Use Of Antiviral Medications Research Articles

Time to Take Stock in HIV/AIDS Prevention

The first behavioral interventions designed to stem the spread of HIV were tested over 25 years ago, within just a few years of the first reported cases of AIDS. Interventions grounded in sound theories of behavior change have since been demonstrated effective at reducing high-risk injection and sexual practices in nearly every population with known risks for HIV/AIDS. Brief risk reduction counseling, small group skills building workshops, syringe exchange programs, enhanced HIV counseling and testing, interventions aimed at people living with HIV/AIDS, condom social marketing programs, peer influence models and other behavioral HIV prevention approaches have all shown efficacy in carefully controlled clinical and community trials. Meta-analyses repeatedly show that these interventions produce consistent positive behavioral outcomes and several have significantly reduced recurrent sexually transmitted infections. Unfortunately, behavioral interventions have also demanded considerable commitment to implement and resources to sustain. Despite their effectiveness, HIV risk reduction interventions have not provided the quick fix to the AIDS problem that so many policy and decision makers have sought for the past 20 years. In contrast to behavioral interventions, biomedical approaches to HIV prevention offer the promise of immunity, permanent reductions in susceptibility, and diminished infectiousness. By far, the most successful biomedical intervention for HIV prevention remains the use of antiretroviral medications for preventing mother-to-child transmission of HIV. Comprehensive mother-to-child transmission prevention programs have witnessed declines in HIV infected infants to levels approaching zero. For example, in New York there were nearly 100 HIV infected infants in 1997 whereas there were less than 10 in 2006. The number of HIV infected babies has similarly plummeted in Botswana where all pregnant women are tested and treated, whereas neighboring South Africa has been slow to implement mother-to-child prevention of HIV transmission and the country remains burdened by these avoidable and tragic infections. Several important clinical trials that are testing new biomedical HIV prevention interventions were launched in the early part of this decade and their results are now becoming available. Most encouraging has been the definitive findings from three randomized clinical trials of male circumcision for HIV risk reduction (Auvert et al. 2005; Bailey et al. 2007; Gray et al. 2007). These compelling studies all showed as much as a 60% reduction in HIV transmission among men who underwent circumcision, a magnitude of protection that cannot even be expected from most vaccine models. Male circumcision faces implementation challenges due to obvious cultural and religious meanings attached to circumcision, issues that individual communities have to sort out. But the effectiveness of male circumcision for preventing female-to-male HIV transmission is indisputable. The results of several other eagerly awaited biomedical prevention technologies have unfortunately been more disappointing. Based on a clear and convincing model of cervical susceptibility to HIV transmission, Nancy Padian conducted a critical study of the diaphragm for HIV prevention. The findings did not demonstrate added benefit from diaphragm use over and above supplying women with condoms and risk reduction counseling (Padian et al. 2007). In the past year we have also seen two promising vaginal microbicides, cellulose sulfate and Carraguard, fail to demonstrate efficacy. What was another innovative approach to preventing HIV transmission was use of antiviral medication to suppress Herpes Simplex Virus (HSV) S. C. Kalichman (&) University of Connecticut, Storrs, CT, USA e-mail: seth.k@uconn.edu

Urgent strategic research into influenza to inform health policy and protect the public

The Australian management plan for pandemic influenza (2005) highlighted a number of areas where more information may yield better plans for protecting Australia. In 2005, the National Health and Medical Research Council (NHMRC) developed a special "urgent research" funding program to meet those information needs as quickly as possible. The funding program resulted in grants totalling $6.5 million being awarded for 33 research projects, in five broad areas: Detection and identification of the virus; Vaccine development and evaluation; Antiviral medication use and effectiveness; Public health interventions; and Understanding behavioural responses to achieve effective communication and staged implementation of public health strategies. Outcomes of the program will be evaluated formally in 2007.

A National Survey of the Infectious Diseases Society of America Emerging Infections Network concerning Neuraminidase Inhibitor Prescription Practices and Pandemic Influenza Preparations

This report summarizes the findings of a national survey of infectious diseases consultants regarding their use of neuraminidase inhibitors and the status of their planning for an influenza pandemic. The respondents indicated that government stockpiles should be increased, that many have received requests for antiviral medications, and that additional recommendations regarding the appropriate use of antiviral medications would be helpful.

Respiratory syncytial virus: disease, development and treatment

Respiratory syncytial virus (RSV) is spread by droplets and causes infections of the upper and lower respiratory tract. It is most common in infants, children under the age of five years and the elderly. Due to the nature of the transmission, infections with RSV are contagious but usually short lived. Pharmacological treatment involves the use of antiviral medication. Nurses caring for older people, infants or young children should be aware of the risk of transmission of RSV, pathogenesis and treatment options available to effectively manage the care of patients.

Use of oseltamivir in Dutch nursing homes during the 2004–2005 influenza season

To assess the implementation of guidelines for using neuraminidase inhibitors in the control of influenza outbreaks in Dutch nursing homes, data were collected on prophylactic and therapeutic use of anti-viral medication, indications for use and criteria for prescribing, based on experiences during the influenza season 2004–2005 in a retrospective cross-sectional survey among Dutch nursing homes after the 2004–2005 season. Ninety/194 (49%) participating nursing homes reported an outbreak of influenza-like illness; in 57/194 (29%) influenza was laboratory confirmed. In 37/57 homes (65%) oseltamivir had been used as prophylaxis. Prophylactic use was extended to all residents and staff in 6/37 (16%) of homes, but limited in the others. In 9/37 (24%) no staff were issued prophylaxis. Among clinicians with laboratory confirmed influenza, 41/46 (89%) had used oseltamivir therapeutically. Main reasons for not prescribing oseltamivir for prophylaxis and/or therapy were lack of scientific evidence, high costs, and absent or delayed laboratory confirmation. Logistical bottlenecks in diagnosis, cost-effectiveness concerns, and lack of an evidence-base hamper full integration in policy and should be addressed.

Estimating influenza vaccine effectiveness in an outbreak when anti‐viral medications were used as a control measure

Objectives: To estimate influenza vaccine effectiveness (VE) from an outbreak of influenza A in an aged care facility in which neuraminidase inhibitors were used as part of outbreak control measures.Methods: The outbreak occurred between 25 December 2001 and 21 January 2002. Neuraminidase inhibitors were used to control the outbreak. Residents and staff with respiratory symptoms were tested for influenza using RT‐PCR and/or serology Vaccine effectiveness (VE) was estimated for the prevention of laboratory‐confirmed influenza.Results: Nineteen of 42 (45%) residents and four of 29 (14%) staff were laboratory‐confirmed as cases. The outbreak was caused by an influenza A (H3N2) strain, antigenically matched to that season's vaccine. The VE for preventing laboratory‐confirmed influenza infection was 61% (95% Cl 41 ‐73) among residents and 100% (95% Cl 63–100) among staff.Conclusions: The VE estimates calculated from this outbreak were consistent with other published results. Outbreaks of influenza in institutions provide a good opportunity to review influenza VE, but use of antiviral medications as control measures may affect interpretation of findings.

Oseltamivir (Tamiflu®) and its potential for use in the event of an influenza pandemic

Recent cross species transmission of avian influenza has highlighted the threat of pandemic influenza. Oseltamivir (Tamiflu) has been shown to be effective in the treatment and prevention of epidemic influenza infection in adults, adolescents and children (> or = 1 year). Although oseltamivir has not been approved for prophylactic use in children, it has been shown to be effective. Oseltamivir is also active against avian influenza virus strains. Evidence suggests that lower doses or shorter durations of treatment/chemoprophylaxis other than those approved may not be effective and may contribute to emergence of viral resistance. Safety data from dose ranging studies show that 5 day courses of 150 mg twice daily for treatment and 6 week courses of 75 mg twice daily for prophylaxis were as well tolerated as the approved dose regimens. The use of oseltamivir in a pandemic is influenced by the goals of the pandemic plan developed by the responsible Government and Health Authority. To optimize use of antiviral medications, processes will be needed to collect, collate and report outcome data from treated patients and/or from use for chemoprophylaxis of pandemic influenza during the first-wave outbreaks. If oseltamivir is included in a national or regional pandemic plan, stockpiling of the material, either in the form of capsules or the bulk active pharmaceutical ingredient will be necessary. In the absence of a stockpile, there is no guarantee that an adequate supply of oseltamivir will be available.

Summer outbreak of respiratory disease in an Australian prison due to an influenza A/Fujian/411/2002(H3N2)-like virus

An outbreak of influenza A occurred in a prison system in New South Wales, Australia in January 2003 during the southern hemisphere summer. This report documents only the third confirmed outbreak of influenza in a prison environment. The outbreak investigation included case ascertainment, state-wide surveillance, a case-control study and interventions to limit the outbreak such as infection control, quarantine, cohorting of cases, and the use of antiviral medication for prophylaxis. A total of 37 clinical cases were identified. Influenza A virus was detected in 11 of the 22 respiratory tract specimens collected. The virus was typed as an influenza A/Fujian/411/2002 (H3N2)-like virus. This strain subsequently became the predominant virus strain during the northern hemisphere winter and the following 2003 Australian southern hemisphere winter influenza season.

Facial nerve disorders committee: Controversies in facial paralysis

The management of facial nerve paralysis is a topic that stimulates considerable debate. Depending on the features of a given case, practitioners may advocate treatment options ranging from no intervention to urgent surgery. There is some validity to all treatment options; the key is understanding when features of a given case dictate a particular therapeutic approach. This miniseminar will address several topics related to management of facial paralysis including: (1) pitfalls in diagnosis of Bell’s palsy; (2) acute facial paralysis in pregnancy; (3) use of antiviral medications; (4) indications for and interpretation of electroneuronography (ENoG) and electromyography (EMG); (5) role of imaging studies; (6) indications, timing, and outcomes of decompression surgery; (7) techniques to aid recovery from acute facial paralysis; (8) botulinum toxin for rehabilitation; and (9) medical legal aspects of chronic facial paralysis. The format will include short presentations, panel discussion of interesting cases, and audience participation.

Cerebral blood flow pulsatility deficits in HIV+ poly substance abusers: differences associated with antiviral medications

This study examines the influence of HIV-seropositivity and antiviral medications on cerebral blood flow in cocaine abusers. Forty-five HIV negative (HIV−) cocaine abusers, 36 HIV positive (HIV+) cocaine abusers (CD4; mean 378, ±229) and 27 control HIV− subjects were studied. Blood flow velocity and pulsatility were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography (TCD). Psychological assessments, which included the psychiatric symptom checklist (SCL-90R), hopelessness (Beck) and well-being (Ellison) questionnaires revealed greater psychiatric distress in HIV+ cocaine abusers than the other groups. HIV− cocaine abusers and HIV+ cocaine abusers not receiving antiviral medications ( n=25 of 36) had elevated pulsatility values, indicating increased resistance in the cerebral blood vessels in comparison to control subjects. HIV+ cocaine abusers using antiviral medications ( n=11 of 36) had pulsatility values similar to HIV− control subjects. Interestingly, there was no significant relationship between intensity of psychiatric distress reported by HIV+ cocaine abusers and perfusion deficits. Our findings suggest that unmedicated HIV+ cocaine abusers have cerebrovascular deficits, which are similar to HIV− cocaine abusers. In addition, the use of antiviral medications appears to be associated with a reduction of these deficits in HIV+ cocaine abusers. Nevertheless, more studies will be needed before any conclusion can be reached regarding possible beneficial effects of these agents on the cerebral vasculature.

Dysregulation of Growth and Development in HIV-Infected Children

Growth dysregulation is quite common in HIV-infected children and growth failure is one of the most sensitive indicators of disease progression. Beginning at birth, HIV-infected infants often have smaller size and lower birthweight than noninfected children born to HIV-infected women. The causes of growth dysregulation are varied, and can be due to alterations in gastrointestinal function, chronic or repetitive infections, and alterations in metabolic and endocrine function. The metabolic and endocrine effects may be the consequence of the primary infection or secondary to the use of any of the medications required to treat HIV infection and its complications. Correlational studies have identified an inverse relationship between viral burden and linear growth and body mass index, i.e., the use of antiviral medications that reduce viral burden is associated with improvements in anthropometric indices of growth. Alterations in cytokine profiles, possibly related to reported abnormalities in thyroid indices, fat metabolism, and the somatomedin axis, may be indicative of dysregulation on a cellular level. Pubertal delay, especially among boys, is common, and may contribute to the overall growth failure associated with HIV infection. If the basis for growth failure resides in metabolic and regulatory abnormalities, then interventions beyond increasing caloric intake will be necessary to increase linear growth rate and reverse growth failure in HIV-infected children.

Anti-HIV Type 1 Cytotoxic T Lymphocyte Effector Activity and Disease Progression in the First 8 Years of HIV Type 1 Infection of Homosexual Men

Cytotoxic T lymphocytes (CTL) may play an important role in host defense against HIV-1 infection. In this study, we examined the responses of circulating effector CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of whom were asymptomatic and had documented time since seroconversion of < 8 years. CTLe responses to at least one of the four HIV-1 gene products were detected in 83% of the subjects. The magnitude and prevalence of the anti-Tat responses were significantly less than the responses to Gag, Pol, and Env. Cell depletion studies indicated that the lytic activity against the HIV-1 structural proteins was mediated by CD8+ T cells, although 30% of Env-specific lysis was mediated by CD16+ natural killer cells. Anti-HIV-1 CTLe responses against Gag and Pol were significantly less in subjects infected for over 6 years as compared to those infected for shorter periods of time. We found no correlation, however, between anti-HIV-1 CTLe responses and either CD4+ or CD8+ T cell counts, rates of CD4+ T cell loss, HIV-1 infectious viral load, use of antiviral medications, or subsequent progression to AIDS. Our results indicate that anti-HIV-1 CTLe activity is relatively stable in asymptomatic subjects infected < 6 years, and is not an early marker for risk of disease progression.

Coxsackie B-2 virus infection in rat beating heart cell culture

Beating rat heart cultures were prepared in vitro and infected with Coxsackie B-2 virus. The cells were evaluated in the post-infected period for changes in cardiac enzymes, alterations in beating frequency and cytotoxicity as measured by chromium 51 ( 51Cr) release. The cardiac enzymes, lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured in infected and uninfected controls over a period of 120 h. Enzyme levels in the infected cells remained essentially the same for the first 42 h as compared to the controls. At this time, the LDH levels increased rapidly reaching 116 ± 24.8 U/l while the controls remained at 46.9 ± 9.7 U/l. Aspartate aminotransferase levels increased at a slower rate and obtained a level of 104 ± 20.2 U/l compared to 66.6 ± 13.2 U/l in the control. Visual evidence of cellular damage as measured by decreased beating frequencies and the appearance of cytopathic effect was first noted at 42 h post-infection. Complete loss of cardiac beats and maximal viral cytopathic effect occurred at 96 h post-infection. Cardiac cellular damage as measured by cytotoxicity assay was found to parallel those changes seen in cardiac enzymes. No significant changes in cytotoxicity were observed for the first 24 h; however, at 48 h increased release of 51Cr was noted and visual evidence of viral replication also was present. The cardiac enzyme changes noted in beating rat heart cells appear to be similar to those changes reported in patients with viral-induced myocardial disease. This would suggest that the use of beating rat heart cultures can be a useful model in the study of viral-induced cardiac diseases, and may give insight into the use of anti-viral medications for the management of these disorders.