Host T-Cell Control of HIV

In this session Bruce Walker updated his current understanding of the ability of the immune system to control HIV infection. This update has become a regular feature of many major meetings since Dr. Walker and colleagues first published data regarding the preservation of HIV-specific immunity in patients treated with potent antiretroviral therapy during early primary infection (Rosenberg, et al., Nature 2000; 407: 523-526).

That widely cited study seemed to suggest that HIV-specific immunity could be preserved/protected when HAART was started very early after HIV infection. Treatment interruptions and then stopping HAART for a prolonged time were strategies employed to evaluate whether viremia could be controlled in this select cohort.

The first fly in the soup was reported by Dr. Walker in Barcelona when he reported the case of a study participant who became superinfected with another clade B virus yet demonstrated an impressive rebound in viremia levels suggesting that the HIV-specific immunity for his own clade B virus was not sufficient to control the new virus. Now comes more bad news for those expecting that the immune system can be easily manipulated to control HIV. As the cohort of patients described above has been followed for a longer period of time off therapy, essentially all of them have exhibited loss of control of viremia.

Dr. Walker then spent the rest of the time exploring possible mechanisms for that loss of immune control. Several examples were given where relatively modest viral mutations resulting in sequence changes were associated with loss of immune control. In his summary he stated that the challenge to develop an effective therapeutic vaccine is a major one but that understanding precisely how immune control is evaded is crucial to that effort. When asked a question from the audience he pointed out that the clinical benefit of immediate initiation of HAART for primary infection remains unproven.

My view of this data is that the probability that an effective therapeutic vaccine will be available soon is low (especially considering that it often took >450 days before viral escape occurred). A therapeutic vaccine would need to be evaluated for a very long time (years) to assess whether virologic control can be maintained. As highlighted by Dr. Walker, more effort will need to go into understanding the basic immunopathogenesis of HIV infection.