There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study he is presenting at CROI 2008. The interview was conducted by Gerald Pierone, M.D., an HIV clinician/researcher and the founder and executive director of the AIDS Research and Treatment Center of the Treasure Coast in Fort Pierce, Fla.

Shiv Gandhi

Hi, my name is Shiv Gandhi. I'm a master's degree student at the Johns Hopkins University and I am presenting a poster entitled, "The Role of APOBEC3G/F-Mediated Hypermutation in the Control of HIV-1 in Elite Suppressors."¹

Can you tell us a little bit about your study?

We were examining the clinical history of infection in elite suppressors [long-term HIV nonprogressors who are able to maintain an undetectable viral load despite never receiving antiretroviral treatment] to see whether this protein, APOBEC3G, was more active in the clinical history. APOBEC3G is a mutator. It mutates the incoming virus into the cell. Some people had thought that in elite suppressors of HIV -- patients who are able to control their virus using host defense mechanisms -- APOBEC3G may be one of those mechanisms by which they control the virus.

We were looking for signature mutations that APOBEC3G induces. We were looking at the virus that's integrated into cells. By looking at that virus, we could tell which mutations were caused by APOBEC, and we could tell how active it had been in the clinical history of infection.

We found that overall, elite suppressors don't have more active APOBEC-mediated hypermutation, contrary to some other studies that suggested APOBEC3G may be involved.² In one of our elite suppressors, however, we did find a great number of hypermutated sequences -- a great number of hypermutated viruses that was caused by APOBEC3G. Eighty percent of all viruses incoming into the cell were mutated by this mechanism, by APOBEC3G. That suggested to us that, at least in this one patient, APOBEC might be the way they control their virus replication.

How many patients did you look at in your study?

We looked at 17 patients in total: eight elite suppressors and nine HAART-treated patients.

Of the elite suppressors, one out of the eight did have hypermutation in APOBEC?

Right, a significant level of hypermutation. We detected some hypermutation in all, but only one had a significant level of hypermutation.

Are you going to be doing further studies?

We are, because we don't know if this is an effect of another mechanism or if this is a cause. What we aim to do is to look mechanistically at this protein in this one patient to see whether this protein is more active. We're looking at doing functional studies so we can see a cause rather than just a correlation.

It sounds like the take-home message, at least in your population of elite controllers, is that APOBEC hypermutation does not appear to be the dominant mode of resistance to viral progression.

Right. That's exactly the take-home message. CTL [cytotoxic T lymphocyte] responses are probably involved in most of these patients, but if we can find the mechanism by which APOBEC controls [HIV] in this one patient, it might be applicable to other patients as well.

OK, very good. Thank you.

Footnotes

1. Gandhi S, Siliciano J, Bailey J, Siliciano R, and Blankson J. The role of APOBEC3G/F-mediated hypermutation in the control of HIV-1 in elite suppressors. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 354.
   View poster: Download PDF
2. Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation. AIDS Res Hum Retroviruses. June 2005;21(6):565-574.