Restoring HIV-specific immunity

The immune system's ability to recognise and respond to common antigens typically improves after effective HIV therapy is started. But paradoxically, the one exception may be immune responses against HIV itself .

From the earliest stages of HIV infection, the body's cellular immune responses against the virus influence disease progression. HIV-specific immune cells are present soon after infection and play an important role in controlling HIV during primary infection and determining the viral ‘set-point’. HIV-specific CD4 T-cells orchestrate the response of CD8 T-cells, which control HIV by killing infected cells and releasing chemokines (chemical messengers) that act against the virus.

In most people who become infected, however, these HIV-specific responses are gradually lost over time. However, for reasons that are not completely understood, some individuals – known as long-term non-progressors or ‘elite controllers’ – manage to keep HIV suppressed for long periods without antiretroviral treatment.

Researchers have explored ways of stimulating the body’s natural HIV-specific immune responses, including various antiretroviral therapy strategies, therapeutic vaccines and cytokines such as interleukin-2 (IL-2).

Some studies suggest that starting antiretroviral treatment during primary HIV infection might promote persistent HIV-specific immune responses and delay immune system decline, though this approach is still the subject of controversy.¹ Anti-HIV immune responses usually do not improve during long-term antiretroviral therapy in chronically infected people – and may in fact decline – suggesting that antiretroviral drugs alone will not restore lost HIV-specific immunity.

Some experts believe that when HIV replication is suppressed to a very low level with highly active antiretroviral therapy (HAART), there are not enough viral antigens to allow for a natural immune response. Therefore, they have proposed that intermittent treatment interruption might stimulate anti-HIV immunity. Studies looking at this strategy have produced mixed results,^2,3,4 but it has become increasingly clear that treatment interruption is a potentially risky approach. For further discussion, see Structured treatment interruption.