Reports published in the May issue of the journal Nature Medicine reaffirm the view that vaccination is the only realistic strategy against human immunodeficiency virus, HIV-1, which causes AIDS. Because HIV-1 is a disease of the immune system designed to combat diseases, strategies to fight the virus are full of paradoxes. One is the growing realization that vaccination – in other words, further challenging the immune system of a patient whose immune system is already under attack – could give it extra impetus to combat the infection.

Although the cocktail of anti-viral drugs currently offered to patients is very effective in the short term, Janet D. Siciliano of Johns Hopkins University School of Medicine, Baltimore, Maryland and colleagues show that combination therapy will never get rid of the virus completely. Instead, the virus lies low inside a small but persistent reservoir of immune-system cells. Eradicating this reservoir in any particular patient might take an average of 60 years of uninterrupted antiviral therapy, the researchers say. This is bad news, in view of the fact that the long-term use of combination antiviral therapy has unpleasant side-effects. Clearly, something else is required to eradicate the virus.

Another report, from Louis J. Picker of the University of Texas Southwestern Medical Center in Dallas, Texas and colleagues, also casts doubt on combination therapy for long-haul treatment. Combination therapy quickly clears the population of viruses to a very low level, but it also dulls the capacity of the body's ability to fight back. Immunological amnesia sets in as the memory cells of the immune system 'forget' about the viruses that still lie dormant within the body.

Vaccination – a direct challenge with virus-derived material – might help address these problems by providing a stimulus that refreshes the memory of the torpid immune system, forces the dormant viruses to come out of hiding and exposes them to direct attack. It could be that vaccination with fragments of virus, together with the administration of anti-viral drugs, could both kill viruses in the short term, and keep the immune system alert against long-term threat.

Significantly, there is no authenticated case of a person being cured of HIV-1 infection. This would be hard to establish, as viruses can survive even though there are too few to detect. There are, though, a sizeable number of people who carry the virus but remain free of symptoms. Using extremely sensitive cell assay techniques, Picker and colleagues show that such 'asymptomatic' individuals maintain an active immune response to the virus, keeping it in check – an immune response that long-term antiviral therapy tends to suppress.

This finding supports that idea that vaccination should be developed as an additional counter to HIV-1, and points up an interesting trend in research. That is, the growing realization that HIV-1, although it destroys much of the immune system, does not destroy it completely except in the final stages of the disease. Asymptomatic patients maintain a small population of cells active against the virus. At the same time, a hardened band of viruses remains in the body, despite the onslaught of antiviral therapy. The progress of HIV-1 in asymptomatic patients is a very long war of attrition in which combination antiviral therapy can play a part that helps – and hinders.