Preliminary Evaluation of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen in Children with HIV-1 Infection

Sei, Shizuko
Sandelli, Susan L.
Theofan, Georgia
Ratto-Kim, Silvia
Kumagai, Mutsuko
Loomis-Price, Lawrence D.
Cox, Josephine H.
Jarosinski, Paul
Walsek, Claire M.
Brouwers, Pim
Venzon, David J.
Xu, Jing
Pizzo, Philip A.
Moss, Ronald B.
Robb, Merlin L.
Wood, Lauren V.

¹HIV and AIDS Malignancy Branch
²Pediatric Branch
³Biostatistics and Data Management Section, National Cancer Institute
⁴Departments of Pharmacy, Clinical Center, National Institutes of Health, Bethesda
⁵Departments of Nursing, Clinical Center, National Institutes of Health, Bethesda
⁶HIV Clinical Interface Laboratory, SAIC-Frederick, National Cancer Institute—Frederick Cancer Research and Development Center, Frederick
⁷HIV Laboratory, Henry M. Jackson Foundation
⁸Department of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland
⁹The Immune Response Corporation, Carlsbad, California
¹⁰Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts

^aPresent affiliations:First Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan (M.K.); Texas Children's Cancer Center, Baylor College of Medicine, Houston (P.B.); Department of Pediatrics, Harvard Medical School, and Department of Medicine, Children's Hospital, Boston, Massachusetts (P.P.).

Reprints or correspondence:Shizuko Sei, HIV Clinical Interface Laboratory, SAIC Frederick, NCI-FCRDC, NIH, Bldg. 322, Rm. 27B, Frederick, MD 21702 ([email protected]).

Received 30 December 1998; revised 16 April 1999

Presented in part:2nd International Symposium on Pediatric AIDS, Thailand, March 1997.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, US Army or the Department of Defense, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government. The study was approved by the Institutional Review Board, National Cancer Institute, and written informed consent was obtained from the parent or legal guardian of each child.

Financial support:This work was supported, in part, by Cooperative Agreement DAMD 17-93-V-3004 between US Army Medical Research and Material Command and the Henry M. Jackson Foundation for the Advancement of Military Medicine. M.K. is a recipient of a fellowship grant supported by the Immune Response Corporation under the Clinical Trial Agreement no. 0418.

Journal of Infectious Diseases 180(3):p 626-640, September 1999. | DOI: 10.1086/314944

The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1—infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2.5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log₁₀ HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n = 4 ] vs. 2.5 U [n = 3], respectively; P = .034). Levels of regulated-on-activation, normal T cell—expressed and —secreted chemokine produced from HIV-1 immunogen—stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen—specific antibody responses (P < .02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P < .01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.