PEP, PrEP, or even PeEP?

I finally got around to reading the paper in the New England Journal on the use of daily antiretroviral therapy for the prevention of HIV infection (full text here). In hospital epidemiology we're very familiar with post-exposure prophylaxis (PEP) for healthcare workers who sustain percutaneous exposures or blood/body fluid exposures to mucous membranes. This paper evaluated pre-exposure prophylaxis (PrEP) for men who have sex with men by having the study subjects take a daily dose of truvada. New HIV infections were compared in the treatment group to men who were assigned to take a placebo daily. There were roughly 1200 men in each study arm. On average the men were in their late 20s, had more than 1 sex partner weekly, about 60% reported unprotected anal intercourse, and they were followed for roughly 1 year. There were 36 new HIV infections in the Truvada group (2.9%) and 64 new infections in the placebo group (5.3%). This represents a 44% relative risk reduction. Sounds pretty good, but that translates to only a 2.4% absolute risk reduction (the infection rate in the treated group subtracted from the infection rate in the placebo group). When the subset of men with detectable drugs levels (i.e., those who were compliant with Truvada) were compared to those without detectable drug levels, the relative risk reduction was 92%. "That's huge," exclaimed Dr. Anthony Fauci, the head of the National Institutes of Allergy and Infectious Diseases, in the New York Times.

So here we have an intervention that appears to be efficacious but not effective (that is, it works when you take the drug, but in the real world many people just won't take it--we've talked about this before). By my calculations, compliance appeared to be about 38% in the study. However, I think we can be sure that compliance would have been even less in the real world if the study subjects had to pay for the Truvada at the retail price of $13,000 yearly. We're also not told whether those who took the drug faithfully may have also been highly compliant with condom use, which may make the drug appear to be more effective than it actually is. So, in the end, I don't think that the impact of this study will be huge. In fact, I doubt it will have much impact at all. The real issue, it seems to me, is helping people to reduce risk the old fashioned way (fewer sexual partners and consistent use of condoms), until the day finally arrives when we have an effective vaccine for HIV.

Switching gears, as a hospital epidemiologist, I wondered if there is a role for PrEP in the hospital. Let's consider the case of a an untreated HIV infected patient with a high viral load who needs cardiac or orthopedic surgery soon. Should the operative team be given PrEP or perhaps peri-exposure prophylaxis (PeEP), with dosing the day before, the day of the procedure, and the day after? If I were the surgeon, I would be interested in that.

Been down so long...

being down don't bother me.  Having spent a few days here in Vancouver, I'm reminded of a paper published earlier this year out of British Columbia.  Gill et al, reported in CID results of a large 5422 person cohort of HIV+ patients with resistance testing during 1996-2008.  They described a drastic decrease in the incidence of new cases of HIV-1 drug resistance with the incidence rate of any newly detected resistance falling 12-fold from 1.73 cases per 100 person-months of therapy in 1997 to 0.13 cases per 100 person-months in 2008. I have posted Figure 1B below from the paper which shows declines in resistance to the major antiretroviral classes (PI, NRTI, NNRTI).

Isn't that amazing?  Wouldn't it be great if we could see the same thing in MDR-Gram negative bacterial pathogens?  Of course this won't happen, or at least won't anytime soon. Why would that be?  I think there are multiple reasons, but I think the major reason is that NIH and numerous other sources are funding HIV research to a much larger degree than anti-bacterial resistance research.  At the NIH, the funding disparity may be as high as 80 times.  In conversations, I've heard that NIH anti-bacterial resistance funding may be as low as $40 million/year compared to $3.2 billion/year for HIV research.  This comparison likely underestimates the disparity since pharmaceutical companies spend many multiples more on HIV antiretrovirals, because they are used chronically by patients over many decades.

I want to be clear that I'm not in favor of reducing what is spent on HIV research nor am I in favor of shifting funding from one infection to another.  Clearly that would be foolish and short-sighted as HIV AND antibacterial resistance are both problems of the next century. What I want to highlight is what can be accomplished with proper scientific inquiry, which is lacking in the "absence of evidenced-based medicine research" that exists in HAI prevention and antibacterial therapeutic choice.  Trip Gulick from Cornell mentioned yesterday at IDSA that there are now 10,000 possible 3-drug combinations of ART. Wouldn't it be great if we had similar choices and studies to utilize when we select antibiotics and duration of therapy for common bacterial infections. Quite frankly, you just get what you pay for.

I've been waiting 15 years for the tipping point, when we wake up and realize that bacterial resistance is a true public health emergency. However, I am increasingly concerned that we aren't waking up and responding in time.  Unfunded legislative mandates may make us feel like we're responding, but they will not solve much. We need to invest in our public health infrastructure and anti-bacterial discovery.  I just hope it's not too late.  What will surgery be like without effective antibiotics? We don't need to end up there if we follow the model put forth by the NIH and the cadre of investigators that have responded tirelessly to the challenge of HIV.  Let's face the antibacterial resistance challenge before it's too late.

Reference: Gill VS et al. Clin Infect Dis 2010

Hurry up, CDC

It has been a while since we blogged about the ridiculously stupid mask fiasco, mainly because the 2009 H1N1 virus is off the radar in most parts of the country and world.

This hasn’t stopped California OSHA from citing UCSF for not requiring N95 masks for the care of patients with suspected or confirmed 2009 H1N1. A post from the EIN this morning details the citation, which includes a fine and a requirement to rectify the situation by June 6, 2010. Here is a short excerpt from that EIN post:

I am…concerned about the short time window which we have been given to rectify the situation. Given the availability of 2009 H1N1 vaccine and increasing evidence in the literature that N95 masks are not superior to surgical masks, we plan to appeal before making a change in our practice; however, it is unlikely that OSHA will be willing to consider such an appeal without a formal change in the CDC guidance. I have heard that the CDC will soon be providing updated guidance on infection control practices for 2009 H1N1 - does anyone know the status of these guidelines and when they will be available?

Given that the “2009 H1N1” is going to be with us as a seasonal strain now, the CDC has only two options that make any logical sense: either back off the mistaken N95 recommendation, or begin requiring N95 use for all suspected or confirmed seasonal flu.

It would be nice if CDC acted quickly, and if OSHA held its fire until new guidance is issued.

Addendum: Rather than spending its time and resources doing post-hoc punishment of hospitals that responded appropriately to 2009 H1N1, California OSHA should be doing more to reduce the real threat of HIV transmission in the porn industry. So far, Cal OSHA has taken the bold step of “setting up an advisory committee to study the issue”.