Breadth of memory CTL response against HIV associated with immune control

The number of HIV antigens recognised by memory cytotoxic T lymphocytes (CTL) is a major correlate of viral control and tends to decrease with the duration of infection, study results suggest. According to the French investigators, these findings underscore the importance of incorporating a wide range of HIV antigens into therapeutic vaccines.

For their prospective study, Dr Yves Riviere, of Institut Pasteur in Paris, and his colleagues in the IMMUNOCO Study Group enrolled 148 HIV-infected patients between 1991 and 1992, prior to the advent of highly active antiretroviral therapy (HAART).

They evaluated blood samples annually until the end of 1996 for cytotoxic responses to seven antigens. One hundred and twenty-two subjects were assessed for viral load at least once during follow-up. Over the course of the study, none of the patients received more than two antiretroviral agents.

Approximately 75% of the subjects exhibited CTL responses against one or more proteins during the trial period, the authors report in the 6 December issue of AIDS. At baseline, 23% of subjects had CTL cells that recognised none of the proteins, while 8% had cells that recognised one protein, 32% had cells that recognised two, and 17% recognised three. None of the target antigens tested on its own correlated with disease progression.

The number of recognised antigens was associated with viral load at baseline (p < 0.05) and declined at an average of 0.14 protein per year. However, the rate of reduction increased to one protein per year when opportunistic infections were present.

Dr Riviere’s group theorises that there is “a progressive exhaustion in the CTL capacity to proliferate and/or to kill specific target cells.”

The diversity of CTL response was negatively associated with CD8 cell counts, but not with CD4 counts. The authors suggest that “CD4 T-helper cell depletion does not directly influence the loss of diversity in HIV-specific CTL responses.”

In addition to the implications regarding vaccination strategies, the research team concludes that the study findings provide “new end-points for immune-based therapeutic strategies aimed at restoring a strong and protective immunity against HIV in individuals receiving HAART.”