amfAR, The Foundation for AIDS Research

Long-Term Survivors of HIV

By Jeffrey Laurence, M.D.


September 2007—Research into "experiments of nature"—be they naturally occurring mutations in our genes, fortuitous incidents, or unfortunate accidents—have illuminated critical pieces of the HIV/AIDS puzzle. They have led to definition of the means by which certain people fail to get infected despite frequent viral exposure, or become infected yet show little damage to their immune systems despite years or even decades of infection and no antiretroviral treatment. amfAR-funded researchers have made signal contributions to these findings and continue to do so, as illustrated by a recent paper co-authored by amfAR grantee Dale McPhee.

Writing in the July issue of Virology Journal, Dr. McPhee and colleagues studied HIV samples from an unusual group of people in Sydney, Australia. They had all become infected through blood transfusions obtained from a single donor who, at the time of these donations from 1981 through 1984, was healthy and unaware of his HIV infection. Five of these individuals had slow development of HIV disease or no disease, with normal T cell counts and low to undetectable viral loads over a decade or more, in the absence of anti-HIV therapy.

Initially, both the blood donor and the blood transfusion recipients had virus with changes in a single HIV gene, nef. These mutations hobbled nef, rendering it incapable of carrying out several functions important to HIV growth. It was postulated that this must be a key factor in limiting HIV progression, a hypothesis that served to support animal studies in which nef was removed from monkey AIDS viruses, forming an early prototype of a so-called "replication competent" HIV vaccine.

The excitement surrounding those conclusions was short-lived. Other non-progressing people, apart from the Sydney group, had virus with perfectly normal nef genes. And while the blood donor and recipients described above continued to develop very similar changes in nef, over the years they had different clinical outcomes. The Virology Journal report found that each person developed very different changes in another key determinant of HIV disease, the viral envelope gene.

What must now be explored is how those changes in the envelope gene relate to a person's ability to resist the usual progression of HIV infection to AIDS. The envelope changes were independent of how quickly HIV grew or killed T cells in a test tube. They were also independent of the specific receptor HIV used to enter a cell. Defining the means by which these changes affect the course of an HIV infection should offer insights into novel means of preventing HIV disease development in others.

Dr. Laurence is amfAR’s senior scientific consultant.