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Limitations and Policy Implications
Several factors including cost, vaccination stigma, and acquired resistance limit the effectiveness of antiviral therapies. These issues are explored via a health policy perspective.

Research and prices
Rising Costs

Cost is an important factor that limits access to antivirals therapies in the United States and internationally. The recommended treatment regimen for hepatitis C virus infection, for example, includes sofosbuvir-velpatasvir (Epclusa) and ledipasvir-sofosbuvir (Harrvoni). A twelve week supply of these drugs amount to $113,400 and $89,712, respectively. These drugs can be manufactured generically at a cost of $100 - $250 per 12 week treatment. Pharmaceutical companies attribute the majority of these costs to research and development expenses. On average, the research and development costs required to bring a new drug to market amount to $17.2 billion. However, critics point to monopolistic market conditions that allow manufacturers to increase prices without facing a reduction in sales, leading to higher profits at patient's expense. Intellectual property laws, anti-importation policies, and the slow pace of FDA review limit alternative options. Recently, private-public research partnerships have been established to promote expedited, cost-effective research.

Vaccines and population health
While most antivirals treat viral infection, vaccines are a preemptive first line of defense against pathogens. Vaccination involves the introduction (i.e. via injection) of a small amount of typically inactivated or attenuated antigenic material to stimulate an individual’s immune system. The immune system responds by developing white blood cells to specifically combat the introduced pathogen, resulting in adaptive immunity. Vaccination in a population results in herd immunity and greatly improved population health, with significant reductions in viral infection and disease.

Vaccination policy
Vaccination policy in the United States consists of public and private vaccination requirements. For instance, public schools require students to receive vaccinations (termed “vaccination schedule”) for viruses such as diphtheria, pertussis, and tetanus (DTaP), measles, mumps, rubella (MMR), varicella (chickenpox), hepatitis B, rotavirus, polio, and more. Private institutions might require annual influenza vaccination. The Center for Disease Control and Prevention has estimated that routine immunization of newborns prevents about 42,000 deaths and 20 million cases of disease each year, saving about $13.6 billion.

Vaccination controversy
Despite their successes, there is plenty of stigma surrounding vaccines that cause people to be incompletely vaccinated. These “gaps” in vaccination result in unnecessary infection, death, and costs. There are two major reasons for incomplete vaccination: Although the American Academy of Pediatrics endorses universal immunization, they note that physicians should respect parents’ refusal to vaccinate their children after sufficient advising and provided the child does not face a significant risk of infection. Parents can also cite religious reasons to avoid public school vaccination mandates, but this reduces herd immunity and increases risk of viral infection.
 * 1) Vaccines, like other medical treatments, have a risk of causing serious complications in some individuals (i.e. severe allergic reactions). While these complications are less common than the risks faced when not vaccinated, negative media coverage can instill fear in a population. Other controversies involve the association of autism with vaccines, although the Center for Disease Control and Prevention, Institute of Medicine, and National Health Service regard this link as unfounded.
 * 2) 	Low vaccine-preventable disease rates as a result of herd immunity also make vaccines seem unnecessary and leave many unvaccinated.

Public policy
Use and Distribution

Guidelines regarding viral diagnoses and treatments change frequently and limit quality care. Even when physicians diagnose older patients with influenza, use of antiviral treatment can be low. Provider knowledge of antiviral therapies can improve patient care, especially in geriatric medicine. Furthermore, in local health departments (LHDs) with access to antivirals, guidelines may be unclear, causing delays in treatment. With time-sensitive therapies, delays could lead to lack of treatment. Overall, national guidelines regarding infection control and management standardize care and improve patient and health care worker safety. Guidelines such as those provided by the Centers for Disease Control and Prevention (CDC) during the 2009 flu pandemic caused by the H1N1 virus, recommend antiviral treatment regimens, clinical assessment algorithms for coordination of care, and antiviral chemoprophylaxis guidelines for exposed persons, among others. Roles of pharmacists and pharmacies have also expanded to meet the needs of public during public health emergencies.

Stockpiling

Public Health Emergency Preparedness initiatives are managed by the CDC via the Office of Public Health Preparedness and Response. Funds aim to support communities in preparing for public health emergencies, including pandemic influenza. Also managed by the CDC, the Strategic National Stockpile (SNS) consists of bulk quantities of medicines and supplies for use during such emergencies. Antiviral stockpiles prepare for shortages of antiviral medications in cases of public health emergencies. During the H1N1 pandemic in 2009-2010, guidelines for SNS use by local health departments was unclear, revealing gaps in antiviral planning. For example, local health departments that received antivirals from the SNS did not have transparent guidance on the use of the treatments. The gap made it difficult to create plans and policies for their use and future availabilities, causing delays in treatment.

Acquired resistance
Antiviral resistance can be defined by a decreased susceptibility to a drug through either a minimally effective, or completely ineffective, treatment response to prevent associated illnesses from a particular virus. The issue inevitably remains a major obstacle to antiviral therapy as it has developed to almost all specific and effective antimicrobials, including antiviral agents.

The Centers for Disease Control and Prevention (CDC) inclusively recommends those six months and older to get a yearly vaccination to protect from influenza A viruses (H1N1) and (H3N2) and up to two influenza B viruses (depending on the vaccination). Comprehensive protection starts by ensuring vaccinations are current and complete. The three FDA-approved neuraminidase antiviral flu drugs available in the United States, recommended by the CDC, include: oseltamivir (Tamiflu®), zanamivir (Relenza®), and peramivir (Rapivab®).

A study published in 2009 in Nature Biotechnology emphasized the urgent need for augmentation of oseltamivir (Tamiflu®) stockpiles with additional antiviral drugs including zanamivir (Relenza®). This finding was based on a performance evaluation of these drugs supposing the 2009 H1N1 'Swine Flu' neuraminidase (NA) were to acquire the Tamiflu-resistance (His274Tyr) mutation which is currently widespread in seasonal H1N1 strains.

Origin of antiviral resistance

The genetic makeup of viruses is constantly changing and therefore may alter the virus resistant to the treatments currently available. Viruses can become resistant through spontaneous or intermittent mechanisms throughout the course of an antiviral treatment. Immunocompromised patients, more often than immunocompetent patients, hospitalized with pneumonia are at the highest risk of developing oseltamivir resistance during treatment. Subsequent to exposure to someone else with the flu, those who received oseltamivir for “post-exposure prophylaxis” are also at higher risk of resistance.

Detection of antiviral resistance

National and international surveillance is performed by the CDC to determine effectiveness of the current FDA-approved antiviral flu drugs. Public health officials use this information to make current recommendations about the use of flu antiviral medications. WHO further recommends in-depth epidemiological investigations to control potential transmission of the resistant virus and prevent future progression. As novel treatments and detection techniques to antiviral resistance are enhanced so can the establishment of strategies to combat the inevitable emergence of antiviral resistance.