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Journal of Virology, July 2005, p. 8121-8130, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8121-8130.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Longitudinal Assessment of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon Responses during the First Year of Life in HIV-1-Infected Infants

Barbara L. Lohman,1,2* Jennifer A. Slyker,7 Barbra A. Richardson,3,5 Carey Farquhar,2,4 Jenniffer M. Mabuka,1 Christopher Crudder,1 Tao Dong,7 Elizabeth Obimbo,1 Dorothy Mbori-Ngacha,1 Julie Overbaugh,5,6 Sarah Rowland-Jones,7 and Grace John-Stewart1,2,4

Department of Paediatrics, University of Nairobi, Nairobi, Kenya,1 Departments of Epidemiology,2 Biostatisics,3 Medicine, University of Washington, Seattle, Washington,4 Divisions of Public Health Sciences,5 Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington,6 Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, England7

Received 3 December 2004/ Accepted 13 March 2005

Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-{gamma}) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21 (29%) of infants infected in utero and peripartum, respectively (P = 0.09), and in ~50% of infants thereafter. Peaks of HIV-specific spot-forming units (SFU) increased significantly with age in all infants, from 251/106 peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/106 PBMC at 12 months of age (P = 0.03), although when limited to infants who survived to 1 year, the increase in peak HIV-specific SFU was no longer significant (P = 0.18). Over the first year of life, infants with IFN-{gamma} responses at 1 month had peak plasma viral loads, rates of decline of viral load, and mortality risk similar to those of infants who lacked responses at 1 month. The strength and breadth of IFN-{gamma} responses at 1 month were not significantly associated with viral containment or mortality. These results suggest that, in contrast to HIV-1-infected adults, in whom strong cytotoxic T lymphocyte responses in primary infection are associated with reductions in viremia, HIV-1-infected neonates generate HIV-1-specific CD8+-T-cell responses early in life that are not clearly associated with improved clinical outcomes.

* Corresponding author. Mailing address: IARTP, 325 Ninth Ave., Box 359909, Seattle, WA 98104. Phone: (206) 543-4278. Fax: (206) 543-4818. E-mail: bllohman{at}iconnect.co.ke.

Journal of Virology, July 2005, p. 8121-8130, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8121-8130.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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