PK of Once Daily ART Containing Tenofovir and Atazanavir/Ritonavir

Once-daily antiretroviral therapy is being used to treat adolescents and young adults with
HIV-1 infection. When new antiretrovirals (ARVs) are developed, information on kinetics is
collected in adults, and then in children, but often the adolescent age group is
under-represented in initial or even later pharmacokinetics studies, so specific data on
appropriate drug doses to use in adolescents may be lacking; it is assumed that they should
receive the adult dose. Furthermore, as newer drugs are used in combination regimens, more
information becomes available on drug interactions that might not have been initially
anticipated. This information is usually generated in studies of adults, with little or no
specific information in children or adolescents. This is an open-label, 24-hour, single-dose
pharmacokinetic study.

Inclusion Criteria:

- Age > 18 year to < 25 years.

- Confirmed diagnosis of HIV-1 infection defined as one positive assay supported by
documentation from the subject's medical record. The result may be any of the
following:

- HIV-1 DNA PCR,

- HIV-1 RNA PCR (> 5,000 copies/ml),

- Standard ELISA with confirmatory western blot performed after 18 months of age, or

- HIV culture.

- CD4 cell count: no restrictions.

- Viral load: no restrictions.

- Current treatment with stable antiretroviral combination therapy with at least 3
active drugs for a minimum of 28 days. The treatment regimen will not be started or
changed for the purposes of participation in this study. Rather, this study will
measure kinetics of the drugs in patients who have been receiving therapy at the
direction of their treating physician.

- Regimen must be prescribed at FDA-approved doses for age.

- Regimens allowed:

- Atazanavir 300 mg po once daily plus ritonavir 100 mg po once daily, and

- Tenofovir 300 mg po once daily, plus

- At least one other antiretroviral medication prescribed at FDA-approved dose for age,
excluding other protease inhibitors and NNRTIs.

- Ability and willingness to be contacted by study personnel daily for the two days
prior to the pharmacokinetics visit, to take antiretroviral medicines at the same
time in the morning daily for at least 3 days (one of those days being the day of the
PK study visit), and ability and willingness to return to the clinic the day after
the observed administered dose for a follow-up measurement of plasma drug
concentration.

- Ability and willingness to provide written informed consent.

Exclusion Criteria:

- Pregnancy.

- Active therapy for malignancy.

- Known presence of gastrointestinal disease that would interfere with drug
administration or absorption.

- Grade 3 or higher ALT or AST.

- Grade 3 or higher Creatinine.

- Concurrent treatment with another protease inhibitor or a non-nucleoside analogue
reverse transcriptase inhibitor.

- No evidence of anemia greater than Grade 1 according to the ATN Toxicity Table for
Grading Severity of Adolescent Adverse Experiences (see Chapter 11 of ATN MOGO).