HIV-1 Tropism Arevir workshop Martin Obermeier Specialist for - - PowerPoint PPT Presentation

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HIV-1 Tropism Arevir workshop Martin Obermeier Specialist for - - PowerPoint PPT Presentation

Mar 01, 2023 19 likes •281 views

HIV-1 Tropism Arevir workshop Martin Obermeier Specialist for laboratory medicine Associate Medical center for infectious diseases Berlin Germany M. Obermeier 5/2013 Targets for HIV drug therapy plasma RNA proviral DNA Adapted

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  • M. Obermeier 5/2013

HIV-1 Tropism – Arevir workshop

Martin Obermeier Specialist for laboratory medicine Associate Medical center for infectious diseases Berlin – Germany

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  • M. Obermeier 5/2013

Targets for HIV drug therapy

plasma RNA proviral DNA

Adapted from http://www.nature.com/embor/journal/v4/n6s/fig_tab/embor857_f2.html

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  • M. Obermeier 5/2013

6558 TGGGATCAAAGCCTAAAGCCATGTG

GGGTTCTTRGGAGCAGCAGGAAGCACT 7785

6957 GTACAATGTACACATGGAAT

TAATTGTGGAGGGGAATTTT 7371

V3

Genotypic approach for coreceptor-detection

http://www.hiv.lanl.gov/content/hiv-db/MAP/landmark.html

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  • M. Obermeier 5/2013

Geno2pheno[coreceptor]

Specificity = 1 - FPR

Probability with which a CCR5-tropic virus is falsely classified as CXCR4-tropic

www.geno2pheno.org

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  • M. Obermeier 5/2013

Patient 60301

 50 yo male  HIV diagnosis 07/1995  Treatment history  7/95 - 1/96: AZT + 3TC  1/96 - 7/96: AZT + 3TC + SQV-hgc  7/96 - 9/96: AZT + 3TC + IDV  9/96 - 8/97: d4T + ddI + IDV  8/97 - 10/97: d4T + ddC + IDV  10/97 - 2/98: d4T + ddC + SQV-sgc + RTV  2/98 - 1/00: d4T + ddC + SQV-sgc + RTV + NVP  1/00 - 7/00: CBV + ABC + APV  7/00 – 9/03: TZV + APV + RTV  9/03 – 12/05: d4T + TDF + LPV/RTV  12/05 – 10/07: ABC/3TC/AZT + TDF + TPV +RTV

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  • M. Obermeier 5/2013

Patient 60301

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  • M. Obermeier 5/2013

Patient 60301

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  • M. Obermeier 5/2013

Patient 60301

Protease: L10V, K20V, L33V, M36I, M46I, G48V, I54S, A71I, V82AT, I84V

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  • M. Obermeier 5/2013

Patient 60301

3TC + DRV/ r Genotype: CCR5

3TC + DRV/ r + MVC

phenotype: D/M

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  • M. Obermeier 5/2013

Patient 60301

genotype: CCR5 phenotype: D/ M 3TC + DRV/ r 3TC + DRV/ r + MVC

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  • M. Obermeier 5/2013

“True” distribution

R5 X4

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  • M. Obermeier 5/2013

Distribution predicted with method A

R5 X4 X4-prediction method A

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  • M. Obermeier 5/2013

Distribution predicted with method B

R5 X4 X4-prediction method B

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  • M. Obermeier 5/2013
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  • M. Obermeier 5/2013

Patient 153

 38 years old, male  HIV diagnosis 1986, Risk MSM  Begin of first ART: 1998  ART-experience: 3TC, ABC, d4T,

TDF, FTC, NVP, EFV, SQV, Lopinavir, Ritonavir (fulldose and booster), Darunavir

 Last cART: TDF/FTC + NVP

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  • M. Obermeier 5/2013

Patient 153

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  • M. Obermeier 5/2013

Patient 153

 No tropism testing from viral RNA

possible

 Tropism testing from proviral DNA:

CCR5-tropic (FPR 31%)

 Genotypic Resistance: No drug

resistance associated mutations

 Switch to MVC + RAL

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  • M. Obermeier 5/2013

Patient 153

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  • M. Obermeier 5/2013

Patient 153

 Integrase-gene: N155H  CXCR4-Tropism detected from viral

RNA (FPR: 0.1%)

 But:  In overall cohort 6 Patients with dual

treatment Maraviroc and Raltegravir

 4 Patients show a viral load <50

cop/ml ant week 48

MVC + RAL

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  • M. Obermeier 5/2013

ROC’n RAL

 Maraviroc plus Raltegravir dual Therapy in Aviremic

HIV infected Patients with Lipodystrophy : Results from the ROCnRAL ANRS 157 Study. Katlama et al. CROI 2013 #566

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  • M. Obermeier 5/2013

Main inclusion criteria

 type B or CRF02 HIV-1.  ≥ 18 years old  ART for at least 5 years, and stable ART for at least 6

months.

 HIV-RNA < 200 copies/mL over the last 24 months,

and < 50 copies/mL for at least 12 months. •R5 tropic virus on HIV-DNA and with CD4 nadir ≥ 100/mm3 OR R5 tropic virus on HIV-DNA (FPR >20%) and HIV-RNA

  • f the last detectable viral load, irrespective of CD4

load.

 Clinical lipohypertrophy and defined by increased

volume of the abdominal and/or thoracic and/or cervical area (buffalo hump).

 Naïve for raltegravir and maraviroc.

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  • M. Obermeier 5/2013

Study Flow chart

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  • M. Obermeier 5/2013

Discontinuation of study due to recommendation of DMSB

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  • M. Obermeier 5/2013
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  • M. Obermeier 5/2013

What do you think?

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  • M. Obermeier 5/2013

What I think:

 We need to collect more data

http://www.eucohiv.org/