For several years there has been intense interest in why some people with HIV progress slowly to disease and have longer survival.

The proportion of people who will progress slowly to AIDS, or not progress at all, has not been established definitively. Amongst 539 men in San Francisco who had been infected with HIV for at least ten years, 8% had CD4 cell counts above 500 cells/mm³ and 31% had not developed AIDS. Furthermore, experts do not understand why some people with relatively low CD4 cell counts can remain well for long periods, or what proportion of people will stay well despite immune damage. Another American study suggested that a sizeable minority of people may fall into this category: of 579 gay men with CD4 cell counts below 200 cells/mm³, 20% did not develop AIDS within three years. A recent French study has also shown that 9% of HIV-infected patients can control HIV viral loads for up to five years in the absence of antiretroviral therapy (Madec 2004).

There are competing views regarding long-term survival. There is some evidence that a distinct group of long-term survivors does not exist. Rather, so-called 'long-term non-progressors' are the slowest progressors across a continuous spectrum. Several studies have suggested that when a group of long-term progressors is observed over time, a growing proportion start to exhibit signs of disease progression.

For example, doctors in Barcelona observed that 32 haemophiliacs at their clinic initially met a definition of long-term non-progression, as they had been infected for more than eight years and still had CD4 counts above 500 cells/mm³. However, after four years of follow-up, ten of the 32 no longer met that definition (Altisent 1996). An Australian study of long-term non-progressors found that only 54% still had CD4 cell counts above 350 cells/mm³ after five years (Guerin 2003). Similar results were seen in a recent Italian study (Vento 2004).

There is evidence though that some people do not progress at all. These patients seem able to control HIV infection, possibly due to the activity of CD8 cytotoxic T-cells or due to the genetic make-up of the body's immune system.

For example, a Swedish study of twelve slow progressors and eight long-term non-progressors identified amongst 461 HIV-positive people were tracked for between eleven and 17 years. Only one non-progressor showed an increase in viral load, and four had spontaneous decreases in HIV DNA levels. The decline in CD4 cell counts among the non-progressors was less than 15 cells/mm³ per year. In contrast, slow progressors showed a slow decline in CD4 cell counts, and an increase in viral loads in all but two cases. Analysis showed that non-progression was not due to viral defects (Brostrom 1999).

In some cases deletion in parts of HIVs genome have been found to be responsible for long-term non-progression. This has occurred in isolated groups of individuals infected with unusual strains of HIV that have parts of their nef gene missing (Deacon 1995; Kondo 2005).

Further studies are underway that are attempting to identify factors associated with long-term non-progression of HIV disease. Studies to date have failed to identify any factors that are consistently associated with non-progression (Vento 2004).

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