Robert Bank: Based on your research, Dr. Cohen, what role should antiretroviral therapy (ART) treatment of HIV infected people play in prevention efforts?
Dr. Cohen: Currently there are three important uses for ART: one is for post-exposure prophylaxis; we already have guidelines for use of ART in that arena. Second, there are a large number of trials going on exploring the possibility of pre-exposure prophylaxis using ART either orally or topically before exposure. The most important issue is the possibility that treatment also serves as prevention. When a person goes on treatment and the viral concentration in both the blood and genital secretions is suppressed, a person might be rendered much less contagious. We are currently trying to prove this.
Robert Bank: Where are we with respect to number three as far as clinical trials are concerned?
Dr. Cohen: That's a good question. Treatment as prevention has captured worldwide attention. The New York Times did an editorial calling treatment as prevention "a breathtaking aspiration for AIDS." Two big assumptions are currently being tested in clinical trials. One assumption is that early treatment serves to benefit the individual. We are trying to prove that the benefit of much earlier treatment actually outweighs the cost. I don't just mean the cost in dollars; I mean also unexpected toxicities as well. The second assumption being tested is, whether in fact, by using antivirals we suppress virus in genital secretions so much that a person is actually rendered less contagious to their partner. The National Institutes of Health (NIH) is sponsoring a trial that is testing both these assumptions. The trial has enrolled more than 700 couples, but it won't be done for several years.
In addition population-based studies can determine whether, if enough people in a population are treated with ART, HIV incidence in the population would go down. I think Dr. Julio Montaner is trying to organize such a trial in British Columbia. Robert Bank:What are the difficulties of such a trial?
Dr. Cohen: First, a trial to prove that ART prevents transmission requires the use of serodiscordant couples. Such couples can be difficult to enroll and manage. Second, we are obligated to use every possible counseling mechanism to prevent HIV transmission. So with really good counseling you might make transmission so improbable that you need a very large number of subjects enrolled in the trial. Third, couples don't always sustain their relationship. If they break up the trial becomes more difficult. Fourth, we anticipate early benefits from ART but we are not sure they can be sustained; for example, you might see that antiviral therapy reduced transmission dramatically in the first year or two, with benefit lost because of lack of adherence or development of resistance, or other unanticipated problems. So such a trial has to go on for a very long period of time.
The big problem with a population based trial is the challenge in treating an entire population.
Robert Bank: Is there some way that you can explain to our readers the importance of other STDs in the acquisition and transmission of HIV?
Dr. Cohen: There is a lot of confusion around this issue. At the end of the day HIV is an STD; most of the people who acquire HIV acquire it sexually.
The classical STD pathogens that cause ulcers and inflammation are transmitted, generally speaking, much more readily than HIV. Someone who is co-infected with HIV and an STD becomes more contagious for two reasons. They can first infect their sexual partner with another pathogen that increases the probability of a transmission event. Second, the inflammation associated with an STD causes the person who has both HIV and an STD to become more contagious. There is at least one study that suggests that you can break through your antiviral therapy when you get a superimposed STD. STDs are really important players in increasing the efficiency of transmission of HIV.
However, several studies that treat STDs in a community have failed to reduce incident infections of HIV. This has caused great consternation and lack of confidence. But the problem is not that STDs are not important. The problem is that to effectively change the community level of HIV through treatment of STDs requires something incredibly special -- treating the right STD with the right drugs at just the right time for the right duration of time. This has been very difficult to accomplish.
Robert Bank: I have heard you speak at numerous conferences over the years and you are one of the leaders in thinking about HIV treatment and prevention and connecting them. With respect to the trials and the work that you have done in your career, what is it that keeps you going?
Dr. Cohen: I have been inspired by visible progress. In 1985 we started an infectious disease ward committed to the care of HIV patients but all we could do was treat opportunistic infections. At that time about 10% of all the beds at University of North Carolina (UNC) hospital were occupied by patients with HIV infections, and we had a high mortality rate. Fast forward 20 years and we rarely have to admit patients with HIV to the hospital because of the massive advances in treatment. As we work more internationally, our challenge is to bring the same benefit to people who live outside the United States.
Robert Bank: I want to end by saying that it is extremely inspiring to hear your passion and it is helpful because it gives people a lot of perspective around how far we've come. You once stated that with respect to the HIV Vaccine, its discovery is analogous to the builders who built the beautiful cathedrals in England -- that they never actually got to see them completed in their lifetimes. Do you still believe that to be the case for us?
Dr. Cohen: We have not yet succeeded in making a vaccine. We have two key possibilities: to develop a strategy where exposure evokes neutralizing antibodies or cell mediated protection so great that the exposed person will not acquire HIV.
As an alternative, cell mediated immunity might not prevent infection, but would lower HIV in blood and genital secretions to such a great extent that the disease cannot progress and the person is rendered less contagious. The bottom line is we have no choice but to make an HIV vaccine no matter how long it takes.
Myron Cohen, M.D., is Associate Vice Chancellor for Global Health and Director of the Institute of Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill.
Robert E. Bank, Esq., is Chief Operating Officer at GMHC. This interview was conducted in December, 2008.
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