Wednesday, March 20, 2013

A Cure for HIV?

Mural in Brussels
Here is a remarkable study by Sáez-Cirión and colleagues that was published this month in PLOS Pathogens. These authors looked at a group of 14 patients with HIV who received treatment early during infection and were able to maintain viral suppression even after coming off HIV medications. 

Historically, there has been controversy over when to start combined antiretroviral therapy (cART) for the treatment of HIV. Traditional arguments against starting cART early in infection included concern over possible long-term medication toxicity, cost and the development of drug-resistance. Arguments for early cART initiation include preserving immune function, reducing host viral reservoirs and limiting chronic immune activation. The study by ez-Cirión et al outlines another potential benefit: it is possible early therapy can lead to a "functional" HIV cure. 

Antiretrovirals have literally been life-saving to people living with HIV. Although these drugs suppress viral replication and allow for some amount of immune system recovery, in the vast majority of patients viral rebound and consequent immune system deterioration will occur rapidly once the drugs are removed. There are a small subset of patients (less than 1% of all HIV positive patients) who are, by virtue of gene differences, able to control the HIV virus to levels normally only achieved with cART (these patients are known as "HIV controllers"). 

Sáez-Cirión and colleagues examined a group of 14 patients who were discovered to have HIV very early in their infections and who were provided cART, and later came off cART. These patients behaved very much like "HIV controllers," although they did not have the gene distinctions that allow that group of patients to control HIV. As opposed to the typical scenario (where rebound viremia occurs quickly after cART cessation), these 14 patients demonstrated long-term viral suppression even off cART. These patients were dubbed "post-treatment controllers." The authors estimate that (among patients who are treated early in HIV infection) approximately 15% of patients receiving early HIV therapy may ultimately go on to have long-term viral suppression off cART. 

Although (early) post-treatment control of HIV does not truly represent a cure, for patients who benefit from this phenomenon this may represent a "functional" HIV cure. More study needs to go into this phenomenon and its implications for widespread HIV treatment and policy: will this phenomenon maintain over decades (not just years)? What are the implications of this for vaccine development? Certainly this implies that the immune system can be primed to efficiently control HIV: how can we capitalize on this via vaccination? How can we best identify patients with early HIV infection and get them into care immediately? What about the 85% of HIV positive patients who do not behave like post-treatment controllers?

The article by Sáez-Cirión and colleagues only further tips the scales in favor of early treatment. Antiretroviral drugs have become safer and easier to tolerate over the past decade, and as a result compliance with cART regimens has been easier to maintain. Recommendations for cART initiation have now fully shifted towards early therapy (see the most recent US national HIV treatment guidelines here), with therapy now recommended for all HIV positive patients regardless of immune status. With these new data implying that upwards of 15% of patients may be able to achieve a functional HIV cure with early cART initiation, identifying these patients early and getting them into care is more imperative than ever. 

Friday, March 15, 2013

VCU Medical Student Presents on Satisfaction with Brigade Care at CUGH Annual Conference

Kate Pearson, presenting at the Consortium
of Universities for Global Health's Annual
Conference, Washington, DC, March 14, 2013
Congratulations are in order to Kate Pearson, a third year VCU medical school student who presented her research on satisfaction with short-term medical brigade care at the Consortium of Universities for Global Health's annual conference in Washington, DC, yesterday.

Kate surveyed patients who received care at the Honduras Outreach Medical Brigada Relief Effort (HOMBRE)/ VCU Global Health and Health Disparities Program (GH2DP) clinics in the Department of Yoro, Honduras, in 2011. Her survey was a pilot project designed to identify key areas where we can improve the care we provide on our annual medical relief trips, as well as identify areas where we can bolster our health education efforts.

Twenty-three surveys were collected. Although the majority of patients noted satisfaction with the care provided, the survey helped to identify some key areas for future improvement. The majority of patients (70%, 16/23) desired more frequent clinics (2-3 times/ year), and the following were noted as areas to provide more health education: water purification (68%, 15/23), dental care (61%, 14/23), mental and emotional health (52%, 12/23) and nutrition (52%, 12/23).

Kate's data will help us target our health education messages on our upcoming May-June 2013 brigade, and will serve as a platform for a larger survey that will help us improve the care we provide.

Great work Kate!

Tuesday, March 12, 2013

The "Superbug" Problem: What Does the CDC's CRE Report Really Mean?

The Great Wave off Kanagawa (wikipedia,
Library of Congress)
Hi everyone! I am back after a long hiatus (vacation and lots of time on the medicine wards/ infectious disease consult service).

I was interviewed this morning by a local radio program about the "Superbug" problem and antibiotic resistance (you can find the interview here, if interested).

This interview was requested, in part, by the recent CDC report on carbapenem-resistant Enterobacteriaceae ("CRE"), and the media coverage that has followed the release of this disturbing report.

Enterobacteriaceae are a group of organisms that typically inhabit the gastrintestinal tract. They are a major problem, especially in hospitals, where they can cause urinary tract infections UTIs), bloodstream infections and wound infections.

CRE are extremely antibiotic resistant bacteria; in some cases these bacteria are resistant to all known antibiotics. Carbapenems are a class of antibiotics often reserved for the sickest, most unstable patients; unfortunately, for CRE, these agents do not work. Not surprisingly, CRE infections have been associated with very high mortality (upwards of 50%). In the case of many of these infections we truly are realizing the "post-antibiotic era," and a return to pre-20th century medicine.

The CDC report notes that during the first 6 months of 2012 nearly 5% of all hospitals reporting on healthcare-associated infections (in this case, UTIs and bloodstream infections) reported at least one CRE infection. When broken down by hospital type, a whopping 17.8% of long-term acute care hospitals reported one of these infections (almost 1 in 5 of all such facilities!). Overall, comparing data from 2001 and 2011, the percentage of Enterobacteriaeceae that were carbapenem-resistant (e.g, CRE) went from approximately 1% to 4%. Looking at one of these organisms in particular (Klebsiella) resistance went from 2 to 10%!

The reality in 2013 is that a person can be admitted to the hospital for a hip replacement, develop a UTI with CRE, and die from the UTI because there are no effective antibiotics to combat the infection. Unless we act now, and decisively, as a society/ global community, we truly are at risk of entering the post-antibiotic era.

In reading about this issue the CDC has some terrific information. For the best commentary I have seen I refer you to the posts over at Controversies in Hospital Infection Prevention.

Only time will tell whether we have the collective wisdom and will to preserve the antibiotics we have, develop new drugs and curb the emergence of antibiotic resistance. If the looming problem of pan-antibiotic resistant organisms is a tsunami, let us have the wisdom to heed the warning of the CDC's CRE report, and get to high ground. As it stands, I fear we will collectively be asleep in bed when the wave breaks.

Friday, March 1, 2013

Are We Entering an Era of Untreatable Gonorrhea?

Here is an excellent article on the growing problem of multi-drug resistant gonorrhea that was recently published in the CDC's Morbidity and Mortality Weekly Report (MMWR).

"Gonorrhea" refers to infection with the bacterium Neisseria gonorrhoeae and is a common sexually transmitted disease (over 300,000 cases were reported in the United States in 2011). Gonorrhea can cause significant morbidity: infertility, ectopic pregnancy, infection can facilitate HIV transmission, et cetera. One of the challenges in addressing gonorrhea as a public health problem is that many people who are infected have no symptoms; despite being asymptomatic, these individuals can still transmit the disease on to others.

Prevalence of ciprofloxacin resistance in urethral gonorrhea
isolates in US men, 1990-2007 (source:, MMWR)
Antimicrobial susceptibility results are not commonly available to clinicians who manage these infections. The infections, once identified are usually treated empirically with antibiotics known to be active against the bacterium. The challenge with this approach is that the organism has acquired resistance to the various antimicrobials we use to treat it. For example, we use to use flouroquinolone antibiotics to treat gonorrhea, but these antibiotics are no longer recommended due to high levels of fluoroquinolone resistance (see the graph above).

We currently are using cephalosporins (such as cefixime and ceftriaxone) to treat these infections, although resistance data is now suggesting that we are seeing some resistance emerge to these agents, as well. The problem here is that if we lose the cephalosporins there are no reliable alternative drugs we can use for these infections.

The authors of the MMWR report highlight the need to ramp up gonorrhea prevention efforts, to screen high-risk patients for gonorrhea "at least annually," to treat patients with appropriate doses of antimicrobials (per the CDC guidelines), and for clinicians to be vigilant in looking for cases of resistant gonorrhea.