Next Generation Deep Sequencing to Evaluate Viral Tropism in HIV-1 Patients Exposed to Maraviroc Add-On Therapy

for 8 Days

*Rachel A. McGovern, Art F.Y. Poon, Manuel Leal, Miguel Genebat, Ezequiel Ruiz-Mateos, P. Richard Harrigan

Poster #TUPDA0102

Background

• The Maraviroc Clinical Test (MCT) evaluates virological response following 8 days of exposure to MVC add-on therapy

• 27 MCT patients were followed longitudinally by 454 sequence analysis

• Sequences were interpreted by Geno2Phenocoreceptor algorithm (3.5 FPR cutoff); >2% X4 virus was considered non-R5

• Analyses were conducted to identify any association between the degree of viral suppression and g2p score

R5 X4Maraviroc

X

In those screened non-R5 by genotype MVC inhibited R5 virus, however the overall pVL remained fairly constant as non-R5 virus took over the population within 8 days.

B) Screened non-R5 by deep sequencingA) Screened R5 by deep sequencing

Maraviroc exposure in patients with non-R5 virus led to strong selection for virus with an extremely low FPR

In Summary patients with non-R5 virus, when exposed to short-term maraviroc add-on therapy, demonstrated a strong selection for X4 variants having extremely low g2P scores (0 ≤ FPR < 2) in as few as 8 days.

False Positive Rate Re

lativ

e Fi

tnes

s in

the

Pre

senc

e of

Mar

aviro

c

0.

0

0.2

0.

4 0

.6

0.8

1

.0

0 5 10 15 20

B)Screened non-R5 (3.4% X4)A)