Re-boosting of HIV-1 Infected Subjects With Vacc-4x

Human immunodeficiency virus (HIV) infects the cluster of differentiation 4 (CD4) subset of
T-cells that are critical for initiating immune responses to infection. The level of CD4
cells in the blood is a marker of a patient's immunological status. During the course of an
HIV infection, the number of CD4 cells decreases, resulting in reduced immunological
responsiveness and ultimately immune deficiency.

Current management of an HIV infection includes antiretroviral therapy (ART). The advent of
effective ART in 1996 led to a profound decrease in type 1 HIV (HIV-1)-associated morbidity
and mortality in developed countries where ART has been available.

Despite the ability of ART to inhibit HIV-1 replication, it cannot cure infection, making
ART a lifelong treatment that requires sustained compliance and imposes significant
individual and societal financial burdens on healthcare services. Furthermore, ART side
effects (e.g., metabolic toxicity and stigmatizing body fat redistribution) often require
medication that further increases the inconveniences and financial burdens of HIV
management. Of additional concern is the emergence of viruses resistant to ART that can
result in treatment failure.

Vacc-4x is a peptide-based HIV therapeutic vaccine. The primary objective of Vacc-4x
therapeutic vaccine is to strengthen the immune system's response to HIV p24. ART
dramatically reduces the level of virus in circulation in the body, thereby allowing the
immune system to focus on the therapeutic vaccine that is administered. ART also allows for
the generation of new naïve CD4 cells that can be triggered by the therapeutic vaccine to
generate new immune responses to HIV-1. Subjects are therefore immunized with Vacc-4x in the
presence of ART to generate new HIV-specific immune responses that can sustain immunological
fitness for prolonged periods when patients are removed from ART. It is likely that periodic
boosting on ART will be required to sustain the immunotherapeutic effect - in this way ART
may become an intermittent therapy.

This study is a follow-up, re-boosting study of Study CT-BI Vacc-4x 2007/1 (EudraCT Number
2007-006302-13) performed in US and Europe (UK, Germany, Spain and Italy). All subjects to
be included have been given a therapeutic immunization with Vacc-4x during the CT-BI Vacc-4x
2007/1 study. During the study a reduction in the viral load set-point (mean viral load at
Week 48 and Week 52, or if Week 52 not reached, mean viral load of the last two measured
values before restart of ART) was seen in the Vacc-4x group compared to placebo group.
Further stimulation of the immune system by re-boosting with Vacc-4x could reduce the viral
load set-point further.

Inclusion Criteria:

1. Completed immunization regimen with Vacc-4x active and stopped ART (at Week 28) in
the CT-BI Vacc-4x 2007/1 study. (No re-start of ART is required).

2. Documented pre-study CD4 cell count ≥400x106/L.

3. Documented pre-study viral load < 300 000copies/mL.

4. Signed informed consent.

Exclusion Criteria:

1. Reported AIDS-defining illness within the previous year.

2. Malignant disease.

3. On chronic treatment with immune-suppressive therapy.

4. Unacceptable values of the hematologic and clinical chemistry parameters, as judged
by the Investigator, including creatinine values >1.5 x upper limit of normal (ULN),
and AST, ALT and alkaline phosphatase (ALP) values >2.5 x ULN.

5. Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.

6. Pregnant or breastfeeding women.

7. Women of childbearing potential not using reliable and adequate contraceptive methods
(defined as: use of oral, implanted, injectable, mechanical or barrier products for
the prevention of pregnancy; practicing abstinence; sterile) during the 5 weeks
re-boosting period including the DTH and for 2 weeks after the DTH test, or sexually
active male subjects with partners of child bearing potential unwilling to practice
effective contraception during the 5 weeks re-boosting period including the DTH and
for 12 weeks after the DTH-test.

8. Current participation in other clinical therapeutic studies.

9. Incapability of compliance to treatment protocol, in the opinion of the Investigator.