Cost-effectiveness and budget impact of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa

2020 ◽  
Author(s):  
Jacqui Miot ◽  
Trudy Leong ◽  
Simbarashe Takuva ◽  
Andrew Parrish ◽  
Halima Dawood

Abstract Background Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135 000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. Methods A decision analytic cost-effectiveness and budget impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered four treatment arms: (a) standard of care; 2-week course of amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course of amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) and (d) oral course; 2-week oral fluconazole/flucytosine (oral). A sensitivity analysis was conducted on key variables. Results The highest total treatment costs were in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, then the 1-week AmBd/5FC with the lowest cost in the standard of care arm. Compared to standard of care the 1-week flucytosine course is most cost-effective at USD31/QALY, followed by the oral 2-week course at USD155/QALY and the 2-week flucytosine course at USD568/QALY. The budget impact analysis shows that the 1-week course has the lowest incremental cost, followed by the oral course and then the 2-week flucytosine course compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to the price of flucytosine and hospital costs, particularly length of stay. Conclusions The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective regardless of whether it is used as a 1-week, 2-week or oral regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jacqui Miot ◽  
Trudy Leong ◽  
Simbarashe Takuva ◽  
Andrew Parrish ◽  
Halima Dawood

Abstract Background Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135,000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. Methods A decision analytic cost-effectiveness and cost impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered five treatment arms: (a) standard of care; 2-week course amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) (d) oral course; 2-week oral fluconazole/flucytosine (oral) and e) 1-week course amphotericin B/fluconazole (1wk AmBd/Flu). A sensitivity analysis was conducted on key variables. Results The highest total treatment costs are in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, the 1-week AmBd/5FC, then standard of care with the lowest cost in the 1-week AmBd/Flu arm. Compared to the lowest cost option the 1-week flucytosine course is most cost-effective at USD119/QALY. The cost impact analysis shows that the 1-week flucytosine course has an incremental cost of just over USD293 per patient per year compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to life expectancy and hospital costs, particularly infusion costs and length of stay. Conclusions The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective when it is used as a 1-week AmBd/5FC regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.


2020 ◽  
Author(s):  
Jacqui Miot ◽  
Trudy Leong ◽  
Simbarashe Takuva ◽  
Andrew Parrish ◽  
Halima Dawood

Abstract Background: Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135 000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. Methods: A decision analytic cost-effectiveness analysis and cost impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered five treatment arms: (a) standard of care; 2-week course of amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course of amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) (d) oral course; 2-week oral fluconazole/flucytosine (oral) and e) 1-week course amphotericin B/fluconazole (1wk AmBd/Flu). A sensitivity analysis was conducted on key variables. Results: The highest total treatment costs are in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, the 1-week AmBd/5FC, then standard of care with the lowest cost in the 1-week AmBd/Flu arm. Compared to standard of care the 1-week flucytosine course is most cost-effective at USD106/QALY. The cost impact analysis shows that the 1-week flucytosine course has an incremental cost of just over USD293 per patient per year compared to what is currently spent on standard of care Sensitivity analyses suggest that the model is most sensitive to the probability of survival at 12 months and hospital costs, particularly length of stay. Conclusions: The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective when it is used as a 1-week AmBd/5FC regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.


2021 ◽  
Vol 9 ◽  
Author(s):  
Stephen Okoboi ◽  
Barbara Castelnuovo ◽  
Jean-Pierre Van Geertruyden ◽  
Oucul Lazarus ◽  
Lung Vu ◽  
...  

Introduction: Distribution of HIV self-testing (HIVST) kits through MSM peer networks is a novel and effective strategy to increase HIV testing coverage in this high-risk population. No study has evaluated the cost or cost effectiveness of peer distribution of HIVST strategies among MSM in sub-Saharan Africa.Methods: From June to August 2018, we conducted a pilot study of secondary MSM peer HIVST kit distribution at The AIDS Support Organization at Entebbe and Masaka. We used an ingredients approach to estimate the cost of MSM peer HIVST kit distribution relative to standard-of-care (SOC) hotspot testing using programme expenditure data reported in US dollars. The provider perspective was used to estimate incremental cost-effective ratios per HIV infection averted using the difference in HIV annual transmission rates between MSM with HIV who knew their status and were not virologically suppressed and MSM with HIV who did not know their status.Results: We enrolled 297 participants of whom 150 received MSM peer HIVST kit distribution (intervention group) and 147 received TASO standard of care HIV testing (control group). Provider cost for the intervention was $2,276 compared with $1,827 for SOC during the 3-month study period. Overall, the intervention resulted in higher HIV positivity yield (4.9 vs. 1.4%) and averted more HIV infections per quarter (0.364 vs. 0.104) compared with SOC. The cost per person tested was higher for the intervention compared to SOC ($15.90 vs. $12.40). Importantly, the cost per new HIV diagnosis ($325 vs. $914) and cost per transmission averted ($6,253 vs. $ 17,567) were lower for the intervention approach relative to SOC. The incremental cost per HIV transmission averted by the self-testing program was $1,727. The incremental cost to providers per additional HIV-positive person identified by the intervention was $147.30.Conclusion: The intervention strategy was cost-effective, and identified more undiagnosed HIV infections than SOC hotspot testing at a cost-effectiveness threshold of US $2,129. Secondary distribution of HIVST kits through peers should further be evaluated with longer duration aimed at diagnosing 95% of all persons with HIV by 2030; the first UNAIDS 95-95-95 target.


2019 ◽  
Vol 69 (4) ◽  
pp. 588-595 ◽  
Author(s):  
Tao Chen ◽  
Lawrence Mwenge ◽  
Shabir Lakhi ◽  
Duncan Chanda ◽  
Peter Mwaba ◽  
...  

Abstract Background Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. Methods Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. Results Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91–1210) per life-year saved. Clinical Trials Registration ISRCTN45035509. Conclusions Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.


Author(s):  
James Buchanan ◽  
James Altunkaya ◽  
Nguyen Van Kinh ◽  
Nguyen Van Vinh Chau ◽  
Vo Trieu Ly ◽  
...  

Abstract Background Talaromycosis (penicilliosis) is an invasive fungal infection and a major cause of HIV-related deaths in Southeast Asia. Guidelines recommend induction therapy with amphotericin B deoxycholate, however treatment with itraconazole has fewer toxic effects, is easier to administer and is less expensive. Our recent randomized controlled trial in Vietnam found amphotericin B was superior to itraconazole with respect to six-month mortality. We undertook an economic evaluation alongside this trial to determine whether the more effective treatment is cost-effective. Methods Resource use, direct and indirect costs, health and quality of life outcomes (measured using quality-adjusted life-years; QALYs) were evaluated for 405 trial participants from 2012 to 2016. Both a Vietnamese health service and a broader societal costing perspective were considered. Mean costs and QALYs were combined to calculate the within-trial cost-effectiveness of amphotericin versus itraconazole from both perspectives. Results From a Vietnamese health service perspective, amphotericin increases costs but improves health outcomes compared to itraconazole, at a cost of $3,013/QALY gained. The probability that amphotericin is cost-effective at a conventional (WHO-CHOICE) threshold of value for money is 46%. From a societal perspective, amphotericin is cost-reducing and improves outcomes compared to itraconazole, and is likely to be a cost-effective strategy at any value for money threshold greater than $0. Conclusions Our analysis indicates that induction therapy with amphotericin is a cost-effective treatment strategy for HIV-infected adults diagnosed with talaromycosis in Vietnam. These results provide the evidence base for healthcare providers and policy makers to improve access to and use of amphotericin.


2018 ◽  
Author(s):  
Christian Selinger ◽  
Anna Bershteyn ◽  
Dobromir T. Dimitrov ◽  
Blythe J.S. Adamson ◽  
Paul Revill ◽  
...  

AbstractBackgroundRV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individualbased network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.MethodsConsistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.ResultsOur analysis shows that this partially effective vaccine could prevent, at catchup vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).ConclusionsWhile a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.


2019 ◽  
Vol 4 (2) ◽  
pp. 238146831987332 ◽  
Author(s):  
Christophe Sauboin ◽  
Laure-Anne Van Bellinghen ◽  
Nicolas Van De Velde ◽  
Ilse Van Vlaenderen

Background. Malaria is a major public health burden in sub-Saharan Africa. This study estimated the cost-effectiveness and budget impact of adding four-dose malaria vaccination in infants or children to existing interventions in 41 endemic countries in sub-Saharan Africa. Methods. A static Markov cohort model followed a simulated 2017 birth cohort (36.5 million children) for 15 years in 5-day cycles, comparing three strategies: child vaccination (doses at ages 6, 7.5, 9, and 27 months); infant vaccination (doses at ages 6, 10, and 14 weeks and 21 months); no malaria vaccination. The base-case analysis was conducted from the health system perspective with vaccine price assumed at USD5/dose and annual discounting of 3% for costs and disability-adjusted life-years (DALYs). Efficacy was based on the Phase III RTS,S clinical trial. Results. The model projected that 24.6 million children, or 26.2 million infants, would be vaccinated. Compared with no vaccination, child (infant) vaccination was projected to avert 16.8 million (16 million) cases of malaria and 113,000 (107,000) malaria deaths in the birth cohort over the 15-year period. The incremental cost-effectiveness ratio was USD200/DALY averted (USD225/DALY averted) for child (infant) vaccination, which represents 14% (17%) of the gross domestic product (GDP) per capita threshold. The estimated budget impact was overall larger for infant vaccination but mixed situations occurred across countries. Vaccine price, discount rate, and parasite prevalence had the largest effect on cost-effectiveness. Conclusions. Child vaccination with RTS,S would be more cost-effective than infant vaccination across countries. Adding RTS,S malaria vaccination to existing interventions would be cost-effective assuming one GDP per capita threshold for both child and infant vaccination in all examined countries except for 6 countries with lower transmission.


mBio ◽  
2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Joanne Livermore ◽  
Susan J. Howard ◽  
Andrew D. Sharp ◽  
Joanne Goodwin ◽  
Lea Gregson ◽  
...  

ABSTRACT Cryptococcal meningoencephalitis is an urgent global health problem. Induction regimens using 14 days of amphotericin B deoxycholate (dAmB) are considered the standard of care but may not be suitable for resource-poor settings. We investigated the efficacy of conventional and abbreviated regimens of dAmB for cryptococcal meningoencephalitis in both murine and rabbit models of cryptococcal meningoencephalitis. We examined the extent to which immunological effectors contribute to the antifungal effect. We bridged the results to humans as a first critical step to define regimens suitable for further study in clinical trials. There were significant differences in the murine plasma-versus-cerebrum dAmB concentration-time profiles. dAmB was detectable in the cerebrum throughout the experimental period, even following the administration of only three doses of 3 mg/kg. dAmB induced a fungistatic effect in the cerebrum with a 2- to 3-log10 CFU/g reduction compared with controls. The effect of 3 days of therapy was the same as that of daily therapy for 14 days. There was no evidence of increased numbers of CD3+ CD4+ or CD3+ CD8+ cells in treated mice to account for the persistent antifungal effect of an abbreviated regimen. The administration of dAmB at 1 mg/kg/day for 3 days was the same as daily therapy in rabbits. The bridging studies suggested that a human regimen of 0.7 mg/kg/day for 3 days resulted in nearly maximal antifungal activity in both the cerebrum and cerebrospinal fluid. An abbreviated regimen (3 days of therapy) of dAmB appears to be just as effective as conventional induction therapy for cryptococcal meningoencephalitis. IMPORTANCE Cryptococcal meningitis is a significant and neglected infection that is associated with excessive morbidity and mortality. In well-resourced health care settings, induction therapy with at least 2 weeks of amphotericin B deoxycholate (dAmB) is advocated. Multiple clinical studies suggest that dAmB is the drug of choice for cryptococcal meningitis. In many parts of the world where the burden of cryptococcal meningitis is highest, it is infeasible to administer dAmB for prolonged periods. This paper provides the experimental basis for the efficacy of abbreviated regimens of dAmB for cryptococcal meningitis. The concept was explored in two well-validated laboratory animal models of cryptococcal meningitis, and the results were bridged to humans by using a range of mathematical modeling techniques. A 3-day regimen is as effective as the standard 14-day course. An abbreviated regimen is significantly more feasible and may enable better antifungal therapy to be administered to many patients with this frequently lethal disease.


2019 ◽  
Vol 70 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Tinevimbo Shiri ◽  
Angela Loyse ◽  
Lawrence Mwenge ◽  
Tao Chen ◽  
Shabir Lakhi ◽  
...  

Abstract Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa.


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