Researchers launch hunt for people who control HIV without drugs

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An international appeal is underway to find people who are controlling HIV at very low viral load levels without any medication in order to learn how they control HIV, and to use this information to design potential vaccines.

The HIV Elite Controllers Consortium launched its search this week at the Sixteenth International AIDS Conference in Toronto, Canada.

The consortium is looking for two groups of people with HIV:

Glossary

elite controllers

A small subset of people living with HIV who are able to control HIV replication in the absence of antiretroviral treatment for an unusually long period of time. Definitions vary, but an elite controller is usually defined as a person whose viral load has remained below 50 copies. However, because HIV continues to replicate even in elite controllers, ART is recommended for elite controllers who have declining CD4 counts or who develop HIV-related complications. Elite controllers and viraemic controllers are members of a larger group known as HIV controllers. Around half of HIV controllers can also be described as long-term non-progressors.

long-term non-progressor

An HIV-infected person who remains free of AIDS symptoms (such as immune system decline or opportunistic diseases) for an unusually long period of time in the absence of treatment. These individuals typically have strong CD8+ T-cell responses, minimal lymph node damage and a relatively low viral load. About 10% of HIV-positive people seem to be long-term non-progressors. Most, but not all, are elite (or HIV) controllers. 

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

disease progression

The worsening of a disease.

  • so-called `elite controllers`, people who have been living with diagnosed HIV infection for at least a year and who have had a viral load below 50 copies/ml throughout that period without any treatment.
  • viral controllers: people who have been living with diagnosed HIV infection for at least a year and who have had a viral load below 2000 copies/ml throughout that period without treatment.

The study is an international collaboration between researchers in the United States, Canada, Europe and Australia, and has already identified participants from existing cohorts. But existing clinical studies of long-term non-progressors are not going to yield enough people, said Professor Bruce Walker of Harvard University Medical School at a press conference today.

“We estimate we’re going to have to find seven to eight hundred people by looking outside existing clinical cohorts,” said Prof. Walker.

Participation in the study is a very simple process: researchers need only a blood sample to be drawn by a person’s doctor, which is then sent by mail for analysis. A small number of participants will be invited to the United States for more intensive immunological studies.

Blood samples will be analysed to determine common genetic and immunologic characteristics that might have been missed in previous, smaller studies, and to examine some of the conflicting observations from previous studies of long-term non-progressors.

Research into long-term non-progression began in the early 1990s when researchers in San Francisco realised that they had patients infected between 1978 and 1980, in the very earliest phase of the epidemic, who were still healthy, with normal immune systems and very low levels of HIV in their blood.

The research, by Susan Buchbinder and colleagues caused excitement at the 1993 International AIDS Conference in Berlin, and led to the establishement of other studies around the world. It also led to an understanding that the phenomenon was more common than expected.

“If you talk to anyone who has a practice of 300 HIV patients, they will have one,” said Prof. Walker.

The median period of infection among people recruited to the study so far is 15 years, but Prof. Walker emphasised that the consortium wants to recruit people with shorter periods of infection to observe whether people who are elite controllers soon after infection experience disease progression, and if so, why.

Small studies like the Australian Blood Bank cohort, which has followed people infected in the 1980s from a blood transfusion that came from a long-term non-progressor, show that non-progressors do not have a uniform pattern of disease. Some people begin to suffer a decline in the immune system and a gradual increase in viral load eventually, and the consortium will be seeking to define the events that lead to this loss of control.

If you want to volunteer to join the study or you have patients who may be eligible you can contact the researchers directly by emailing Rachel Rosenberg at rrosenberg2@partners.org.