Dr. Andy

Reflections on medicine and biology among other things

Friday, April 14, 2006

Experiment of nature

Some experiments you just have to be in the right place at the right time. Such is the case in this study in which 2 identical twins got infected with the same strain of HIV at the same time by sharing needles. They routinely shared needles with each other, but shared only once with someone else and both contracted HIV from that incident.

Because the twin brothers share the same immune system genes, including the MHC genes which are responsible for presenting peptides from infectious agents to the all-important T-cells, they should have very similar initial responses to infection.

It is known that HIV mutates rapidly, allowing it to stay one step ahead of the immune response (from commentary accompanying article):
Recent longitudinal studies of early HIV infection have shown that strain-specific neutralizing antibodies are elicited in response to the virus. When these antibodies reach a critical threshold (a matter of weeks), a resistant virus emerges. Eventually, a neutralizing antibody response to this virus develops and a new resistant virus emerges. Apparently, the virus always stays one step ahead of the evolving neutralizing antibody response.
The twin brothers, who were followed for 3 years, until one died of an overdose, had remarkably similar immune responses to the virus. And the pattern of viral mutations was similar as well, suggesting that the interacton of virus and immune system over time may be more predictable that previously thought. This might aid development of an effective vaccine.

Incredibily, a similar pair of twins were the subject of a report in the Journal of Virology published in December. This pair were infected by a single blood donor while babies. They followed a remarkably similar clinical course, developing symptoms of HIV infection at age 7, progressing to severe disease at 17 and then improving with initiation of HAART (highly active anti-retroviral therapy). By that point however, their immune responses to the virus had diverged signficantly. The cytotoxic T cells response had more differences than commonalities.

Since both sets of twins were infected by the same virus at the same time this suggests that the initial interaction of virus and immune system is predictable (as the first set of twins had very similar responses) but diverge over time, probably just by chance. This suggests any effort to target immunity based on knowledge of viral and host immune factors needs to happend soon after infection.