• Genetic, Virological, and Immunological Characterization of a Cohort of Long-Term Monogamous HIV-Discordant Couples (Poster 52)
  Authored by R. Braganza, S. Beddows, S. Frazeo, T. Dong, T. Rostron, S. Rowland-Jones, J. Weber, and S. Fidler
  View the original abstract

Why some people with high-risk behavior do not get infected with HIV is an ongoing mystery. If we knew the answer we would better understand how to protect HIV-uninfected individuals from getting HIV in the first place, and all of us would be out of business (because there would not be new cases of HIV).

In this study, Braganza et al. looked at discordant couples -- couples in which one of the members has HIV infection and the other member does not -- who, in spite of having unprotected sex, remain uninfected. We all have seen these kinds of couples and we all have wondered how the uninfected partner remains uninfected. Braganza went further and tried to answer the question.

The researchers looked at eight couples (six homosexual, two heterosexual). They looked at factors that can explain this phenomenon and asked three questions:

1. Is there anything in the CD4 cells of the seronegative partner making them resistant to the infection?
   We learned three years ago that deletions in the CCR5 receptor make those cells resistant to HIV infection. The variant gene occurs primarily in Caucasian individuals.

   NOTE for the non-initiated: There are two copies of each chromosome in every cell of an organism. Humans have 23 pairs. One set of chromosomes comes from the mother and one comes from the father. We have one copy of each gene in each of our chromosomes. If you have the same copy of a gene in both chromosomes we say that you are "homozygote," if your two copies of a gene are different you are "heterozygote."

   Individuals who are homozygous for the deletion in the CCR5 gene are resistant to HIV infection (something that happens in about 1% of the population). Heterozygous (about 15%-20% of the population) can become infected but appear to have a slower rate of disease progression. There are mutations in other co-receptors that also seem to affect the progression of HIV like CCR2 and SDF-1 alpha.

   However, this was not the case in these eight couples: their CD4 could be infected in vitro, and they did not have these protective mutations in their CD4 cells.

2. Was there anything wrong in the virus that made these subjects less prone to getting infected?
   There are several viruses with specific mutations that make them less pathogenic (for example viruses with deletions in the nef gene). That was not the case either. The virus present in the infected partner was able to infect the CD4 cells of the uninfected partner in vitro just fine.

3. Was there something in the immune system of these individuals that made them resistant to the infection?
   This is the most interesting part because this is the part that we might be able to interact with and modify. In this case there was some evidence, measured by ELISPOT, of CTL responses against certain epitopes of the virus of the infected partner. This suggests that some individuals are able to mount a protective immune response against HIV.

   Now we just have to figure out how to do it on a large scale.

What are the limitations of this study? The first one is the size. We need larger studies. It could be that these couples just represent the extreme corner of a bell shaped distribution, and that they were just lucky and that is why they did not become infected. We also need to know more about the behavior of these couples: were they having sex less frequently than couples who did transmit the infection? Was the sex different in any way? What was the viral load in the genital secretions?

In spite of those limitations, these kind of studies are important because if we learn what makes the immune system prevent infection, we will be in a better position to develop a preventive vaccine, which should be one of our main goals for the next decade. We cannot change our genes or our CCR5 receptors (we are what our genes say we are), and we cannot change the virus that is circulating around, but maybe in the future, with the use of vaccines, we will be able to develop the kind of immune protective responses that are needed to prevent HIV infection.