IMPAACT P1058A: Pharmacokinetic Effects of New Antiretroviral Drugs on Children, Adolescents and Young Adults

Antiretroviral (ARV) medication regimens for children, adolescents and young adults are
often prescribed based on drug resistance because of previous treatment history. In order to
find an effective regimen, clinicians must often turn to newer drugs before they have been
fully tested in adolescent or pediatric clinical trials. One of the first steps in testing
these drugs is to assess the drug pharmacokinetics (PK), or interaction between drugs and
body. This study, a follow-on protocol to the International Maternal Pediatric Adolescent
AIDS Clinical Trials Group (IMPAACT) P1058 study, will test children, adolescents and young
adults who have already been prescribed treatment regimens with new drugs. The study will
examine the PK of medication combinations featuring raltegravir, a new drug in the new ARV
class of entry inhibitors (EIs); maraviroc, a new drug in the new class of fusion inhibitors
(FIs); and etravirine, a new drug in the class of non-nucleoside reverse transcriptase
inhibitors (NNRTIs). Older medications may also be used to complete these regimens.

Participation in this study will last between 1 and 7 weeks and involve at least two clinic
visits. The first is a screening and entry visit at which a medical history will be taken
and a physical exam and blood test will be completed. The second visit will measure PK of
the medications. During this visit, participants will complete the same measures as
before—medical history, physical exam, blood test—and then be given a dose of their anti-HIV
medication regimen. After receiving the medications, participants will be monitored and give
blood samples after 1, 2, 4, 6, 8, and 12 hours. For Groups G, H, I, J, K and L an intensive
12-hour PK study will be scheduled after at least 30 days on the combination of interest.
For all Groups, the intensive 12-hour PK study should be performed within 35 days (5 weeks)
of screening/entry evaluations. Medications will not be provided through this study.

Results of the 12-hour medication monitoring tests will be delivered to participants'
physicians within 6 weeks. If, based on these results, a physician decides to change the
dosage of a participant's medication, that participant may be asked to complete a second PK
visit. Participants must have received the revised dose for at least 14 days before the PK
study can be repeated.

Inclusion Criteria:

- Certain laboratory values received within 5 weeks of the date of the screening or
entry evaluations

- HIV infected

- Stable on the specified antiretroviral (ARV) regimen for 30 days prior to screening
and entry. ARVs will not be provided through this protocol.

- Prescribed one of the regimens described in the study details by clinician on the
basis of clinical need (although the availability of drug levels may have been a
factor in clinical decision-making). The decision to initiate the regimen must have
been solely that of the prescribing physician.

- On the ARV combination of interest for at least 14 days and within 5 weeks (35 days)
of the date of screening results

- Body surface area (BSA) of at least 0.85 m2

- Participants in P1058 Version 1.0 and Version 2.0 who have switched to a regimen
specified in the entry criteria are eligible for P1058A.

- Any licensed formulation that achieves these dosages, but without including a
disallowed drug, may be used.

- Participants who have enrolled in P1058A (Groups G-L) and who subsequently switch to
a different regimen specified in the entry criteria are eligible to re-register to a
subsequent step of P1058A (re-consent required)

- Females must agree to use two reliable methods of contraception, one of which must be
a barrier method, while taking study medications and for 6 weeks after study testing

- Documentation of presence of an R5-tropic virus at the start of treatment with
maraviroc (MVC)

Exclusion Criteria:

- Pregnant or breastfeeding

- Hemoglobin level less than 8.5 g/dL

- Clinical evidence of pancreatitis as defined by moderate clinical symptoms

- Treatment with any anti-HIV or non-ARV drug that could interact with drugs under
pharmacokinetic (PK) study in the 14 days prior to study entry

- Known allergy, sensitivity, or hypersensitivity to components of two or more
study-specified drugs or their formulation