Stanford resistance mutation sheet

Frequently updated, the Stanford HIV database posts lists of clinically relevant mutations on its website that can be downloaded. The link is:

http://hivdb.stanford.edu/pages/download/resistanceMutations_handout.pdf

- Christopher Hurt

Viral decay curve

Once you start someone on ARVs, there's a predictable decline in viral load associated with it. This article from Nature Medicine has a nice figure, showing that different cell populations actually give rise to different portions of the decay curve, and as each replication within each "compartment" of cell type gets shut off by ARVs, that population's contribution to the viral load trails off, leading to the curve. (Hopefully it'll make better sense when you look at the figure!)

http://www.nature.com/nm/journal/v9/n7/fig_tab/nm0703-853_F2.html
from (http://www.nature.com/nm/journal/v9/n7/full/nm0703-853.html)

- Christopher Hurt

Map of Moore Regional

For people heading down to Pinehurst, here's the map of Moore Regional Hospital:

http://www.firsthealth.org/PDF/maps/MRH_internal.pdf

- Christopher Hurt

Super cool HIV interactive graphic

The New England Journal published the studies of raltegravir's use/efficacy for patients with an optimized background regimen (OBR) recently, and it turns out they also had an online-only interactive graphic that would be great for teaching students and residents visiting on the service. It's online at:

http://content.nejm.org/content/vol359/issue4/images/data/339/DC2/AIDS_Interactive.shtml

Enjoy!

– Christopher Hurt, MD

Sexual Assaults and PEP

There is a protocol that can be obtained from Lynda Bell in clinic regarding the care of survivors of sexual assaults. We will sometimes be called to weigh in on HIV PEP alone, as they have a protocol they follow for everything else. However, if you are ever called about what should be done, particularly if a SANE nurse is not available, here are some basics from the protocol.

Baseline laboratory tests should include:

• HIV Antibody testing
• CBC with differential
• LFTs
• BUN/Creatinine
• STD Screen (gonorrhea, chlamydia, syphilis)
• Hepatitis B serology
• Hepatitis C serology
• Pregnancy test

Prophylaxis against the most frequently diagnosed STDs among sexually assaulted women should be administered:

• Ceftriaxone 125mg IM in a single dose [Gonorrhea]
• Metronidazole 2gms orally in a single dose [BV, Trichomoniasis]
• Azithromycin 1gm orally in a single dose OR Doxycycline 100mg orally twice daily for seven days [Chlamydia]

HIV post-exposure prophylaxis is offered within 72 hours of the assault. If the perpetrator's HIV medical history is unknown, the two preferred regimens are:

• NNRTI-based: Efavirenz plus (Lamivudine or Emtricitabine) plus (Zidovudine or Tenofovir)...usually as Sustiva plus Combivir, or Sustiva plus Truvada.
• PI-based: Lopinavir/Ritonavir (Kaletra), plus Zidovudine or Tenofovir...usually as Kaletra plus Combivir, or Kaletra plus Truvada.

I've been advised typically to use the PI-based regimen unless there is another reason they should be avoided. Keep in mind that if the source patient (in the case of needlesticks) is one of OUR HIV clinic patients, we have access to their genotype and med history, and can formulate an appropriate PEP for the victim based on this information (i.e. you wouldn't want to start someone on PEP that their virus would be resistant to).

All sexual assault cases should follow up with a mid-level provider in the ID Clinic, regardless of whether or not they accept PEP. We usually just send a phone message to Lynda Bell with the patient's general information, and she contacts them to set up a follow up within 48 hours or so.

Risk Assessment

Sometimes, you are asked to comment on the risk, given different exposures (assault, blood splashes in the eye, needlestick, etc.). The risk for HIV acquisition per various acts can be found in the MMWR, January 21, 2005). It is also estimated in the Sanford Guide for the treatment of HIV.

Vaccinations in PEP

Hepatitis B: Patients who are unvaccinated prior to the assault should receive the initial Hep B vaccine, and follow up to complete the series. Unless the offender is known to have Acute Hep B, HBIG is not required. Remember, all patients should have serologies drawn.

Tetanus: If the patient has skin abrasions or other wounds and immunization status is greater than 5 years, give Tetanus Toxoid 0.5ml IM. If the patient has never been immunized, also give Hyper-Tetanus 250mcg IM.

Yvonne Carter, MD

Review of PPDs

We have a lot to learn regarding TB, but regarding the targeted testing for latent tuberculosis infection, here is a VERY QUICK review of what constitues a positive PPD:

>0 mm is considered a positive reaction if the patient:

• Is HIV-positive or immunocompromised AND are recent contacts to known or suspected infectious TB disease, regardless of previous treatment of LTBI
• Is HIV-positive with fibrotic changes on CXR consistent with prior TB who have received inadequate or no treatment for TB disease
• Is a child <5>

>5 mm is considered a positive reaction if the patient:

• Is HIV-positive
• Is a contact to known or suspected infectious TB case identified within the last two years
• Has fibrotic changes on CXR consistent with prior TB and have received inadequate or no treatment for TB disease
• Is Immunocompromised (receiving >15mg per day of Prednisone for one month, other immunosuppressive drugs, organ transplant recipients, persons taking TNF inhibitors)

>10 mm is considered a positive reaction if the patient:

• Is foreign-born from Asia, Africa, Carribean, Latin America, Mexico, South America, Pacific Islands, or Eastern Europe)
• Has converted their TST within two years
• Has a medical condition placing them at high-risk for TB Disease (DM, CRI, Chronic malabsorption syndrome, Leukemias and Lymphomas, Cancer of the head and neck, Silicosis, Weight loss of >10% ideal body weight, gastrectomy or intestinal bypass)
• Is an injection drug or crack cocaine user
• Is a child <4>
• Works in a mycobacterial lab

*Also, this cutoff is used per the clinicians judgement for: residents of long-term care facilities and homeless shelters, are inmates in the DOC, OR are employees in prisons/jails, long-term care facilities, hospitals/health care facilities, adult day-care centers for HIV patients, homeless shelters).

>15 mm is considered a positive reaction if the patient:

• Has NO risk factors for TB

Hope this helps!

Yvonne Carter, MD

HIV, Syphilis, and When to LP

Syphilis is a significantly prevalent STD in North Carolina, particularly in the setting of co-infection with HIV. Screening for syphilis is reviewed in the Syphilis Screening section of the blog. But, a common question that must be addressed in this circumstance is:

When is it necessary to perform an LP in to rule out Neurosyphilis in the HIV-positive patient?

The answer has many answers, but the commonly accepted answer is as follows: "All neurologically asymptomatic HIV-infected patients whose serum RPR titer is greater than or equal to 1:32 should undergo lumbar puncture regardless of syphilis stage." And, of course, any symptomatic HIV-patient with a history of syphilis should undergo LP to rule out Neurosyphilis.

This recommendation is taken from two main studies:

• Marra, et al. J Infect Dis 2004; 189: 369 - 376.
• Libois, et al. Sex Transm Dis 2006. HIV and syphilis: When to perform a lumbar puncture.

Yvonne Carter, MD

MRSA, MRSA me, Staph ain't what it used to be...

Apologies for the title, I couldn't help myself.  :)

ORSA comes up a lot, specifically how to decolonize patients with community-acquired ORSA (CA-ORSA). The UNC hospital epi people put together a brochure, which is sometimes hard to locate. I found this PDF online, from Kaiser Permanente out in California, which outlines I think what's pretty standard for us around here:

http://www.kplearning.com/10_national_site/uploads/B1S3.pdf

Johns Hopkins used to publish this nice periodic newsletter on HIV issues, but they've discontinued it due to time and budget constraints. Nevertheless, there was a nice article in the September 2004 edition that addressed CA-ORSA:

http://www.hopkins-hivguide.org/images/publications/nl_04_sept.pdf

The only caveat I'd put on this is, please know that the conventional dosing of TMP/SMX (Bactrim™, Septra™) at one DS tablet twice a day (as in the Hopkins thing) is now considered insufficient for ORSA treatment (at least around here, anyway). You need TWO DS tabs twice daily, and make sure you adjust for renal function, if reduced.

In general, we use doxycycline as our second-line agent, followed by clindamycin. Our micro lab will report clindamycin susceptibility separate from erythromycin – but outside labs may not be as reliable. Remember that CA-ORSA may have inducible resistance to the lincosamides (of which clinda is one) that won't show up in microdilution susceptibility testing used in outside hospitals and labs. You can't detect this is unless a "D-test" is performed, with both an e-mycin (15 µg)  and a clinda (2 µg) disk dropped onto the plate:

If the bug has inducible resistance, there'll be a flattening of the zone of inhibition between the two disks, suggesting that the bugs closer to the e-mycin disk have switched on their inducible resistance genes and are now laughing at the silliness of you attempting to use clindamycin to kill them.

Editorial note: The acronym "MRSA," for methicillin-resistant Staphylococcus aureus, is a humongo misnomer, since we don't use methicillin for resistance testing, and haven't in many years. Oxacillin is used on the plates, not methicillin – so you may hear it referred to more often in the micro lab as ORSA, and more often in the community as MRSA. If you're an ID purist, go with ORSA and look smart when someone asks what the hell it is that you're saying. (Or look like a big know-it-all dork. :)   )

 

– Christopher Hurt

Osteomyelitis...

... is the bane of the consult service existence. Well, along with the entire Family Medicine service, most of surgery, the impossibly perky OB-Gyn residents... but I digress. But osteo pretty much sucks. The question comes up pretty often, how do we best diagnose osteomyelitis, especially in the diabetic foot patients? This question was answered I think pretty comprehensively in the August 15, 2008 issue of Clinical Infectious Diseases. You can read it here, through UNC:

http://www.journals.uchicago.edu.libproxy.lib.unc.edu/doi/full/10.1086/590011

and the little editorial blurb that followed it is here:

http://www.journals.uchicago.edu.libproxy.lib.unc.edu/doi/full/10.1086/590012

– Christopher Hurt

Malaria prevention

Malaria stuff we get hit with pretty regularly, especially by student health in the summertime when lots of undergrads and grad students go globe-trotting. The New England Journal published a pretty helpful article in August 2008, on malaria prevention in short-term travelers. You can access it through UNC at:

http://content.nejm.org.libproxy.lib.unc.edu/cgi/content/full/359/6/603

(Plus it has a really sweet picture of the life cycle of malaria, along with where the drugs work.)

– Christopher Hurt