F-AMP / r
- ATZ / r
- IND / r
- TPR / r
- DRV (TMC-114) / r
- I would not use a PI here
L10I M36I M46L I54V Q58Q/E L63P A71V I84V L89V
L90M
28Change from Baseline in HIV RNA With GS-9137 125
mg Influence of Activity of OBT
Data from GS-9137 125 mg patients after addition
of a PI were excluded
29Would you recommend enfuvirtide?
- Yes
- No
- I am tired of all of this and am ready for HAPPY
HOUR !
30If he had used enfuvirtide in the past and
experienced treatment failure while on
enfuvirtide, would you recommend enfuvirtide?
31Case 4
- 53 yo male diagnosed with HIV in 1994
- Multiple prior regimens
- Now on Tipranavir/rit, enfuvirtide, tenofovir /
FTC (FDC) - HIV RNA lt 50 c/ml for 18 months
- CD4 265 cells/ul ( was 73 cells/ul prior to
current regimen)
32He is tired of taking this regimen and wants to
take something else. You recommend that he
- Stay the course, change wouldnt be prudent
(GHW Bush) - Goes on a Drug Holiday (STI)
- Change his regimen to a combination of newer
drugs (e.g. RTG, ETV, MVC, DRV) - Goes on a hunting trip with Dick Cheney!
33Case 5
- 32 yo woman diagnosed with HIV 4 years ago
- On first regimen ZDV / 3TC (FDC) and ATZ/rit
- HIV RNA lt 50 c/ml for 40 months
- CD4 435 cells/ul ( was 121 cells/ul prior to
starting ARV)
34She has heard of a one pill, once daily drug and
wants to change. You that she
- Stay the course, change would be Eee-vil !
(GW Bush) - Substitute TDF / FTC for ZDV /3TC
- Change her regimen to a FDC combination
TDF/FTC/EFV - Join Tony Soprano for some onion rings at a
Bayone, NJ diner !