A reader adds to the growing discussion thread:

I feel I should chime in on the discussion of PrEP as a HIV prevention strategy. I’ve just gotten enrolled in the PrEP demonstration project put on through UCSF and the San Francisco city Tenofovirclinic. Your reader who had a month-long course of PEP probably took Combivir, which is a much harsher drug than Truvada. A few folks in my social circle have also gotten on board, and although this is anecdotal, I know of nobody who has stopped taking the drugs because of side effects. I’ve been encouraged about the efficacy of PrEP from the conversations I’ve had with clinicians and volunteers, and there are a lot of folks who are very excited about PrEP.

This is my second week on PrEP, and after a bit of nausea and an upset stomach the first week, the side effects have basically dissipated. The clinicians tell me that when folks do experience side effects, nearly all patients report that after the first month the side effects have gone away. It should also be reiterated that Truvada has been approved by the FDA for this purpose, so it’s not as if the promotion of PrEP is some wild-eyed, off-label drug use.

Another:

I’m a Ph.D. student, in my fourth year, studying viral evolution. In a nutshell, our lab studies emergent viruses – viruses that jump from one host species to another and often cause disease in the new host. While I don’t specifically study retroviruses, other members of the lab do, and I’m pretty well versed in the population genetics of disease emergence and resistance.

Coming from this background, my gut reaction is that preventative treatment with anti-retrovirals is a really bad idea. The reason is simple: you can’t trust people to take medication exactly as they’re directed, and this promotes the spread of resistant strains of viruses/bacteria/etc.

Most people are familiar with this concept because of our overuse and misuse of antibiotics. Someone gets sick, takes antibiotics for a few days, feels better, and stops before the treatment is done. They’ve eliminated most of the bacterial population that made them sick. However, the fraction that’s left is composed of individuals that survived the antibiotic treatment. Those bacteria may or may not be resistant to that drug. This doesn’t mean immune; at some dosage or duration, the drug will still kill them. But it takes more or longer. A curtailed treatment regimen fails to clear that threshold for some fraction of the bacterial population.

These resistant strains normally aren’t common because they tend to be less fit than non-resistant strains. They grow more slowly, require more resources, etc, which makes them less competitive than the non-resistant, or wild-type, individuals in the absence of antibiotics. But remove those individuals with three days of what should have been a five-day course of antibiotics, and the resistant part of the population can now flourish, since they don’t have to compete with the non-resistant strains. Next time that individual gets sick, the entire population is resistant, and treatment with a higher dose, a longer duration, or a new drug is required. Over the long term, this is a BIG problem (see TB, gonorrhea, MRSA, malaria, the list goes on and on).

The situation for viruses is pretty much the same, with a few wrinkles. First, viruses evolve faster. Retroviruses are at the high end of the spectrum, though not at the peak. Fast-evolving viral populations, like HIV, harbor a high degree of within-host genetic diversity, meaning that within any one infected person, there are many, many slightly-different strains of HIV, increasing the likelihood that a resistant strain is present.

Bacterial infections are usually treated with a single drug, at least until resistance is identified, while HIV is treated with a combination, as you know. This should make the presence of a resistant strain, one resistant to every drug present, less likely. And such an emergence is an extremely low-probability event.

The problem with the proposed preventative treatment, as I see it, is that while it doesn’t make the presence of such a strain any more likely, it greatly increases the likelihood of it spreading through the intra-host population, should it appear, for the same reason resistant bacteria can take over after an incomplete course of antibiotics. In this case, failure to adhere to the anti-retroviral regimen would allow multiply-resistant strains of HIV to circulate in the absence of competition from non-resistant strains.

Initially, this would probably happen at low levels, but as the proportions of each strain shifted in favor of the resistant strain, the treatment could conceivably cease to be affective. It’s possible, and I’d say probable, that over time, a resistant strain (probably slow-spreading and with low virulence, due to the trade-offs involved with resistance), previously found very rarely within individuals, might be found and transmitted with much greater frequency.

I could go on and on thinking about this for hours, but I’ll stop there. The short short version is that people don’t take medication as directed, which has led directly to multiply-resistant forms of many diseases. Preventively prescribing anti-retrovirals is just asking for history to repeat itself.

Update from a reader:

Re: the Ph.D. student’s concerns: He’s absolutely right. A researcher here at the University of Nebraska Medical Center has said much the same thing, which is why he is working on weekly or twice-monthly injections, rather than a regimen of pills, which could be stopped or forgotten. It’s currently only in animal trials, but it works: The latest breakthrough in the project is that the ART injection proved successful both as a treatment in HIV-infected mice, and as a preventive measure to keep healthy mice from contracting the virus. The news of Truvada broke just as he had a major paper coming out, and it garnered most of the attention. As he said: different drugs, different routes of administration, different formulations, but the goals are the same. But, he’s talking about a shot every other week, and you’re done, thus taking all the perils of a daily pill off the table. More info here and here.

A much more personal perspective:

I just wanted to take a moment to thank you for writing your post on PrEP and bringing this back into light. In the past 14 months about five friends of mine have seroconverted. The consistent level of HIV infections in my community shocks me considering the fact that many could have possibly been protected simply by taking a pill. Not to mention the fact that most of them had the means to cover the cost of the prescription.

In January I had a close brush with HIV, after a partner seroconverted 10 days after we had sex, and 15 days after a negative HIV test for both of us (which we didn’t have the results on yet). We had played bare in the past, but I preferred using a condom pending the result of HIV test. This close call caused me to become more serious and look into PrEP. What I was not prepared for was a complete lack of information and resources for gay men in Austin, Texas considering PrEP as an option. I found nothing regarding PrEP on Aids Services of Austin resource pages, and not the on the local city/county health web sites I had to rely heavily on friends from Seattle for advice and point me to better information.

I had to change from a doctor I had thought would be very good for me and my unique health needs as a gay man. My doctor’s nurse actively dissuaded me from requesting an appointment after I told her my intention was to seek PrEP. Even though I believed that I was a good candidate for PrEP based on my research. She said that he probably wouldn’t be comfortable prescribing this course of meds, and suggested I find a doctor with an HIV specialty.

So I did, and after all was said and done, I found a new doctor that I’m more confident he will be able to address my needs. So my point is … why is it so damn hard for those that seek PrEP to get it? Isn’t the goal to curb transmission and treat the positive?

This week, a good friend found out he slept with a guy in late May, didn’t use protection, and his partner just tested positive. My friend had flu-like symptoms and went to the doctor. His results were negative, but he’s still within the window period for anti-body testing. Once again, he knew about PrEP, but didn’t have the information make it happen.