AIDSWEEKLY Plus; Monday, May 31 & June 7, 1999
Daniel J. DeNoon, Senior Editor

The potent drug combinations keep HIV at such low levels that CD4(+) memory T cells all but disappear, a new study shows. The immune system effectively forgets how to handle the virus: a dangerous situation if drug therapy should later fail.

The findings point to the need for a vaccine that can be administered to preserve HIV specific cell-mediated immunity (CMI) during HAART.

"Early and repeated vaccination with HIV-1 determinants after initiation of HAART might be needed to retain (and potentially expand) HIV-1 specific CD4(+) and CD8(+) T cells during the period in which the main reservoirs of infectious (and antigenic) virus decrease," wrote Christine J. Pitcher of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

Pitcher et al. reported their findings in the journal Nature Medicine ("HIV-1 Specific CD4(+) T Cells Are Detectable in Most Individuals with Active HIV-1 Infection, but Decline with Prolonged Viral Suppression," Nat Med 1999 May;5(5):518-25.

The researchers measured levels of CD4(+) T-helper type 1 memory T cells specific for the HIV-1 Gag antigen. Long-term maintenance of such responses has been linked to long-term nonprogression in HIV infected individuals and in animal models of AIDS.

Most people with active, progressive HIV infection had detectable levels of these HIV specific CD4(+) T cells, with a median frequency of 0.12 percent of the memory subset (range, 0 to 0.66 percent). People with nonprogressive HIV infection had higher levels of these cells - their median frequency was 0.40 percent - but there was a high degree of overlap with the former group, as the range of nonprogressor frequency was 0.10 to 1.7 percent.

Unlike either of these two groups, people with successful virus suppression while taking HAART had very low levels of the memory CD4(+) cells. Moreover, these levels continued to decline with continued successful treatment: median frequency was 0.08 percent in those treated for 4 to 24 weeks, and only 0.03 percent in those with 47 to 112 weeks of viral suppression.

Pitcher et al. suggested that these findings could be interpreted to mean that in the absence of continued antigenic stimulation, homeostatic immunoregulatory mechanism caused the HIV specific memory cells to be replaced by memory cells with other specificities.

"Functional HIV-1 specific CD4(+) T cells are commonly available for support of anti-HIV-1 effector responses in active disease, but their decline with antiretroviral therapy indicates that immunologic participation in long-term HIV-1 control will probably require effective vaccination strategies," they concluded.

This work was supported by National Institutes of Health grants and by grants from the Texas Higher Education Coordinating Board and the University of Texas Southwestern AIDS Clinical Research Fund.

The corresponding author for this study is Christine J. Pitcher, Division of Hematopathology and Immunology, Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072.

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