Cost analysis of treatment strategies for the control of HSV-2 infection in the U.S.: A mathematical modeling-based case study.

Infection of Herpes Simplex Virus type 2 (HSV-2) is a lifelong sexually transmitted disease. According to the Center for Disease Control and Prevention (CDC), 11.9% of the United States (U.S.) population was infected with HSV-2 in 2015-2016. The HSV-2 pathogen establishes latent infections in neural cells and can reactivate causing lesions later in life, a strategy that increases pathogenicity and allows the virus to evade the immune system. HSV-2 infections are currently treated by Acyclovir only in the non-constitutional stage, marked by genital skin lesions and ulcers. However, patients in the constitutional stage expressing mild and common (with other diseases) symptoms, such as fever, itching and painful urination, remain difficult to detect and are untreated. In this study, we develop and analyze a mathematical model to study the transmission and control of HSV-2 among the U.S. population between the ages of 15-49 when there are options to treat individuals in different stages of their pathogenicity. In particular, the goals of this work are to study the effect on HSV-2 transmission dynamics and to evaluate and compare the cost-effectiveness of treating HSV-2 infections in both constitutional and non-constitutional stages (new strategy) against the current conventional treatment protocol for treating patients in the non-constitutional stage (current strategy). Our results distinguish model parameter regimes where each of the two treatment strategies can optimize the available resources and consequently gives the long-term reduced cost associated with each treatment and incidence. Moreover, we estimated that the public health cost of HSV-2 with the proposed most cost-effective treatment strategy would increase by approximately 1.63% in 4 years of implementation. However, in the same duration, early treatment via the new strategy will reduce HSV-2 incidence by 42.76% yearly and the reproduction number will decrease to 0.84 from its current estimate of 2.5. Thus, the proposed new strategy will be significantly cost-effective in controlling the transmission of HSV-2 if the strategy is properly implemented.

Prophylactic Efficacy Against Herpes Zoster and Costs Difference Between Acyclovir and Valaciclovir in Hematological Patients.

BACKGROUND: Immunocompromised hematological patients are at increased risk of herpes zoster (HZ). We examined the efficacy of acyclovir and valaciclovir in preventing HZ. We also created a simulation to reduce prophylactic medicine costs. PATIENTS AND METHODS: We retrospectively evaluated 573 hematological patients who received chemotherapy, and assessed the difference in the costs between the acyclovir (Zovirax®) and valaciclovir (Valtrex®) groups. RESULTS: Forty-four out of the 573 patients (7.7%) developed HZ. Out of them, there were 37 patients (84.1%) who received corticosteroids. Moreover, in total, there were 67 patients receiving acyclovir prophylaxis and 42 patients receiving valaciclovir prophylaxis, out of which one from each group occurred with HZ. The total 5-year cost of acyclovir and valaciclovir was ¥2,869,917 and ¥4,809,952, respectively. Therefore, by changing from valaciclovir to acyclovir, medical costs could be reduced by 28.3%. Additionally, switching to generic inexpensive acyclovir would possibly reduce them to 15.0%. CONCLUSION: Chemotherapy, including corticosteroids, is associated with a high incidence of HZ. Additionally, there was no prophylactic difference between acyclovir and valaciclovir. We expect that use of generic acyclovir could reduce prophylaxis costs by 85.0%.

Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective.

INTRODUCTION: Valganciclovir (vGCV) and valacyclovir (vACV) are used in cytomegalovirus (CMV) prophylaxis in renal transplant recipients. The aim of this study was to compare the economic impact of both regimens during 1-year follow-up. METHODS: A total of 117 renal transplant recipients at risk for CMV were randomized to 3-month prophylaxis either with vGCV (900 mg/day, n = 60) or vACV (8 g/day, n = 57) and their data used in a pharmacoeconomic analysis. The pharmacoeconomic evaluation involved all direct CMV-related expenses in the first year after transplantation. Sensitivity analysis was employed to examine the effects of various prices of antiviral drugs and diagnostic procedures on overall CMV-related costs. Simulation of the more expensive US healthcare perspective was performed, and a scenario involving costs of acute rejection (AR) was examined. RESULTS: Overall CMV-related costs were significantly lower in the vACV arm; median United States dollars (USD) 3473 (3108-3745) vs. USD 5810 (4409-6757; P < 0.001) per patient, respectively. Our data showed that the critical determinant of the major disparity between the prophylactic regimens was the prophylaxis price. Median cost of prophylaxis in the vACV group was USD 1729 (1527-2173) compared to USD 3968 (2683-4857) in the vGCV group (P < 0.001). In sensitivity analysis of the overall CMV-related costs, the least and the most expensive pharmacotherapy and diagnostic scenarios were used; nevertheless, the vACV arm remained markedly less expensive. Simulation considering the higher physician/nurse and hospitalization fees of the US healthcare system and the scenario including expenditure associated with AR episodes also favored vACV. CONCLUSION: VACV prophylaxis for CMV is associated with a significant 44% lower cost than vGCV at the first year after renal transplantation.

Valaciclovir versus aciclovir for the treatment of primary genital herpes simplex: a cost analysis.

The current guidelines for the treatment of primary herpes simplex in the Genito-urinary department in Sheffield Teaching Hospitals NHS Foundation Trust, recommend valaciclovir as a first-line medication. This is a prodrug of aciclovir, which has been used for many years as a treatment for primary herpes simplex virus. The basis of the recommendation largely relates to valaciclovir being more bioavailable than aciclovir. However, there is no evidence to suggest this has an effect on overall outcome with regard to symptom control and viral shedding. The purpose of the service evaluation was to discover if significant cost savings could be made by changing the prescribing policy to make aciclovir the drug of choice for primary herpes simplex virus. Based on 160 patients receiving valaciclovir (500 mg BD) during April 2013 and March 2014, if they had been treated with aciclovir (400 mg TDS) instead, a saving of £828.80 (66% reduction) could have been made.

The efficacy and cost-effectiveness of valacyclovir in cytomegalovirus prevention in solid organ transplantation.

Prevention of cytomegalovirus infection using antiviral prophylaxis or the pre-emptive therapy approach is an integral part of management of patients after solid organ transplantation. Regarding renal transplantation, valacyclovir is currently the only antiviral agent recommended for prophylaxis as an alternative to valganciclovir. This review article discusses studies documenting the efficacy and safety of valacyclovir prophylaxis as well as those comparing valacyclovir with other prophylactic regimens or with pre-emptive therapy. Also addressed are the economic aspects supporting the cost-effectiveness of valacyclovir prophylaxis and demonstrating lower costs compared with other cytomegalovirus preventive strategies.

Pharmacoeconomic impact of different regimens to prevent cytomegalovirus infection in renal transplant recipients.

BACKGROUND: The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation. METHODS: Hospitalization data and medical resource utilization data were prospectively collected alongside two randomized trials. In the first trial, the patients were randomized to 3-month prophylaxis with either oral ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the control group (n = 12) managed by deferred therapy. In the second trial, the patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia. The cost analysis involved all real costs directly related to CMV during the first year after renal transplantation. RESULTS: The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968, and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred therapy groups, respectively (p < 0.001). Valacyclovir prophylaxis was significantly less expensive than any other regimen. The cost of one episode of CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease, deferred therapy was the most expensive strategy (p < 0.001). CONCLUSIONS: Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.

The cost-effectiveness of herpes simplex virus-2 suppressive therapy with daily aciclovir for delaying HIV disease progression among HIV-1-infected women in South Africa.

BACKGROUND: The Partners in Prevention HSV/HIV transmission trial (Partners HSV/HIV Transmission Study) showed that herpes simplex virus-2 (HSV-2) suppressive therapy with daily aciclovir could decrease HIV disease progression amongst HIV-1/HSV-2 coinfected individuals. The cost-effectiveness of daily aciclovir for delaying HIV-1 disease progression in women not eligible for antiretroviral therapy (ART) is estimated. METHODS: Resource use/cost data for delivering daily aciclovir at a primary health care HIV clinic were collected in Johannesburg. Effectiveness estimates were obtained from the Partners HSV/HIV Transmission Study trial and epidemiologic data from South Africa. A Markov model simulated the cost-effectiveness of daily aciclovir on HIV-1 disease progression in ART-naive women. Therapy was given to all HIV-1-infected women. Cost-effectiveness was compared against cost per life-year gained (∼US $1200 per LYG) of ART provision in South Africa. RESULTS: For an ART eligibility criteria of CD4 count <200 cells/µL and the cheapest internationally available aciclovir (US $0.026 per day for 2 × 400 mg aciclovir), the median cost per LYG is US $1023 (95% confidence interval [CI]: 537-2842), whereas it decreases to US $737 (95% CI: 373-2489) if the ART eligibility criteria is CD4 count <350 cells/µL. Both these projections compare favorably with the estimated cost-effectiveness of ART in South Africa (∼US $1200 per LYG). The cost per LYG increases dramatically for the current aciclovir cost in South Africa (US $0.14 per day), if salary costs are higher and if HSV-2 prevalence amongst HIV-1-infected women are lower. Projections suggest HSV-2 suppressive therapy could dramatically increase the proportion of women initiating ART. CONCLUSIONS: HSV-2 suppressive therapy could be an affordable strategy for reducing HIV-1 disease progression and retaining women in care before ART initiation, but cheaply available aciclovir is needed.

Genital ulcer disease treatment policies and access to acyclovir in eight sub-Saharan African countries.

BACKGROUND: Herpes simplex virus-2, the most common cause of genital ulcer disease (GUD) globally, is a cofactor in human immunodeficiency virus type-1 (HIV-1) acquisition and transmission. Current World Health Organization guidelines for sexually transmitted infections recommend acyclovir as first-line syndromic treatment of GUD in countries with high herpes simplex virus-2 prevalence (> or =30%). OBJECTIVE: To assess the extent of adoption of acyclovir as syndromic treatment for GUD, and describe procurement, distribution, and cost of acyclovir in the public and private sectors of 8 sub-Saharan African countries. METHODS: We conducted standardized interviews with Ministry of Health (MoH) officials, pharmacists, and other pharmacy workers based in the public and private sectors. Interviews were conducted in Botswana, Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Price comparisons were conducted using the 2007 median international reference price (IRP) for acyclovir. RESULTS: Of the 8 African countries, 4 surveyed had adopted acyclovir as first-line syndromic GUD treatment in both their essential medical lists and sexually transmitted infection guidelines. Country-specific acquisition prices for acyclovir 200 mg were comparable to the median IRP and ranged from 0.74 to 1.95 times the median IRP. The median retail cost of acyclovir in the private sector ranged from 5.85 to 9.76 times the median IRP. Public health facilities faced cost and regulatory barriers that impeded the requisitioning of acyclovir from the central medical stores. CONCLUSIONS: Systems for drug procurement, distribution, and access in sub-Saharan African countries need strengthening for a GUD treatment policy using acyclovir to be effective.

Can preemptive cytomegalovirus monitoring be as effective as universal prophylaxis when implemented as the standard of care in patients at moderate risk?

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity, mortality, and cost in solid organ transplant recipients. This study was conducted to measure both the clinical efficacy and the pharmacoeconomic impact of implementing, as standard of care, an abbreviated preemptive monitoring strategy compared with universal prophylaxis in a large teaching hospital. METHODS: This prospective observational study included only recipients at moderate risk for CMV infection, specifically recipients who were CMV seropositive before transplant. Recipients transplanted between February 2006 and December 2006 received prophylactic valganciclovir for 90 days after transplant, and those transplanted between January 2007 and December 2007 were enrolled in a preemptive monitoring strategy that included no anti-CMV prophylaxis but instead used serial CMV polymerase chain reactions in weeks 4, 6, 8, 10, 12, 16, 20, and 24 to monitor the development of CMV DNAemia. Costs were analyzed from a societal perspective. RESULTS: A total of 130 patients were included in this study. Baseline and transplant demographics are well matched between groups. CMV syndrome occurred in three patients in each group, and one patient in the preemptive group developed CMV disease. Thirty-seven percent of patients in the preemptive group developed CMV DNAemia, 68% of these patients received antiviral therapy. Personnel and laboratory monitoring costs were significantly higher in the preemptive group, whereas medication cost was significantly higher in the prophylaxis group. CONCLUSIONS: Although outcomes and the overall cost of (1) universal prophylaxis and (2) preemptive monitoring are similar, universal prophylaxis places the cost burden on the patient whereas preemptive monitoring shifts the cost burden to the healthcare system.

Congenital anomalies and resource utilization in neonates infected with herpes simplex virus.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection, while uncommon, is associated with substantial morbidity and mortality. However, there is little nationally representative data describing resource utilization. METHODS: This retrospective cohort study was conducted using the Pediatric Health Information System, an administrative database that contains discharge diagnosis and resource utilization data from 35 free-standing children's hospitals. Patients

Economic evaluation of early administration of prednisolone and/or aciclovir for the treatment of Bell's palsy.

OBJECTIVES: Bell's palsy (BP), which causes facial paralysis, affects 11-40 people per 100 000 per annum in the UK. Its cause is unknown but as many as 30% of patients have continuing facial disfigurement, psychological difficulties and occasionally facial pain. We present an randomised controlled trial (RCT)-based economic evaluation of the early administration of steroids (prednisolone) and/or antivirals (acyclovir) compared to placebo, for treatment of BP. METHODS: The RCT was not powered to detect differences in the cost-effectiveness; therefore, we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [e.g. prednisolone only (PO) versus acyclovir only versus prednisolone and acyclovir versus placebo, prednisolone versus no prednisolone (NP) and acyclovir versus no acyclovir]. We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy. We used the percentage of individuals with a complete recovery (based on House-Brackmann grade = 1) at 9 months and Quality Adjusted Life Years (e.g. derived on responses to the Health Utilities Index III) as measures of effectiveness. Other parameter estimates were obtained from trial data. RESULTS: PO dominated-i.e. was less costly and more effective-all other therapy strategies in the four arms model [77% probability of cost-effective (CE)]. Moreover, Prednisolone dominated NP (77% probability of being CE at 30 000 UK pounds threshold) while no acyclovir dominated aciclovir (85% chance of CE), in the two arms models, respectively. CONCLUSIONS: Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE. Further data on costs and utilities would be useful to confirm findings.

Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days. DESIGN: Cost-effectiveness analysis. SETTING: Decision model. PATIENTS: Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis. INTERVENTIONS: Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures. MAIN OUTCOME MEASURES: Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained. RESULTS: Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained). CONCLUSIONS: Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation.

Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.

Analysis of the cost-effectiveness of varicella vaccine programmes based on an observational survey in the Latium region of Italy.

Varicella is the most widespread childhood disease in Italy. However, as in many parts of the world, the country does not yet have a unified approach to the management of the disease. A cost-effectiveness analysis of varicella vaccination strategies, using the Latium region in Italy as a case study, was undertaken. Mass vaccination is only recommended if the immunization programme can achieve coverage of over 85% in a short time. However, experience in Italy with non-compulsory vaccinations has shown this is difficult to achieve. Consequently, eradication of the disease is not seen as an attainable short-term goal. For mass varicella vaccination to be successful, it must be run at a national as well as regional level in combination with education programmes, and a reliable surveillance system. The interaction between varicella and herpes zoster must also be taken into account when considering vaccination strategies, as zoster vaccination strategies may have an impact on varicella coverage.

Acyclovir prophylaxis for pregnant women with a known history of herpes simplex virus: a cost-effectiveness analysis.

OBJECTIVE: Previous literature has shown acyclovir to be cost-effective as prophylaxis for women with genital symptomatic herpes simplex virus infection recurrence during pregnancy. We extend this analysis by adding quality-adjusted life year measurements and considering women with a diagnosed history of herpes simplex virus infection but without recurrence in pregnancy. STUDY DESIGN: A decision analytic model was designed that compared acyclovir prophylaxis versus no acyclovir for women with a history of diagnosed genital herpes simplex virus infection but without recurrence in pregnancy. Sensitivity analysis and Monte Carlo simulations were performed to test for robustness. RESULTS: We found that 22,286 women must be treated to prevent 1 neonatal death, 8985 women to prevent 1 affected child, and 177 women to prevent 1 cesarean delivery. As compared with no acyclovir, acyclovir prophylaxis at 36 weeks of gestation saves approximately dollar 20 per person and increases total quality-adjusted life years by 0.01. In univariate sensitivity analysis, this result was robust to all reasonable probability and quality-adjusted life year estimates. Monte Carlo simulation demonstrated acyclovir to be cost-effective 100% of the time and cost saving >99% of the time. CONCLUSION: Acyclovir prophylaxis versus no treatment for pregnant women with a diagnosed history of genital herpes simplex virus infection but without recurrence during pregnancy is cost-effective over a wide range of assumptions.