AIDSWEEKLY Plus, 3 June 1996
Daniel J. DeNoon, Senior Editor

Vigorous HIV specific cytotoxic lymphocyte (CTL) responses and paradoxically weak neutralizing antibody activity characterize the immune responses of long-term survivors with the lowest viral loads.

The finding has direct implications for HIV vaccine research.

Harvard University researcher Thomas Harrer and colleagues identified 10 long-term nonprogressors - with CD4 T-lymphocyte counts of >500 cells/(micro)L after at 10 years of HIV infection (range 11-15 years) - in the San Francisco City Clinic cohort. This now-famous cohort was assembled in 1978 to study hepatitis B prevalence.

Despite great heterogeneity among the 10 subjects, Harrer et al. found that the four individuals with the lowest viral loads had a similar immunologic profile.

They reported their findings in the journal AIDS Research and Human Retroviruses ("Strong Cytotoxic T Cell and Weak Neutralizing Antibody Responses in a Subset of Persons with Stable Nonprogressing HIV Type 1 Infection," AIDS Res H, 1996;12(7):585-592).

"All four subjects with the lowest viral loads on initial evaluation remained stable with CD4 counts greater than 500 cells/(micro)L during follow-up for 23-32 months, and maintained persistently low viral titers," Harrer et al. reported.

"In these individuals a relatively consistent pattern of immune responses was detected. All had detectable CTL activity, including three with in vivo activated CTL, yet all had weak to undetectable neutralizing antibodies against the panel of primary isolates."

A strong CTL response alone was not enough: one subject with strong CTL activity and a high viral titer had HIV disease progression during the observation period.

"Our finding that vigorous CTL responses can be detected in persons with low viral loads and stable nonprogressing disease supports the hypothesis that CTL may contribute to maintenance of the asymptomatic state, although these and other studies indicate that progression can occur even in the presence of vigorous CTL activity," Harrer et al. noted.

"Additional expanded studies in both progressors and nonprogressors will be required to adequately address these issues, and to determine whether augmenting the cellular or humoral immune response may confer benefit in infected persons."

This research was supported by the Bundesministerium fur Forschung und Technologie, Bonn, Germany, by the Pediatric AIDS Foundation, by National Institutes of Health Grants AI28568 and AI30194, and by a contract from the NIH (Correlates of HIV-1 Immune Protection).

The corresponding author for this study is Thomas Harrer, AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.

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