PrimeCuts: This Week in the Journals

December 7, 2009

winterJoshua Strauss MD

Faculty peer reviewed

The weather in the Northeast dipped below freezing over the weekend, along with our first snowfall of the season.  Breaking out the heavy coats, scarves and gloves, we have become acutely aware that the winter is fast approaching.  This also means that we are still in the midst of flu season.  Of course, this flu season is not a typical one, with the country worrying about both the seasonal flu as well as the pandemic H1N1 virus. 

On Saturday, the NY Times published an article featuring the CDC’s recent news briefing on the H1N1 vaccine1.  The director of the CDC explained that, having arrived at the two month mark since the vaccine’s introduction, we now have access to preliminary data demonstrating the vaccine’s safety, with a side effect profile similar to that of the seasonal flu vaccine. This new data can have great clinical import if we use it in our clinics to urge at-risk patients to accept the H1N1 vaccine. 

Perhaps partially as a consequence of widespread vaccination, a WHO official stated on Thursday that H1N1 infections continued to decrease in the United States and Canada in the past week2. This was no occasion to celebrate the end of the pandemic, though, as various countries in the northern hemisphere continue to experience spikes in H1N1 incidence.  In a cautious tone, Dr. Keiji Fukuda acknowledged that we may ultimately view this pandemic as mild in comparison to previous pandemics, but he believes it is still too early to tell.  He noted that the H1N1 virus continues to evolve, poses new challenges, and raises new concerns – “we continue to face ongoing uncertainties about the pandemic,” he said.  Readdressing a concern raised at last week’s briefing, Dr. Fukuda reiterated that while there “have been some clusters of oseltamavir resistance occurring in people who are severely immuno-compromised,” the vast majority of viruses remain sensitive to the drug…thankfully.

Given H1N1′s continued susceptibility to Tamiflu at this time, Dr. Tim Uyeki from the CDC writes on the New England Journal of Medicine’s website3 that “empirical antiviral treatment should be started as soon as possible for hospitalized patients with suspected 2009 H1N1.”  He noted several cases where Tamiflu was withheld from patients because of negative diagnostic testing. ” A negative RIDT (rapid influenza diagnostic test) or DFA (direct immunofluorescence assay) result does not exclude 2009 H1N1 virus infection,” he writes.   Additionally, clinicians should not wait for results from viral PCR before initiating antiviral treatment.   This has significant implications for our emergency rooms and outpatient clinics; we must take care to understand the low sensitivity of initial H1N1 diagnostic testing, and we must treat patients for whom we have high clinical suspicion, despite negative tests.

As World AIDS Day was December 1st, the other antivirals that had significant coverage in the journals this past week were antiretrovirals.  In conjunction with observing the day, the WHO updated its HIV guidelines for the first time since 20064. The WHO now advocates antiretroviral treatment for CD4 counts at or below 350 cells/mm3, whether or not they are associated with clinical symptoms; the 2006 guidelines had established the threshold at 200 cells/mm3.  This new recommendation is based on moderate evidence and follows data from pooled studies which demonstrate that doing so will reduce overall mortality in infected, asymptomatic, ART naive patients. WHO also stressed the necessity of routine CD4 and viral load monitoring to determine the appropriate time to initiate therapy.  Finally, WHO expands measures to prevent HIV transmission from mother to child during pregnancy and breastfeeding.

Once the decision has been made to initiate antiretrovirals, what grouping of meds should be used? In this week’s NEJM, Sax et al5 compare two different combinations of nucleoside reverse transcriptase inhibitors.  In a prospective trial, the combination of tenofovir DF-emtricitabine was significantly less likely to lead to initial virologic failure than was abacavir-lamivudine.  These findings may well have important implications for the choice of initial drug therapy in treating HIV infection.

While we are still perfecting treatment regimens, the Holy Grail of infectious disease remains the HIV vaccine.  In the same issue of NEJM, the lead article6 describes a study involving more than 16,000 largely heterosexual subjects in Thailand who were administered a vaccine regimen against HIV.  The results of the trial were largely disappointing, showing only minimal efficacy against HIV acquisition and no effects on subsequent viral load in those who became infected.  As Dr. Raphael Dolin writes in the accompanying editorial7, the important contribution here is in how it will direct further vaccine research.  Unfortunately, the Holy Grail still seems to be several years out of our reach.

While we won’t have an HIV vaccine any time soon, there is certainly ample work to be done globally, as well as in our own hospitals, to prevent HIV transmission.  President Jacob Zuma of South Africa deserves our applause for stepping up to the plate this week and committing his country to fight HIV with all available medications and resources8,9.  This is quite an about-face from a man who once joked that HIV transmission could be prevented by showering after sexual intercourse.

And finally, we must work harder to prevent transmission of infection in our own hospitals.  A troubling study brought to light by the NY Times and published in the December issue of Academic Medicine10,11 surveyed 699 recent medical school graduates, of whom 59 percent claimed they had been stuck by a needle at some point during medical school!  This number is astoundingly high and it follows that thousands of students are being put at risk for contracting HIV and Hepatitis C on a daily basis.  We must work harder to minimize sharps in surgeries and procedures, as well as improve education in handling sharps. Lastly, we must create an environment where students who have had the bad luck of sustaining a stick can be expedited through the treatment process, and be confident that reporting a needle stick will not have a deleterious effect on their grades and careers.

Dr Strauss is a first year resident in internal medicine at NYU Medical Center.

Peer reviewed by Cara Litvin MD, Executive Editor, Clinical Correlations

1.         Grady, Denise. “Review Shows Safety of H1N1 Vaccine, Officials Say” 4 December 2009. The New York Times.

2.         Transcript of virtual press conference with Dr. Keiji Fukuda, Special Adviser to the Director General on Pandemic Influenza, World Health Organization. 3 December 2009.   http://www.who.int/mediacentre/multimedia/vpc_transcript_3_december_09_fukuda.pdf

3.        Uyeki T. Diagnostic Testing for 2009 Pandemic Influenza A (H1N1) Virus Infection in Hospitalized Patients. N Engl J Med 2009.

4.        Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents. 30 November 2009. http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf

5.        Sax PE, Tierney C, Collier AC, et al. Abacavir-Lamivudine versus Tenofovir-Emtricitabine for Initial HIV-1 Therapy. N Engl J Med 2009;361:2230-40.

6.       Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. N Engl J Med 2009;361:2209-20.

7.       Dolin R. HIV Vaccine Trial Results — An Opening for Further Research. N Engl J Med 2009;361:2279-80.

8.     The Associated Press. “South Africa to Offer Free AIDS Drugs to Babies.” 1 December 2009. The New York Times.

9.     The L. HIV/AIDS: a new South Africa takes responsibility. Lancet 5 December 2009.

10.       Sharma GK, Gilson MM, Nathan H, Makary MA. Needlestick Injuries Among Medical Students: Incidence and Implications. Academic Medicine 2009;84:1815-21

11.      Parker-Pope, Tara. “A Silent Epidemic of Needle Injuries” 3 December 2009. The New York Times.

One Response to PrimeCuts: This Week in the Journals

  1. Danielle Savitsky on December 12, 2009 at 2:37 pm

    Informative and well written. I enjoyed the piece.

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