4-Day-A-Week Treatment Plan for HIV Infected Adolescents

HIV infected adolescents who require therapy face a lifetime of antiretroviral treatment.
Highly active antiretroviral therapy (HAART) is associated with short- and long-term
complications, and concerns are mounting about the cumulative effect of these complications
as adolescents enter the third and fourth decade of life. A management strategy that can
suppress the virus and decrease overall drug exposure is needed. In addition, the scheduling
requirements for antiretroviral therapies interfere with the socialization and independence
that an adolescent must accomplish to gain skills for a successful adult life. Not
surprisingly, nonadherence to prescribed medications is common in teens. This multicenter,
prospective, proof of concept trial will evaluate Short Cycle Therapy (SCT) in adolescents
with sustained viral suppression of at least 6 months. While maintenance of viral load
suppression can be viewed as either a safety or efficacy endpoint, the trial is constructed
as an assessment of safety.

Eligible participants who have been on standard HAART therapy consisting of a Protease
Inhibitor will switch to SCT therapy(4 days on treatment, 3 days off treatment each week) at
entry. Participants will be seen in the clinic every other Monday during the first month,
then monthly up to 24-weeks and then once every two months until the end of the 48-week
study period. Plasma HIV RNA levels and CD4 cell counts will be performed at every visit.
Medication adherence by self-report will be conducted every 2 weeks until week 24 and every
4-weeks thereafter until week 48. Fasting serum triglycerides and cholesterol will be
measured at baseline, at week 24 and at the end of the study.

Inclusion Criteria:

- Twelve to 24 years of age, regardless of the mode of transmission.

- Subjects must have been on a stable HAART regimen containing at least one PI and two
NRTIs and no NNRTI for at least 3 months and be willing to continue the PI-containing
regimen throughout the study period.

- Acceptable viral load defined as at least three plasma HIV-1 RNA levels ≤ 400
copies/ml within 12 months of study entry and no plasma HIV-1 RNA levels > 400
copies/ml within 6 months of entry date employing any clinically available viral load
assay.

- Pre entry plasma HIV-1 RNA level <200 copies/ml by ultra-sensitive assay (Roche 1.5)
within 30 days of study entry, performed in an assigned PACTG core virology
laboratory.

- CD4+ T cell count >350 cells/microL within 30 days of study entry.

- Ability of subject and parent or legal guardian (when appropriate) to give written
informed assent/consent and permission respectively.

- Subjects currently enrolled in ATN 015 Version 2.0 are eligible as follows:

- Subjects randomized to standard continuous therapy (control arm). These subjects
are eligible to be enrolled in ATN 015 Version 3.0 as new subjects if they meet
the entry criteria for ATN Version 3.0. If eligible, they will be followed for
the full 48 weeks.

- Subjects randomized to short cycle therapy (experimental arm). These subjects
are eligible to rollover to ATN 015 Version 3.0 and continue on SCT if they have
not met a study endpoint. These subjects may not have a viral load value that
meets a study endpoint (viz. a confirmed viral load of >400 copies/ml) and will
continue on the intensive monitoring until they have completed 24 weeks when
they will enter the less intensive 24 week phase of the study.

- Female subjects must be non-pregnant and willing to remain on effective contraception
for the duration of the study. (Examples of acceptable forms of birth control include
but are not limited to any form of hormonal contraception along with a barrier
method, double barrier method, tubal ligation, or abstinence if it is the choice of
the subject.)

Exclusion Criteria:

- On a HAART regimen containing an NNRTI or a HAART regimen with Abacavir (including
Trizivir®).

- On any prohibited medication at the time of screening. Subjects with underlying
reactive airway disease who are on either inhaled or brief, intermittent systemic
steroids can be considered but their status must be reviewed with the protocol chair
or vice chair through the standard ATN protocol query process.

- Active HIV-related opportunistic infection or any malignancy at the time of
screening. (Female subjects who have been treated adequately for cervical dysplasia
or CIN are eligible for study unless they are on systemic immunosuppressive therapy).

- Current treatment for known or suspected active serious bacterial infection.

- Pregnancy.

- Any laboratory abnormalities Grade 3 or greater as defined in Appendix III at the
time of screening.

- Subjects receiving pharmacological treatment for elevated cholesterol and
triglyceride levels.

If a candidate fails the eligibility criteria (inclusion or exclusion), she or he may be
screened again for eligibility after a period of 30 days.