A MULTI-CENTER, OPEN LABEL, EXPANDED ACCESS TRIAL OF MARAVIROC

Maraviroc is a member of a new class of antiretroviral compounds known as small
molecule CCR5 antagonists that block R5 HIV entry into CD4 cells. Maraviroc
has demonstrated selective and reversible binding to CCR5, as well as potent
antiviral activity in vitro against a wide range of laboratory adapted strains
of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in
vitro antiviral activity against clinical isolates resistant to the existing
drug classes, but has no activity against viruses that enter CD4+ cells using
CXCR4. 18 In vitro studies with approved antiretroviral medications indicate
that there is no evidence of antagonism with any members of the other four
classes of antiretroviral medications; nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase
inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors (FIs). In
vitro synergy with enfuvirtide (T-20) has been reported.

Primary Objective:
The primary objective of the maraviroc expanded access program is to facilitate
access to maraviroc for subjects, who have limited therapeutic options and to
collect safety data in a larger and more diverse patient population than that
which participated in the phase 2/3 clinical trials.
Secondary Objectives:
The secondary objective of the maraviroc expanded access program is to evaluate
the effectiveness of maraviroc in treatment-experienced patients who are
followed according to local medical practice.

This is an open label, non-comparative, international, phase 3b safety study of
maraviroc in HIV positive, treatment-experienced patients with R5 HIV who have
limited or no therapeutic options with approved therapy. It will be conducted
with approximately 600 investigators in more than 30 countries. Based on
available epidemiologic data including screening data from the A4001027 and
A4001028 studies, it is anticipated that approximately 12,000 to 18,000
treatment experienced patients will be screened for the study to identify up to
6,000 subjects with R5 HIV-1 as identified by the Monogram Biosciences (San
Francisco, California) TrofileTM assay. The tropism assay requires an HIV-1
RNA (viral load) >1000 copies/mL, and is able to detect minority X4 HIV-1 in
100% and 83% of samples when X4 HIV-1 represents >10% and >5% of the viral
population, respectively. Subjects who meet all of the inclusion criteria and
none of the exclusion criteria will receive investigator selected OBT plus
maraviroc twice daily to be initiated simultaneously. Total maraviroc dosage
in the twice daily regimen will be adjusted according to OBT and concomitant
medications (See Table 3). Ideally, subjects will be treated with at least one
additional antiretroviral agent to which their virus is susceptible and/or with
which they have not been treated. This may require that physicians and
subjects have access to more than one investigational antiretroviral agent.
Therefore, subjects receiving other investigational antiretroviral agents that
meet inclusion criteria number nine (Section 4.1 Inclusion Criteria) will be
permitted to screen for the maraviroc EAP.
Study enrollment will begin at each site following local regulatory and
institutional review board (IRB) or ethics committee (EC) approval, collection
of all required documents and site initiation. Enrollment and provision of
study drug will continue until approval and drug reimbursement is available in
the country where the subject resides or Pfizer, Inc discontinues the program.

Maraviroc therapy

To take part in this study, patients will get study drug (maraviroc) and a
number of lab tests , at no costs. The patient may or may not have a good
response to the study drug and the other drugs they receive to treat HIV
infection. The information from this study may help to treat future patients
with HIV better. There is no guarantee that every subject will benefit from
taking part in this study.