Can an ART a day keep the doctor away?

On November 23, 2010, in HIV/AIDS, prevention, research, by Karen Grepin

Interesting results of a trial that looked at the Pre-Exposure Prophylaxis (PrEP) – essentially uninfected people taking a drug prophylactically – on new infections from HIV were released earlier today in the New England Journal of Medicine.  Roughly 2500 male and transgender men who have sex with men (high risk uninfected) in the Americas, South Africa, and Thailand were randomized to receive a once daily combination pill of emtricitabine and tenofovir disoproxil fumarate (FTC–TDF).  After about a year and a half, about 100 people developed new infections from the virus but the treatment group experienced a roughly 44% decreased risk of new infection.  This is pretty exciting news, as there is a clearly the need for new effective methods to prevent HIV.

I know it is coming…so I’ll weigh in on this question.  So if this works, why not just distribute the drugs to everyone in highly affected countries?  While exciting news, I think there are a number of drawbacks of that might prevent this approach from being more widely adopted at the general population level.  
First, these are heavy drugs, the trial itself found relatively high levels of adherence problems, and I am not an expert in this but I’ve always had the impression that most ART drugs are not the kind of thing people want to be taking unless the alternative (death) is severe.  
Second, we need to consider the whether this represents a good use of resources. This trial was conducted in a very high risk population and even then the risk reduction was only about half.  Depending on how costly these drugs would be, plus the associated medical costs of ensuring some medical follow-up of people taking these drugs, it might not be cost-effective relative to other prevention strategies in the general population.  
Third, we must also consider drug resistance.  Although no drug resistance was detected among those patients who developed HIV during the trial, resistance to these particular medicines can be developed and could potentially have widespread effects on overall usefulness of ART medicines.
Fourth, we must also consider the behavioral effect of these drugs on patients.  The overall trial would have picked up short-term behavior effects (e.g. if people think they are protected they may engage in more or more risky sexual behavior) but we should worry about is the more long term effects of this intervention on behavior, say over time or outside of a trial setting.  Depending on how large this effects might be, it could undermine the overall effectiveness of the strategy.
Finally, PrEP is not a magic bullet.  There are other ways of becoming infected that are unlikely to be affected by this drug (e.g. injections) and the reduction was far from complete.  Plus, unlike other prevention methods (e.g. condoms) it does little to protect against other STIs.  
But of course anything that helps in preventing this horrible disease, even a bit,  is very good news.
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8 Responses to “Can an ART a day keep the doctor away?”

  1. Karen Grepin says:

    Can an ART a day keep the doctor away? http://bit.ly/efNcA3 #HIV #globalhealth

  2. RT @KarenGrepin: Can an ART a day keep the doctor away? http://bit.ly/efNcA3 #HIV #globalhealth

  3. Theo Smart says:

    Ironically, it might be just the opposite of keeping the doctor away… it could mean EVERYONE would have to visit the doctor/nurse (HIV positive and negative alike) either for treatment, or if negative, for a prescription for PREP. Then, they would have to be regularly tested for HIV to make sure they haven't unwittingly been or have become infected — in which case they would be taking sub-optimal treatment (this is only two ARVs) and at risk of becoming resistant to drugs they will need for treatment one day. Which, frankly sounds a little crazy.

    However, we shouldn't dismiss it out of hand. For the most at risk populations who are resistant to behaviour change, this is QUITE interesting. Another potential use is in campaigns. In high burden settings, a relatively brief period of universal PREP may be enough to interrupt the cycle of new infections that appear to drive the epidemic (people with acute infection are most likely to transmit the virus). Campaigns that combine intermittent PREP with universal (continuous) access to treatment (it can be debated whether that should be for everyone who is infected or only for those with advanced HIV) should be able to achieve sharp reductions in the number of new infections. I'm not saying that would be easy to implement, but we ought to model it at the very least. Models of "three months of abstinence" have suggested you could stop the epidemic quickly — the problem, of course, is getting people to go along with abstinence. Something like this might be as close as we can get to a vaccine for some time and could put a major dent in the number of people we would later have to put on lifelong treatment (and which we simply can't afford to do).

  4. shishir says:

    Let us treat ill one first.
    Patients who are in ART are less infective.So if we treat all HIV infected irrespective of their CD4 count we can minimise the rate at which HIV is spreading.
    shishir

  5. Theo Smart says:

    RT @KarenGrepin: Can an ART a day keep the doctor away? http://bit.ly/efNcA3 #HIV #globalhealth

  6. Karen Grepin says:

    @theosmart Thanks for comments, agree with the doctor argmt (I was being cliche) and find campaign idea intriguing: http://bit.ly/efNcA3

  7. Roger says:

    In agreement with Theo's first paragraph which is why I think the approach is facing some serious implementation issues even before starting (and the CDC has already issued a guideline!).

    Now disagreinge with "For the most at risk populations who are resistant to behaviour change, this is QUITE interesting."

    So because I am resistant to behaviour change and Dr Prevention has failed to convince me that my life and that of other was of any value I should therefore be allowed to carry on with my selfish "resistant" behaviour?

    Can we really carry on accepting such behaviours? Nowadays there are many behaviours that we don't tolerate anymore, it should not be any different in the present case.

    We give in too easily I am affraid.

    all the best.

  8. Brian Hanley says:

    Let's first assume 90% effectiveness, but since it's drug based, that means that we have a repeating interval, not classical sterilizing immunity (the goal of good vaccines).

    On a study interval basis we have a median of 1.2 years, and a maximum of 2.8 years. Leaving aside that the study could have done a swipe at a longitudinal analysis of rate, let's project this out over 10 years using known values.

    10 years / 1.2 years per interval = 8.3 intervals.
    0.9^8.3 = 0.42 or 42% which is the best outcome (and somewhat implausible). That isn't bad. But, over the 30 year most active sex period, there would be 25 intervals. That best result gives a 30 year effectiveness of roughly 7%. One can quibble with this 7% number, since sexual activity is not flat from 15 to 45, and sex work declines in the 20's in Thailand, but I argue the change isn't large enough overall in these target groups. (Admittedly, I have not proven this. For those who want to argue, one study I heard presented at Gladstone cited an average of roughly 200 contacts per seroconversion.)

    Second, let's look at what the study showed for general effectiveness and project that 44% forward.
    0.44^8.3 = 0.001 or 0.1%, using the average outcome for the study. (And keep in mind that people adhere better to regimens during trials.)
    Let's make an indefensible presumption, that all people at risk for HIV take this therapy. In 2006, CDC estimated roughly 45,000 new cases. Thus, we should expect approximately 45 HIV cases avoided over 10 years. This number is within the range of estimation error.

    That indicates that most probably, over a 10 year period, there will be no provable effect of this therapy from a public health point of view.

    And if we work it out over the 30 year lifetime, then 0.44^25 = 1.2e-9, a good approximation of zero.

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