Less than one in a hundred French HIV patients long term non-progressors

Few HIV-positive patients who are not taking HIV treatment remain free of symptoms of HIV infection in the long-term and maintain a high CD4 cell count or a very low viral load, French investigators report in an article published in the online edition of AIDS. They believe that their findings could benefit HIV vaccine research.

It has long been known that some HIV-positive individuals remain free of symptoms of HIV for many years with a CD4 cell count above 500 cells/mm³. These patients are often described as long-term non-progressors.

Slow progression of HIV disease in other patients is indicated by the maintenance of a viral low below 500 copies/ml. Such patients are described as HIV controllers. A further group of patients have an undetectable HIV viral load (below 50 copies/ml) for many years without the need for HIV treatment, and such individuals are described as elite controllers.

French investigators wished to establish how many antiretroviral-naive patients maintained a high CD4 cell count and/or a very low viral load in the long-term.

They therefore studied the French Database of HIV and identified four groups of patients:

• Individuals whose lowest ever CD4 cell count was 500 cells/mm³ in eight years of follow-up. These individuals were defined as long-term non-progressors.
• Patients whose lowest ever CD4 cell count was 600 cells/mm³ or above in ten years of follow-up, and whose CD4 cell count was stable. These individuals were categorised as elite long-term non-progressors.
• Patients who had at least 90% of viral load measurements below 500 copies/ml in ten years of follow-up. The investigators described these individuals as HIV controllers.
• Individuals who had 90% or more of viral load measurements below 500 copies/ml during ten years of follow-up and whose last viral load was below 50 copies/ml, a group of patients defined as elite HIV controllers.

Details of over 110,000 patients are recorded in the French HIV database. A total of 27,257 patients had been infected for at least eight years and had a sufficient number of laboratory investigations to be included in the investigators’ analyses. Of these, 19,390 were asymptomatic, but only 903 (5%) had never taken HIV treatment. A total of 725 of these asymptomatic, treatment-naive patients had been infected with HIV for ten or more years.

When the investigators analysed the laboratory results of these asymptomatic patients in detail they found that only 202 individuals met the definition of long-term non-progressers. These patients constituted 0.4% of all HIV-positive patients in France. Only 25 patients, 0.05% of HIV-positive patients in the country, were elite long-term non-progressors.

Their results also showed that 101 patients (0.22%) were HIV controllers, with only 69 (0.15%) being elite HIV controllers.

A total of ten patients (40%) who were elite long-term non-progressors were also HIV controllers, and of these patients, eight (32%) were elite HIV controllers.

Of the HIV controllers, 32 (46%) were long-term non-progressors and eight (12%) were elite long-term non-progressors.

“The present study, based on one of the largest existing prospective cohorts of HIV-infected patients…confirms the very low prevalence (below 0.5%) of long-term non-progressor, elite long-term non-progressor, HIV controller and elite HIV controller patients”, write the investigators.

There were some differences in the characteristics of long-term non-progressor patients and HIV controllers. Of the long-term non-progressors, 70% were men, 40% were gay men, 24% were injection drug users and 30% were heterosexuals. However, 60% of HIV controllers were men. A much lower proportion of these patients were gay men (11%), and a higher proportion (40%) were injecting drug users. Heterosexual patients constituted 30% of HIV controllers.

The investigators suggest two possible reasons why gay men were less likely to be HIV controllers than non-progressors: gay men are more likely to take HIV treatment than injecting drug users; or “the difference might also be due to a higher likelihood of superinfection among homosexual patients who continue at-risk sexual practices”.

Few patients who were elite long-term non-progressors were also elite HIV controllers. The investigators suggest that this could be because “the level of immune activation may be relatively high in elite HIV controllers with CD4 T-cell loss and low in elite long-term non-progressor patients with active viral replication”.

“Three groups of patients may hold keys to successful HIV vaccine development”, conclude the investigators, “namely viremic ‘elite’ long-term non-progressors, ‘elite’ viral controllers with CD4 cell depletion, and patients with viral control and stable CD4 cell counts.”