This is a 48-week study to evaluate the safety, tolerability, pharmacokinetics, and
antiviral activity of an investigational regimen including FDA approved HIV drugs in
HIV-infected pediatric subjects, ages 4 weeks to < 2 years old.
A 48 week, Phase II, open-label, 2-cohort, multicenter study to evaluate the
pharmacokinetics, safety, tolerability and antiviral activity of GW433908 and GW433908/RTV
when administered to HIV-1 infected protease inhibitor (PI) naive and PI-experienced
pediatric subjects aged 4 weeks to <2 years.
- Male or female 4 weeks to <2 years of age. Cohort 1 (6 months - <2 years): Subjects
must be <2 years of age at the Week 2 visit therefore the maximum age at screening is
Cohort 2 (4 weeks - <6 months): Subjects must be <6 months of age at the Week 2 visit,
therefore the maximum age at screening is 4 months for entry into this cohort.
- Parent or legal guardian is willing and able to provide written informed consent for
the subject to participate in the trial.
- Screening plasma HIV-1 RNA level >=400copies/mL.
- Subjects who, in the investigator's opinion, and following viral resistance testing
if conducted, are able to construct an active Nucleoside Reverse Transcriptase
Inhibitor (NRTI) backbone regimen consisting of 2 NRTIs.
- Subjects must meet one of the following criteria:
Therapy-naïve or PI-naïve subjects (defined as having received less than one week of any
PI-experienced subjects defined as having prior experience with no more than three PIs.
Prior RTV-boosted PI therapy will be considered as only one PI as long as the RTV dose was
lower than that recommended for use of RTV as an antiretroviral agent.
- Prior history of having received APV.
- Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) therapy within 14 days prior
to study drug administration (single or multiple dose) or anticipated need for
concurrent NNRTI therapy during the study period.
- PI therapy within 5 days prior to study drug administration (applicable only for
subjects undergoing single dose visits)
- Subjects and/or parents/legal guardians who, in the investigator's opinion, are not
able to comply with the requirements of the study.
- Subject is in the initial acute phase of a Centers for Disease Control and Prevention
(CDC) Clinical Category C event or infection (per 1994 classification) at Baseline.
Subject may be enrolled provided they are receiving treatment for the infections,
such treatment not being contraindicated with FPV, and subjects are clinically
improving at the Baseline visit.
- Presence of a malabsorption syndrome or other gastrointestinal dysfunction which
might interfere with drug absorption or render the subject unable to take oral
- Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia,
diabetes, cardiac dysfunction, hepatitis, or clinically relevant pancreatitis) which,
in the opinion of the investigator, might compromise the safety of the subject.
- Any acute laboratory abnormality at screen which, in the opinion of the investigator,
should preclude the subject's participation in the study of an investigational
compound. If subjects are found to have an acute Grade 4 laboratory abnormality at
screening, this test may be repeated once within the screening window. Any verified
Grade 4 laboratory abnormality would exclude a subject from study participation.
- Grade 3 or higher (>10x ULN) serum aminotransferase levels (alanine aminotransferase,
ALT and/or aspartate aminotransferase, AST) within 28 days prior to study drug
administration and / or clinically relevant hepatitis within the previous 6 months.
- Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days
of study drug administration or an anticipated need for such treatment within the
- Treatment with immunomodulating agents (e.g., systemic corticosteroids, interleukins,
interferons) or any agent with known anti-HIV activity (e.g., hydroxyurea or
foscarnet) within 28 days of study drug administration.
- Treatment with any of the following medications within 28 days prior to receiving
study medication or the anticipated need during the study:
Amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine,
diazepam, dihydroergotamine, encainide, ergonovine, ergotamine, estazolam, flecainide,
flurazepam, lovastatin, meperidine, methylergonovine, midazolam, pimozide, piroxicam,
propafenone, propoxyphene, quinidine, simvastatin, terfenadine, and triazolam (these drugs
have been excluded for safety reasons).
Carbamazepine, dexamethasone, phenobarbital, primidone, rifampin, St Johns Wort, (these
drugs have been excluded because they have the potential to decrease plasma protease
- Treatment with other investigational drugs/therapies within 28 days prior to
receiving study medication (note: treatments available through a Treatment IND or
other expanded-access mechanism will be evaluated on a case-by-case basis in
consultation with the sponsor).
- History of drug or other allergy which, in the opinion of the investigator,
contraindicates participation in the trial or known hypersensitivity to any study
medications (e.g. documented hypersensitivity to a nucleoside analogue).