Cost-effectiveness Of Antiretroviral Therapy Research Articles

Cost-Effectiveness of antiretroviral therapy: A systematic review.

The mobilization of resources to prevent and treat human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is unparalleled in the history of public health. The uptake of antiretroviral therapy (ART) has been rapid and unprecedented and made possible by the availability of funding - external and domestic. To justify continuous funding of ART in resource-scarce settings, a spate of cost-effectiveness studies has been undertaken in a number of countries. This paper is based on a systematic review of global studies on cost-effectiveness analysis of ART. The major objective was to review the existing literature on cost-effectiveness of ART to determine whether ART has been cost-effective (CE) in different settings. We searched PubMed and Google Scholar for articles published between 2008 and 2017. We included studies that measured costs as well as effectiveness of HIV treatment - specifically ART - using incremental cost-effectiveness ratio as one of the outcomes. We identified 15 studies that met the search criteria for inclusion in the systematic review. The review confirms that ART programs have been CE across different settings, contexts, and strategies. The review would be useful for countries that are straining to raise funds for the health sector, generally, and for AIDS prevention and control program, specifically. This would also be beneficial for carrying out similar studies, if necessary, and as an advocacy tool for garnering additional funding.

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy.

A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Risk of within-couple HIV transmission to the HIV-negative partner. Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

The cost-effectiveness of harm reduction

HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term.

Comparative effectiveness and cost-effectiveness of antiretroviral therapy and pre-exposure prophylaxis for HIV prevention in South Africa

BackgroundAntiretroviral therapy (ART) and oral pre-exposure prophylaxis (PrEP) are effective in reducing HIV transmission in heterosexual adults. The epidemiologic impact and cost-effectiveness of combined prevention approaches in resource-limited settings remain unclear.MethodsWe develop a dynamic mathematical model of the HIV epidemic in South Africa’s adult population. We assume ART reduces HIV transmission by 95% and PrEP by 60%. We model two ART strategies: scaling up access for those with CD4 counts ≤ 350 cells/μL (Guidelines) and for all identified HIV-infected individuals (Universal). PrEP strategies include use in the general population (General) and in high-risk individuals (Focused). We consider strategies where ART, PrEP, or both are scaled up to 100% of remaining eligible individuals yearly. We measure infections averted, quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratios over 20 years.ResultsScaling up ART to 50% of eligible individuals averts 1,513,000 infections over 20 years (Guidelines) and 3,591,000 infections (Universal). Universal ART is the most cost-effective strategy at any scale ($160-$220/QALY versus comparable scale Guidelines ART expansion). General PrEP is costly and provides limited benefits beyond ART scale-up ($7,680/QALY to add 100% PrEP to 50% Universal ART). Cost-effectiveness of General PrEP becomes less favorable when ART is widely given ($12,640/QALY gained when added to 100% Universal ART). If feasible, Focused PrEP is cost saving or highly cost effective versus status quo and when added to ART strategies.ConclusionsExpanded ART coverage to individuals in early disease stages may be more cost-effective than current guidelines. PrEP can be cost-saving if delivered to individuals at increased risk of infection.

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

BackgroundWe estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ).MethodsWe estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years.ResultsThe program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.Conclusions and SignificanceThe 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.

Evaluating the cost-effectiveness of combination antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Uganda

To model the cost-effectiveness in Uganda of combination antiretroviral therapy (ART) to prevent mother-to-child transmission of human immunodeficiency virus (HIV). The cost-effectiveness of ART was evaluated on the assumption that ART reduces the risk of an HIV-positive pregnant woman transmitting HIV to her baby from 40% (when the woman is left untreated) to 25.8%, 17.4% and 3.8%, respectively, when the woman is given: (i) single-dose nevirapine (at an estimated total drug cost of 0.06 United States dollars [US$]); (ii) dual therapy with zidovudine and lamivudine for 7 weeks (at a total drug cost of US$ 15.63); or (iii) ART for 18 months (at a total annual cost of US$ 469.77). Lifetime ART (US$ 6883), recommended for pregnant women with < 350 CD4+ T lymphocytes per mm(3), was assumed to give the same reduction in transmission risk in each subsequent pregnancy. Compared with single-dose nevirapine, dual therapy and no therapy, 18 months of ART averted 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs), respectively, at a cost of US$ 46, US$ 99 and US$ 34 per DALY averted. The corresponding figures for lifetime ART are, respectively, 19.20, 11.87 and 31.60 DALYs averted, at a cost of US$ 205, US$ 354 and US$ 172 per DALY averted. In Uganda, ART appears highly cost-effective for the prevention of mother-to-child HIV transmission, even if continued over the patients' lifetimes. Given the additional public health benefits of ART, efforts to ensure that all HIV-positive pregnant women have access to lifelong ART should be intensified.

Cost-Effectiveness of Antiretroviral Therapy for Prevention

Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy (ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raising issues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader with the conceptual tools and substantive background needed to understand and evaluate the policy and programmatic implications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start by introducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs, health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then review research on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIV prevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role of the acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectiveness analyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion of future directions for programmatic demonstrations and evaluation.

Cost-effectiveness of anti-retroviral therapy at a district hospital in southern Ethiopia

BackgroundAs the resource implications of expanding anti-retroviral therapy (ART) are likely to be large, there is a need to explore its cost-effectiveness. So far, there is no such information available from Ethiopia.ObjectiveTo assess the cost-effectiveness of ART for routine clinical practice in a district hospital setting in Ethiopia.MethodsWe estimated the unit cost of HIV-related care from the 2004/5 fiscal year expenditure of Arba Minch Hospital in southern Ethiopia. We estimated outpatient and inpatient service use from HIV-infected patients who received care and treatment at the hospital between January 2003 and March 2006. We measured the health effect as life years gained (LYG) for patients receiving ART compared with those not receiving such treatment. The study adopted a health care provider perspective and included both direct and overhead costs. We used Markov model to estimate the lifetime costs, health benefits and cost-effectiveness of ART.FindingsART yielded an undiscounted 9.4 years expected survival, and resulted in 7.1 extra LYG compared to patients not receiving ART. The lifetime incremental cost is US$2,215 and the undiscounted incremental cost per LYG is US$314. When discounted at 3%, the additional LYG decreases to 5.5 years and the incremental cost per LYG increases to US$325.ConclusionThe undiscounted and discounted incremental costs per LYG from introducing ART were less than the per capita GDP threshold at the base year. Thus, ART could be regarded as cost-effective in a district hospital setting in Ethiopia.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy

India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.

PIN36 MICROSIMULATION OR COHORT MODELING? A COMPARATIVE CASE STUDY IN HIV INFECTION

Background: A trade-off between validity and feasibility is inevitable in decision analytic modelling. In HIV infection, progression rates depend, inter alia, on individual case histories. Variability between individuals can conveniently be modelled using first-order Monte Carlo microsimulation. But this makes concurrent modelling of second-order uncertainty problematic, as probabilistic analysis is more readily applied to an aggregate cohort. Objective: The objectives of this study were to compare first-order Monte Carlo simulation to a cohort approach in modelling the cost-effectiveness of antiretroviral therapy (ART) in HIV infection, and to validate the two models against an existing published model (CEPAC). Methods: Two alternative Markov models were developed. Cost-effectiveness analyses (CEA) were performed with each model in which optimised background therapy (OBT) plus enfuvirtide was compared with OBT alone in treatment-experienced patients, from a US payer perspective using 2003 costs, discounting costs and effects at 3% per annum over a lifetime. Disease progression in both models was dependent on CD4 cell count, viral load set point, treatment, response, age, and opportunistic infections. The simulation model (ARAMIS) used tracker variables to accumulate individual case histories. Transition probabilities depended on this prognostic information and on elapsed time. The cohort model (CM) used more disease states than ARAMIS to model history and time dependency partially. Both models were populated with cohort data from the TORO-1 and TORO-2 trials; as distributions in ARAMIS and stratified according to disease states in the CM. Markov cycle lengths in ARAMIS and the CM were 1 and 3 months respectively. Results: Estimated mean total lifetime costs were as follows. For OBT, ARAMIS: $156,700; CM: $148,500 (CEPAC: $151,000), and for OBT + enfuvirtide ARAMIS: $201,600, CM: $180,100 (CEPAC: $205,900). Mean discounted quality adjusted life expectancy (in QALYs) for OBT was estimated as ARAMIS: 3.60; CM 3.64 (CEPAC: 3.78) and for OBT + enfuvirtide as ARAMIS:4.59 and CM: 4.29 (CEPAC: 4.58). Respective figures for undiscounted, unadjusted life expectancy (years) were ARAMIS: 4.90; CM: 4.77 (CEPAC: 4.64) for OBT and ARAMIS: 6.40; CM: 5.76 (CEPAC: 5.57) for OBT + enfuvirtide. Conclusions: For treatment-experienced patients, the new models generated comparable estimates of life expectancy and costs. These results were comparable to the current "gold standard" among models of ART. The cohort and simulation approaches have individual strengths and limitations. The cohort model minimises computing time and simplifies the incorporation of probabilistic analysis of uncertainty, an increasingly required feature. The microsimulation model allows a fuller set of model inputs and avoids over-simplifying assumptions, yet the use of individual case histories allows a more compact set of Markov states. Microsimulation may have greater face validity among clinicians, though technology assessors may see this as less important than probabilistic sensitivity analysis. Our results apply to relatively advanced disease and treatment-experienced patients.

The cost effectiveness of antiretroviral regimens for the treatment of HIV/AIDS.

To estimate survival, the number of life-years gained and cost effectiveness of antiretroviral therapy (ART) regimens, denoted as ERA-I [zidovudine + (didanosine or zalcitabine)]; ERA-II [stavudine + (didanosine or zalcitabine) or lamivudine + (zidovudine or didanosine or zalcitabine or stavudine)]; and ERA-III [2 nucleoside reverse transcriptase inhibitors + (1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor)]. Modelling of drug cost, cost of opportunistic diseases and survival of HIV positive men and women in the province of British Columbia who were first prescribed any ART between October 1992 and June 1996. A 'reference cohort' was modelled upon individuals in a longitudinal cohort of homosexual men followed since 1982. PERSPECTIVE AND SETTING: Third-party payer perspective in British Columbia, Canada. All HIV-positive men and women aged > or =18 years with CD4+ counts < or =350 cells/microL who were enrolled in the province-wide drug treatment programme. Annual costs, survival and cost-effectiveness ratios of successive ART regimens. Total costs [1997 Canadian dollars ($Can)] at 12 months under ERA-I, -II and -III were $Can4897, $Can6620 and $Can 11 914, respectively. Survival at 12 months under ERA-I, -II and -III was 89.6%, 91.0% and 97.6%, respectively. The annual incremental cost (estimated by the total incremental cost at 12 months) between ERA-II and ERA-I was $Can1723. The incremental cost-effectiveness ratios between ERA-III and ERA-I, and between ERA-III and ERA-II were $Can58 806 and $Can46 971 per life-year gained, respectively. We found the cost effectiveness of ERA-III ART regimens well within the range of currently funded therapies for the treatment of other chronic diseases.

Cost-effectiveness and cost-benefit in the prevention of mother-to-child transmission of HIV in developing countries

Approximately 25-30% of infants born to HIV-infected mothers in developing countries are infected with HIV. A range of approaches exists to reduce the rate of mother-to-child transmission (MCT). Currently however the only therapeutic approach proven to reduce such vertical transmission is the administration of zidovudine therapy during pregnancy delivery and the neonatal period in the absence of breast-feeding. The authors review economic evaluation as an approach to help guide the development of policies on preventing MCT in developing countries drawing from studies evaluating anti-retroviral therapy in sub-Saharan Africa and Thailand. Principles of economic evaluation are discussed followed by a review of available evidence and the consideration of the sensitivity of estimates to parameter variation the reliability of parameter estimates model completeness and comparability and affordability. Future evaluations of MCT interventions should include economic evaluation to determine whether the intervention if found to be effective can or should be implemented as a public health measure. Such economic evaluations should be clear and include a sensitivity analysis of the most important variables thought to influence effectiveness and costs. Affordability should also be considered and multiple outcome measures and frames of reference used.