ARV Therapy 1: Shirley

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ARV Therapy 1 Shirley

• ARV Therapy 1

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ARV Therapy 1 Shirley

• 40 year old woman
• Diagnosed HIV positive in 1995
• CD4 213 cells/mm in 2000
• Very reluctant to start ARVs
• RMP died 1999 after poor treatment experience

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ARV Therapy 1 Shirley Treatment Experience
May 2005-Oct 2005 Combivir Schering Plough CCR5
Apr 2006-Nov 2006 Kivexa Efavirenz
Nov 2006-Oct 2007 Kivexa Kaletra
Oct 2007 CD4 count 530 VL lt40 since July 2006
WT virus at baseline
Removed from study due to low level viraemia
(VL 320 at month 6) Good tolerability
Lethargy VL lt40 Adherence issues due to side
effects
CNS toxicity VL lt40 Adherence issues due to
side effects
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ARV Therapy 1 Shirley Question 1

• What would you do next?
• Continue to support the patient on same
  combination
• Undertake a tropism test?
• Undertake a resistance test?
• Supervised treatment interruption?
• Consider alternative combination?

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ARV Therapy 1 Shirley Fatigue Screen

• No physical symptoms or signs
• Normal investigations
• UE, LFT, FBC, Ca, Pi
• Iron studies, B12, folate
• Vitamin D
• TFT
• LDH

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ARV Therapy 1 Shirley Question 2

• What alternative combination would you consider?
• Switch to Truvada
• Switch Kaletra to
• atazanavir/ritonavir
• darunavir/ritonavir
• maraviroc
• raltegravir

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ARV Therapy 1 Shirley Phenotypic Tropism Testing

• Several assays available, variable concordance
• Trofile by Monogram
• Shown prospectively to reliably guide the use of
  CCR5 antagonists in patients with R5 results
• Trofile-ES (ESTA) by Monogram
• Enhanced-sensitivity - from 10 to 0.3
• Retrospective evaluation in a subset of patients
• Limitations
• Transport of sample
• Optimal sample

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ARV Therapy 1 Shirley Genotypic Tropism Testing

• Genotypic prediction methods based on V3
  sequences
• Input of clinical parameters may improve
  prediction CD4 nadir, CD8, VL

• Wetcat (Weka-tools and Tomcat)
• http//genomiac2.ucsd.edu8080/wetcat/v3.html
• WebPSSM
• http//ubik.microbiol.washington.edu/computing/ps
  sm/
• Geno2phenocoreceptor
• http//coreceptor.bioinf.mpi-inf.mpg.de/index.php

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ARV Therapy 1 Shirley Practicalities of Trofile
G2Pcoreceptor
European Drug Resistance Workshop, Stockholm 2009
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ARV Therapy 1 Shirley Stored Trofile
20
18
16
14
12
D/M-tropic
Number of patients
10
R5-tropic
8
6
4
2
0
Pre-treatment tropism
Post-treatment tropism
Waters, CROI 2009
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ARV Therapy 1 Shirley Evidence for G2P

• Berlin cohort
• 92 patients starting on MVC-containing ART
• At 12 weeks G2P and Trofile had similar PPV

Obermeier M et al. 7th EHDRW 2009. Ab 79.
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ARV Therapy 1 Shirley Case Study

• Trofile test from early CCR5 trial
• Started maraviroc October 2007 on expanded access
  program
• Continues on Kivexa and maraviroc today with
  excellent adherence, VL lt50

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ARV Therapy 1 Shirley Patient Experience
It feels like I am not taking any medication at
all!