ICEID: TCAD regimen shows promise against H3N2 flu variant

ATLANTA – Triple combination antiviral drug therapy offers a broad-spectrum treatment option for H3N2 variant influenza virus, according to findings from an in vitro study.

The finding suggest that the combination could play an important role in the event of an influenza pandemic, Carrie Sitz reported in a poster at the International Conference on Emerging Infectious Diseases.

CDC/Dr. Michael Shaw; Doug Jordan, M.A.

After a human infection with the novel A/H3N2 variant was reported in 2011, and trivalent inactivated influenza vaccine was found to be of limited use, as it provided protection against H3N2 but not the H3N2 variant (H3N2v) in ferrets and elicited cross-protection against H3N2 in young adults but not older adults or children, a triple combination antiviral therapy (TCAD) regimen was considered.

Amantadine, oseltamivir carboxylate, and ribavirin each were tested alone and in double and triple combinations against the novel H3N2 variant virus carrying genes from avian, swine, and human origins. Triple therapy achieved a therapeutic effect with lower doses of component drugs, compared with monotherapies of antivirals as single agents, said Ms. Sitz, a microbiology research assistant at the Naval Health Research Center, San Diego.

The agents, which each have different mechanisms of action and which function at distinct points in the virus life cycle, were tested using the various combinations in 96-well plates seeded with Madin-Darby Canine Kidney (MDCK) epithelial cells. They were found to produce synergistic antiviral activity, she noted.

A control experiment in the absence of the drugs also was performed.

Of note, amantadine had no activity as a single agent against H3N2v, even at 100 mcg/mL, the highest dose tested. However, amantadine did contribute to the synergy of the TCAD regimen. This effect was concentration dependent; the potential synergy volume increased steadily and significantly from about 300 to about 450, to about 575, and to about 600 as the amantadine concentration increased from +0.32, to +1.0, to +3.2, to +10, Ms. Sitz noted, adding that this may indicate that amantadine, which is known to have widespread resistance, can still play a therapeutic role in the setting of the TCAD regimen.

Vaccines are usually an effective safeguard against seasonal influenza but may be inadequate in seasons when a novel influenza emerges, resulting in compromised standard of care for treating the emergent viruses, she said, noting that this is especially true in immunocompromised patients.

“These issues point to the likelihood that we may be unprepared for a novel influenza virus displaying both virulence and transmissibility,” she added.

The current findings suggest that TCAD, which has previously been shown to be effective against seasonal and H5 influenza strains, is a broad-spectrum treatment option that could potentially play a role in pandemic preparedness. The mechanism by which oseltamivir carboxylate and ribavirin potentiate amantadine in combination therapy is unknown, and further testing is needed for evaluation, she concluded.

This study was sponsored by the Armed Forces Health Surveillance Center. The authors reported having no conflicts of interest.

[email protected]

ATLANTA – Triple combination antiviral drug therapy offers a broad-spectrum treatment option for H3N2 variant influenza virus, according to findings from an in vitro study.

The finding suggest that the combination could play an important role in the event of an influenza pandemic, Carrie Sitz reported in a poster at the International Conference on Emerging Infectious Diseases.

CDC/Dr. Michael Shaw; Doug Jordan, M.A.

After a human infection with the novel A/H3N2 variant was reported in 2011, and trivalent inactivated influenza vaccine was found to be of limited use, as it provided protection against H3N2 but not the H3N2 variant (H3N2v) in ferrets and elicited cross-protection against H3N2 in young adults but not older adults or children, a triple combination antiviral therapy (TCAD) regimen was considered.

Amantadine, oseltamivir carboxylate, and ribavirin each were tested alone and in double and triple combinations against the novel H3N2 variant virus carrying genes from avian, swine, and human origins. Triple therapy achieved a therapeutic effect with lower doses of component drugs, compared with monotherapies of antivirals as single agents, said Ms. Sitz, a microbiology research assistant at the Naval Health Research Center, San Diego.

The agents, which each have different mechanisms of action and which function at distinct points in the virus life cycle, were tested using the various combinations in 96-well plates seeded with Madin-Darby Canine Kidney (MDCK) epithelial cells. They were found to produce synergistic antiviral activity, she noted.

A control experiment in the absence of the drugs also was performed.

Of note, amantadine had no activity as a single agent against H3N2v, even at 100 mcg/mL, the highest dose tested. However, amantadine did contribute to the synergy of the TCAD regimen. This effect was concentration dependent; the potential synergy volume increased steadily and significantly from about 300 to about 450, to about 575, and to about 600 as the amantadine concentration increased from +0.32, to +1.0, to +3.2, to +10, Ms. Sitz noted, adding that this may indicate that amantadine, which is known to have widespread resistance, can still play a therapeutic role in the setting of the TCAD regimen.

Vaccines are usually an effective safeguard against seasonal influenza but may be inadequate in seasons when a novel influenza emerges, resulting in compromised standard of care for treating the emergent viruses, she said, noting that this is especially true in immunocompromised patients.

“These issues point to the likelihood that we may be unprepared for a novel influenza virus displaying both virulence and transmissibility,” she added.

The current findings suggest that TCAD, which has previously been shown to be effective against seasonal and H5 influenza strains, is a broad-spectrum treatment option that could potentially play a role in pandemic preparedness. The mechanism by which oseltamivir carboxylate and ribavirin potentiate amantadine in combination therapy is unknown, and further testing is needed for evaluation, she concluded.

This study was sponsored by the Armed Forces Health Surveillance Center. The authors reported having no conflicts of interest.

[email protected]

ATLANTA – Triple combination antiviral drug therapy offers a broad-spectrum treatment option for H3N2 variant influenza virus, according to findings from an in vitro study.

The finding suggest that the combination could play an important role in the event of an influenza pandemic, Carrie Sitz reported in a poster at the International Conference on Emerging Infectious Diseases.

CDC/Dr. Michael Shaw; Doug Jordan, M.A.

After a human infection with the novel A/H3N2 variant was reported in 2011, and trivalent inactivated influenza vaccine was found to be of limited use, as it provided protection against H3N2 but not the H3N2 variant (H3N2v) in ferrets and elicited cross-protection against H3N2 in young adults but not older adults or children, a triple combination antiviral therapy (TCAD) regimen was considered.

Amantadine, oseltamivir carboxylate, and ribavirin each were tested alone and in double and triple combinations against the novel H3N2 variant virus carrying genes from avian, swine, and human origins. Triple therapy achieved a therapeutic effect with lower doses of component drugs, compared with monotherapies of antivirals as single agents, said Ms. Sitz, a microbiology research assistant at the Naval Health Research Center, San Diego.

The agents, which each have different mechanisms of action and which function at distinct points in the virus life cycle, were tested using the various combinations in 96-well plates seeded with Madin-Darby Canine Kidney (MDCK) epithelial cells. They were found to produce synergistic antiviral activity, she noted.

A control experiment in the absence of the drugs also was performed.

Of note, amantadine had no activity as a single agent against H3N2v, even at 100 mcg/mL, the highest dose tested. However, amantadine did contribute to the synergy of the TCAD regimen. This effect was concentration dependent; the potential synergy volume increased steadily and significantly from about 300 to about 450, to about 575, and to about 600 as the amantadine concentration increased from +0.32, to +1.0, to +3.2, to +10, Ms. Sitz noted, adding that this may indicate that amantadine, which is known to have widespread resistance, can still play a therapeutic role in the setting of the TCAD regimen.

Vaccines are usually an effective safeguard against seasonal influenza but may be inadequate in seasons when a novel influenza emerges, resulting in compromised standard of care for treating the emergent viruses, she said, noting that this is especially true in immunocompromised patients.

“These issues point to the likelihood that we may be unprepared for a novel influenza virus displaying both virulence and transmissibility,” she added.

The current findings suggest that TCAD, which has previously been shown to be effective against seasonal and H5 influenza strains, is a broad-spectrum treatment option that could potentially play a role in pandemic preparedness. The mechanism by which oseltamivir carboxylate and ribavirin potentiate amantadine in combination therapy is unknown, and further testing is needed for evaluation, she concluded.

This study was sponsored by the Armed Forces Health Surveillance Center. The authors reported having no conflicts of interest.

[email protected]