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HIV Cure possible?

Dec 28, 2003

Dear Dr. Pierone,

Thanks for your insight. Your optimism is appreciated and reflects an impressive combination of realism and "the glass is half full" outlook. First of all after a Medline search I found some interesting data on Prostratin and was wondering if you think it will ever be possible to eradicate HIV. Though in clinical terms it is not even on the horizon, I am confused... One one hand the literature I read said it is impossible to cure a disease caused by a virus that embeds itself in the genome such as HIV. One the other hand Dr. Brown and others at NIH and AMFAR have appraoched eradication (first marking the sanctuary sites for destruction then purging them) as a possiblity. Also it looks as though from what I hear that genetic engineering holds much promise for curing HIV and institutions like MIT are researching as I write this. I think they are using riRNA.

Surely it is not possible to cure HIV (although there was whispers of this initially in 1997) with current treatments, though I'll have to say as a pithy college student with a rudimentary knowledge of science it is astounding that HAART is as efficacious as it is. I think it is also due to the reslience of the CD4s and CD8s. But within the past six years treatment has been marked by breakthrough drugs like SUSTIVA and EPIVIR. Unprecendented. Many with NHL have still have to battle through CHOP like they did in the 1970s. Still, don't most docs agree that patients cannot be on the ARV drugs forever, even for over a decade. Newer treatments will simplify regimins even more but this gets back to my original question. If the USA spent the 70billion on defense instead on research in Virology, then we would see eradication, right? It is not like we see people living longer with war. Unlike medical progress, one that broadens people's horizons

Thanks for your time

Response from Dr. Pierone

Hello, thanks for you post. What does cure mean in the context of an infectious disease? What we mean by cure is that one takes a therapy or series of treatments for a demarcated period of time and after this treatment is completed, the condition does not come back. This might involve one dose of diflucan to cure a vaginal yeast infection in a healthy female or one year of arduous interferon-based treatment for hepatitis C.

If, in order to cure HIV, we have to extirpate every dormant HIV genome from every piece of human DNA in which it is secreted, then we likely have an insurmountable problem. But, what if we could leave the dormant HIV genome in place, but find a way to block the molecular events that enable it to become activated and infectious? This would involve genetic engineering and gene therapy techniques. For example, if the genetic targets of HIV activation can be identified, activation gene blocking sequences developed, these blocking sequences linked to a vector, delivery via vector to latently infected cells, and incorporation of blocking sequences to latently infected genomes. If this could be done, this strategy might prevent dormant HIV DNA from ever activating and in effect, produce a "cure". Maybe the purging experiments that you mentioned could be part of this process by diminishing the burden of latently infected cells that need to be gummed up. In any case, gene therapy approaches are extremely exciting (for other diseases as well) but are years away from reality for "cure" of HIV infection.

Absent a cure, can people with HIV infection be expected to take antiretrovirals every day for over a decade? I think this is not an unrealistic expectation. We treat people with hypertension for decades and don't think twice about it. The first generation blood pressure medications from the 1950's had horrendous side effects and were not particularly effective (sound familiar?). We should expect ongoing incremental advances in the side effect profile of antiretrovirals and this will make long-term therapy less challenging.

On the other hand, perhaps decade-long continuous treatment for HIV infection may not be necessary. One study underway is the SMART study, which is exploring the possibility of CD4 count driven treatment. In this trial, half of the participants receive antiretroviral therapy when CD4 counts drop below 250 and stop medications when counts rise above 350. This will result is a series of treatment interruptions lasting from months to years in this arm of the study. The rest of the volunteers will receive continuous treatment with antiretrovirals with the intention to maintain viral suppression. This study may help elucidate how chronic HIV infection ought to be treated.

Another wild card that could transform HIV management is the potential for therapeutic vaccines. If the powerful and targeted forces of the immune system could be brought to bear against the virus this might permit more time off medications and still allow long-term control of HIV. All in all, it is difficult to predict what will happen decades hence in HIV management.

Maybe not 70 billion on virology, but I think at a minimum the United States should be spending tens of billions right now to save people in underdeveloped parts of the world that are dying of preventable and treatable diseases like HIV. Beyond the immediate humanitarian benefits, this investment would go a long way towards stabilization of societies and should lessen the risk of violence and terrorism.

abacavir and alcohol
A warning about high viral loads

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