Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

This is a double masked randomized placebo-controlled trial to examine if once daily
probiotic therapy will lower serum lipopolysaccharide (LPS) levels and immune activation
among HIV-infected youth. The study will enroll two cohorts: (1) a cohort of subjects who
are not receiving antiretroviral therapy (ART) and have absolute CD4 T-cell count greater
than 350 cells/ul and quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml;
and (2) a cohort of subjects who are receiving ART and have absolute CD4 T-cell count
greater than 350 cells/ul and and quantitative HIV-1 plasma RNA (viral load) less than 400
copies/ml.

Inclusion Criteria:

To be considered eligible for enrollment, an individual must meet the criteria listed
below.

- Age 13 years and 0 days to 24 years and 364 days at the time of consent

- Confirmed or suspected to have acquired HIV infection at age 10 years or older

- HIV-1 infection as documented by any FDA-approved ELISA test kit and confirmed by
Western blot, HIV-1 culture, HIV-1 antigen, HIV-1 DNA, plasma HIV-1 RNA, or a second
antibody test by a method other than ELISA at any time prior to pre-entry

- Absolute CD4 T-cell count greater than 350 cells/ul at pre-entry

- Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to
pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml on
two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and
including pre-entry

- Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior
to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml on
two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and
including pre-entry

- Willingness to refrain from regular use of foods/supplements containing probiotics
other than that supplied by the study during the course of study participation

Exclusion Criteria:

To be considered eligible for enrollment, an individual must not meet any of the criteria
listed below.

- Known hypersensitivity to probiotics

- Active AIDS-defining condition or acute serious illness

- Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to
pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than
50,000 copies/ml during the 24 weeks prior or at pre-entry.

- Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior
to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than
400 copies/ml during the 24 weeks prior or at pre-entry

- Known history of inflammatory bowel disease or similar disorder of the GI tract

- Current treatment with immune-modulating or immune-suppressive therapy

- Active malignancy at pre-entry

- Pregnancy

- Grade 3 or higher clinical or laboratory toxicities at the time of randomization

- Regular use of foods or supplements containing probiotics within the 2 weeks prior to
randomization (see Appendix V)

- Concurrent participation in the ATN 061, 071, 081, and/or 101 protocols