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Interview
with Doctor Neal Nathanson —
Is Sterilizing Immunity Necessary to Prevent
HIV Disease?
Dr.
Neal Nathanson is the Director of the Office of AIDS Research,
the office responsible for setting the scientific agenda for
AIDS Research at the National Institutes of Health.
Searchlight: Given that HIV gene products like
nef and That have toxic effects in themselves, do you see
the need for some kind of adjunctive therapy for infected
individuals if you don't have sterilizing immunity from vaccines?
Nathanson:
That's sort of a sophisticated view. I guess the way I
start out is I think it's probably unrealistic to be able
to produce total sterilizing immunity. I don't know that there
are any vaccines that we have now in place that produce what
I would call sterilizing immunity. And when you think about
it, that's really a tall order because you got to set up a
sort of Maginot Line. So I guess the way I start to think
about it is whether it's a practical goal. It isn't that it
wouldn't be nice in theory to have sterilizing immunity, and
if we had a dozen examples of vaccines out there already which
produce sterilizing immunity that would give it credibility,
then I would be more enthusiastic. But I think to a certain
extent, one has to set one's sights to a realistic goal and
that's really how I came to the idea that we really need to
accept something less than sterilizing immunity.
Now
then the problem arises with HIV, of course, if you have some
degree of infection, what's going to be the ultimate outcome?
And I guess there are two ways of thinking about it. One is,
if you think about it in terms of the San Francisco cohort,
that's sort of discouraging because that suggests that all
you're going to be able to do is maybe prolong the incubation
period.
Searchlight:
What is this San Francisco cohort?
Nathanson:
The San Francisco cohort are the group of people who have
been followed from very early on in the epidemic by a group
of public health folks and epidemiologists in San Francisco.
Because they were infected early on�in the late 70's they
were the group that was followed for the longest time without
antiretroviral therapy, and therefore give the best sense
about the natural history (of HIV infection). And according
to Susan Buchbinder from the San Francisco Health Department�she's
just one of a team, she often speaks for them�there are very
few long-term nonprogressors. There were many long-term people
who were non-progressors, but most of them unfortunately have
started to have either an AIDS-defining illness, or at least
their CD4 count has slid. So one way to think about non-sterilizing
immunity is you will convert somebody from being a rapid-progressor
into being a long-term non-progressor, and that's the reason
I mention that.
The
other way of thinking about it, is that it could be more like
HIV-2, and there are in fact some people here from Africa,
who have been very active in West Africa, in Gambia, where
you have the highest concentration of HIV-2, and they have
a cohort of people there they have followed who have been
infected with HIV-2 and many of them look like they're never
going to develop AIDS. And they have correspondingly low virus
level in their blood. So, I guess the hope would be that a
vaccine that would not produce sterilizing immunity would
keep the virus sufficiently in check so that it would be more
like HIV-2, where you have this persistent infection, but
it doesn't cause disease.
Of course, there are other viruses out there that all of us
or many of us have, like herpes simplex, or E-B virus (also
known as Epstein-Barr virus), or cytomegalovirus, or varicellavirus
(chickenpox) where we're persistently infected but there is
no disease. And so it isn't totally outlandish to think that
one might have a persistent HIV infection that you live with
permanently, and . therapeutic immunization might be an adjunct
where you would keep stimulating the immune response in order
to make sure that this low-level HIV-infection was kept under
control. So I think that's a possibility.
Searchlight:
Regarding the other kinds of viruses you mentioned,
like herpes, HIV is perhaps a little different in that it
so effectively undercuts the immune responses that otherwise
could control it.
Nathanson: Right. No, that's true. So maybe the best
example would really be these HIV-2 infections where only
about 20% of those people in 10 to 15 years seem to develop
AIDS and the other 80% seem to have minimal levels of virus
and seem to be perfectly normal. That may be the best model
for what one would hope to accomplish with an AIDS vaccine
that will not produce sterilizing immunity.
Searchlight:
On another tack, given that you're the head of the Office
of AIDS Research, you have sort of a bird's eye view of all
of AIDS research. How do you feel about how the research is
developing, and our understanding of the pathology?
Nathanson: Well, if you judge by a meeting like this,
I think there are two things one would have to conclude. First
of all, there's just an enormous amount of research going
on. And secondly, at least my perspective�if you compare this
with what you heard a year ago or five years ago, is that
a lot of progress is being made in many areas. So, in the
sense of a productive research program, one has to have a
very positive view of it. The real problem is, that translating
some of these scientific advances into either effective drugs
or immune reconstitution or an effective vaccine�we're still
a ways from doing that, and partly because this is just a
very difficult virus to deal with. Not only does it infect
a lot of people, but it's also from an immunological and therapeutic
point of view a very difficult virus.
But when you think about it, this is the first virus that
we've really had any effective antiviral drugs against. I
mean, there are one or two drugs out there for herpes and
so forth, but on the whole, we have never really had good
drugs. I mean, it isn't like the bacterial infections where,
you know, you can go to the drug store and there's dozens
of antibiotics and so forth. And so, in a sense, some major
accomplishments have been done with AIDS research which really
has become the leader in the field of all virus diseases.
Because there are more drugs now available for AIDS compared
to the one or two, and for most viruses, no drugs at all.
So,
a lot has been accomplished. I think it's important to be
fairly upbeat about what has been accomplished.
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