2nd National Conference Human Retroviruses and Related Infections Washington, DC - January 29 - February 2, 1995

Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 18)

Greenough T¹, Brettler D², Forsberg A², Sullivan JL^1
1University of Massachusetts Medical Center, and ²Medical Center of Central Massachusetts, Memorial Hospital, Worcester, MA 01605

Approximately five percent of most HIV-1 infected cohorts maintain normal CD4 lymphocyte counts without therapeutic intervention for extended periods of time. We have followed 7 infected individuals with hemophilia in a cohort of 144 who have maintained normal CD4 values for more than 10 years following infection and who have never received antiretroviral therapy. Studies performed have included lymphocyte surface markers, viral culture, quantitative DNA PCR, ICD P24, and virus-specific cytotoxic T lymphocyte activity. Compared with seronegative (SN) members of this cohort, these non-progressors (NP) have similar CD4 lymphocyte counts: 876/µl (NP, n=6) vs. 840/µl (SN, n=12). Recovery of virus in culture has been dramatically less successful than in the cohort with 8% positive in standard PBMC cocultures. This contrasts those with progressive disease for whom >80% of such cultures are positive. Engraftments Of PBMC in SCID mice, coculture with autologous PHA stimulated and MT-2-transformed CD4+ cell lines, and CD8-depleted PBMC cultures are among other techniques attempted for recovery of virus. ICD P24 assays have been consistently negative. Quantitative DNA PCR results typically show <10 copies per 10⁶ PBMC. Primary CTL assays have shown activity in 6/6 studied to date. Some individuals have had intermittent activity against viral antigens. These studies show that individuals with normal CD4 counts despite more than ten years of infection with HIV-1 have remarkably low viral burdens in circulation. That these individuals maintain activated circulating CTL indicates ongoing viral antigen expression.

Keywords: Animals, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Communicable Diseases, HIV-1, Hemophilia A, Infection, Mice, T-Lymphocytes, Cytotoxic, Viral Load

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1995-01-29
18

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