HIV Drug Helps Block Herpes Virus

by U.S. Medicine

December 7, 2011

HIV Drug Helps Block Herpes Virus

A recent discovery by NIH researchers has shown the mechanism by which an anti-HIV drug can stop the spread of the virus that causes genital herpes. Tenofovir, when applied as a vaginal gel, damages a key enzyme in the herpes virus, short-circuiting its ability to replicate.1

A study released last year by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) showed that the tenofovir gel — an antiretroviral microbicide, showed that the gel reduced HIV infection by between 39% and 54% overall, depending on adherence. The study, which was published recently, also found that fewer women using tenofovir developed herpes, compared with the placebo group (29 compared to 58).

This was considered by the researchers to be an excellent secondary effect, because women with genital herpes are more likely to become infected by HIV.

Tenofovir also can be taken orally to inhibit reproduction of HIV. However, the oral version of the drug has not been shown to block the herpes simplex virus (HSV). Recently, the NIH announced the discontinuation of a tenofovir gel study because the gel was not more effective than placebo in preventing HIV.

“HIV infection is closely associated with herpes viral infection. When people with genital herpes are exposed to HIV, they are more likely to become infected than are people who do not carry the herpes virus,” said Leonid Margolis, PhD, head of the Section on Intercellular Interactions at the National Institute of Child Health and Human Development, Bethesda, MD, and one of the authors of the study.

Margolis and his collaborators examined the effects of tenofovir in a variety of tissue samples. They found that, after 12 days, levels of the HSV virus were between 1% and 13% of the virus level in untreated tissue. Tenofovir also blocked viral reproduction in tissue that was infected simultaneously by HIV and HSV.

Use of the gel in mouse models infected with HSV showed that the drug prevented symptoms and prolonged the animal’s survival.

The comparative potency of the vaginal gel compared with the oral form of the drug explains why the anti-HSV effects were not noticed sooner, Margolis said. The amount of tenofovir on tissues is 100 times greater when using the gel, compared with the drug taken orally.

1: Andrei G, Lisco A, Vanpouille C, Introini A, Balestra E, van den Oord J, Cihlar T, Perno CF, Snoeck R, Margolis L, Balzarini J. Topical Tenofovir, a Microbicide Effective against HIV, Inhibits Herpes Simplex Virus-2 Replication. Cell Host Microbe. 2011 Oct 4;10(4):379-89. PubMed PMID: 22018238; PubMed Central PMCID: PMC3201796.

Body Fluid Exposures Still Dangerous, Despite Prevention Efforts

Occupational exposures to blood and body fluids remain a danger, despite the increase in preventive measures over the past decade, according to research performed by the Infectious Disease and Infection Control office at the Washington VA Medical Center (DCVAMC).1

Researchers reviewed data from 1999 to 2008 at the DCVAMC, finding 564 incidents of occupational exposure to blood and body fluid (BBF). Of those, 66% were caused by needle sticks and 20% by sharp objects — two of the exposure methods targeted by prevention measures.

Exposures occurred most often in the acute-care setting, which accounted for 39% of exposures, and the operating room, which accounted for 22%. Housestaff accounted for the highest number of all exposure (35%), with 15.2 exposures per 100 housestaff.

The exposure rate remained steady during those 10 years, despite the increased use of anti-exposure devices and provider-education programs. The researchers concluded that targeting the specific occupational groups and hospital settings that have shown the highest risk should become a foundation of future preventive strategies.

1: Treakle AM, Schultz M, Giannakos GP, Joyce PC, Gordin FM. Evaluating a decade of exposures to blood and body fluids in an inner-city teaching hospital. Infect Control Hosp Epidemiol. 2011 Sep;32(9):903-7. PubMed PMID: 21828971.

HIV Drug Helps Block Herpes Virus Cont.

H5N1 Vaccine More Effective with DNA Primer

Response to the H5N1 avian influenza vaccine was enhanced when adult test subjects were primed with a DNA vaccine expressing a gene for a key H5N1 protein, according to research from the National Institute of Allergy and Infectious Diseases (NIAID).1

Volunteers who received the DNA vaccine 24 weeks before receiving a booster vaccine made from whole, inactivated H5N1 virus produced higher levels of antibodies that protect against influenza.

Developing an effective H5N1 vaccine has been difficult, because vaccines created from the whole, inactive virus have produced only modest amounts of antibodies.

“Our study was designed to test whether a gene-based DNA vaccine could prime the immune system and lead to a better antibody response following boosting with an inactivated H5N1 vaccine,” said, Julie Ledgerwood, DO, co-lead author of the new report and the study’s principal investigator. “We found that the DNA-primer vaccine improved the response to the inactivated H5N1 vaccine, but only when the boost interval was increased to 24 weeks.”

Of the 26 volunteers who received the vaccines 24 weeks apart, 21 produced antibodies at levels researchers believed were high enough to protect them from the virus. Those levels were four times higher than the groups who received two doses of inactive virus vaccine with no DNA-primer vaccine. Of those volunteers who received the DNA prime four weeks before the flu vaccine, only 4 out of 15 produced protective levels of antibodies.

The research team is planning a larger trial looking at the effectiveness of a DNA primer to help improve antibody creation for seasonal influenza. 

1: Lidgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, McTamney PM, Pearce MB, Yassine HM, Boynton JC, Bailer R, Tumpey TM, Koup RA, Mascola JR, Nobel GJ, Graham BS; the VRC 306 Study Team. DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis. 2011 Oct 3. [Epub ahead of print] PubMed PMID: 21975270.

Adherence to HCV Therapy Increases Virologic Response, Falters Over Time

Adherence to hepatitis C virus (HCV) therapy is directly related to an early and sustained virologic response, but that adherence falters over time, according to researchers at Perelman School of Medicine at the University of Pennsylvania, Philadelphia.1

Looking at data from the VA’s HCV clinical-case registry, researchers showed that early-virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks of treatment.

However, the researchers saw a pattern found in many chronic disease treatment programs. Adherence dropped over time — between 3% and 6% for every 12-week interval. This kind of drop is especially seen in treatments that require a large number of pills daily. The newer varieties of antiviral drugs call for pills to be taken every eight hours, creating “pill-fatigue” among patients, the researchers said.

One way to counteract poor adherence could be to address side-effects from HCV drugs. Patients who received treatment for thyroid dysfunction, anemia or low white-blood-cell count had a higher adherence to antiviral therapy.

The study was funded by NIH, VA and the Agency for Healthcare Research and Quality.

1: Lo Re V 3rd, Teal V, Locale AR, Amorosa VK, Kaplan DE, Gross R. Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study. Ann Intern Med. 2011 Sep 20;155(6):353-60. PubMed PMID: 21930852.

Organizational Culture Impacts MRSA Prevention

The culture of an individual hospital is key in implementing measures designed to prevent methicillin-resistant Staphylococcus aureus (MRSA), according to VA researchers. 1

Cross-sectional surveys were distributed to 16 medical centers assessing organizational culture and knowledge, attitudes and prevention practices. The final sample included 2,314 surveys (43% completed by nurses, 9% by physicians, and 48% by other healthcare personnel).

After analyzing the surveys, researchers found three factors account for the majority of prevention variance between facilities — staff engagement, hospital leadership and the amount of stress and feelings of being overwhelmed. Higher hospital leadership scores were associated with better hand hygiene, fewer reported barriers and more positive attitudes among staff. High levels of stress were associated with poorer prevention practices, more barriers and more negative attitudes.

These factors seemed to have greater impact on nurses and nonphysician healthcare personnel, the study found.

The researchers concluded that, in the future, when creating a prevention program, VA should focus not only on how organizational culture can impact a program, but create programs that target specific healthcare personnel in different ways.

1: Sinkowitz-Cochran RL, Burkitt KH, Cuerdon T, Harrison C, Gao S, Scott Obrosky D, Jain R, Fine MJ, Jernigan JA. The associations between organizational culture and knowledge, attitudes, and practices in a multicenter Veterans Affairs quality improvement initiative to prevent methicillin-resistant Staphylococcus aureus. Am J Infect Control. 2011 Aug 22. [Epub ahead of print] PubMed PMID: 21864944.

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