Appl Health Econ Health Policy DOI 10.1007/s40258-014-0142-5
SYSTEMATIC REVIEW
A Systematic Review on Cost Effectiveness of HIV Prevention Interventions in the United States Ya-Lin A. Huang • Arielle Lasry • Angela B. Hutchinson • Stephanie L. Sansom
Ó Springer International Publishing Switzerland (outside the USA) 2014
Abstract Background The Centers for Disease Control and Prevention (CDC) focus on funding HIV prevention interventions likely to have high impact on the HIV epidemic. In its most recent funding announcement to state and local health department grantees, CDC required that health departments allocate the majority of funds to four HIV prevention interventions: HIV testing, prevention with HIV-positives and their partners, condom distribution and policy initiatives. Objective We conducted a systematic review of the published literature to determine the extent of the costeffectiveness evidence for each of those interventions. Methodology We searched for US-based studies published through October 2012. The studies that qualified for inclusion contained original analyses that reported costs per quality-adjusted life-year saved, life-year saved, HIV infection averted, or new HIV diagnosis. For each study, paired reviewers performed a detailed review and data extraction. We reported the number of studies related to each intervention and summarized key cost-effectiveness findings according to intervention type. Costs were converted to 2011 US dollars.
Electronic supplementary material The online version of this article (doi:10.1007/s40258-014-0142-5) contains supplementary material, which is available to authorized users. Y.-L. A. Huang (&) A. Lasry A. B. Hutchinson S. L. Sansom Division of HIV/AIDS Prevention, National Center for HIV/ AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop E-48, Atlanta, GA 30329, USA e-mail: [email protected]
Results Of the 50 articles that met the inclusion criteria, 33 related to HIV testing, 15 assessed prevention with HIVpositives and partners, three reported on condom distribution, and one reported on policy initiatives. Methodologies and cost-effectiveness metrics varied across studies and interventions, making them difficult to compare. Conclusion Our review provides an updated summary of the published evidence of cost effectiveness of four key HIV prevention interventions recommended by CDC. With the exception of testing-related interventions, including partner services, where economic evaluations suggest that testing often can be cost effective, more cost-effectiveness research is needed to help guide the most efficient use of HIV prevention funds.
Key Points for Decision Makers More cost-effectiveness evaluation research is needed in the US for interventions related to prevention for HIV positives, condom distribution, and policy initiatives. Cost-effectiveness estimates should be interpreted with caution given the heterogeneity in the methods used, the data describing costs and effectiveness, and the populations and settings to which the interventions were applied.
1 Introduction Federally funded HIV prevention programs in the US have prevented many HIV infections and associated medical
Y.-L. A. Huang et al.
costs [1]. Nonetheless, current incidence at about 50,000 new cases a year is predicted to increase HIV prevalence by 38 % over the next 10 years [2–4]. In response, the White House, in July 2010, released the National HIV/ AIDS Strategy (NHAS), the first comprehensive plan with clear priorities and goals for HIV prevention efforts, including a 25 % reduction in incidence by 2015 [5]. The Centers for Disease Control and Prevention (CDC) is the major federal funder of HIV prevention interventions through cooperative agreements with state and local health departments. In its most recent 5-year HIV prevention funding announcement to health departments, CDC included language requiring that at least 75 % of funds go to intervention types believed to have high impact on the HIV epidemic [6, 7]. Cost-effectiveness analyses assess the costs and outcomes of interventions and help inform decisions about resource allocation. The literature on the cost effectiveness of HIV prevention interventions has been growing. In anticipation of future needs, we built a database using a broad search strategy to collect published cost-effectiveness studies related to a comprehensive set of HIV interventions. The purpose of this study is to provide evidence for the cost effectiveness of the interventions recommended under the funding announcement and to highlight where more cost-effectiveness studies may be needed. Therefore, we limited our scope to the four interventions required under the health department funding announcement, including HIV testing, prevention with HIV-positives and their partners, condom distribution and efforts to align policies with optimal HIV prevention, care and treatment [6, 7]. We conducted a systematic review of the published cost-effectiveness evidence pertaining to those interventions and determined the extent of the evidence that supports each one. When possible, we compared costeffectiveness outcomes across the interventions.
2 Methodology 2.1 Literature Search and Acquisition We conducted a systematic search of six electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane, CINAHL, and EconLit for relevant studies published in English from the earliest date available in each database through October 2012. A broad search strategy was used with appropriate keywords and Medical Subject Heading (MeSH) terms that reflect two categories: (i) cost effectiveness and (ii) HIV prevention. The full electronic search strategy for each database is presented in the electronic supplementary material (ESM 1). In addition, we
conducted a manual search by cross-checking references of review articles obtained through the electronic search. 2.2 Inclusion/Exclusion Criteria We first screened all records retrieved from the electronic databases based on abstracts and titles to determine inclusion in the review. Studies were included if they contained original analyses; reported cost-utility (e.g., cost per quality-adjusted life-years saved) or cost-effectiveness outcomes (e.g., cost per life-years saved, cost per HIV infection averted, and cost per new HIV diagnosis); made assessments based on US data; and evaluated one of the four HIV intervention types required by the health department funding announcement: (1) HIV testing, (2) prevention with HIV-positives and their partners, (3) condom distribution and (4) policy initiatives [6, 7]. Policy initiatives were described in the funding announcement as efforts to align structures, policies, and regulations with optimal HIV prevention, care, and treatment and to improve efficiency of HIV prevention efforts. One example was to address structural barriers to routine opt-out testing. Intervention types were further divided into subcategories in the funding announcement. For HIV testing, subcategories were: (1a) routine testing of patients ages 13–64 in healthcare settings, (1b) targeted testing programs in nonhealthcare settings, (1c) routine early HIV screening for all pregnant women, and (1d) screening for other sexually transmitted diseases, hepatitis, and tuberculosis in conjunction with HIV testing. Targeted testing refers to testing based on behavioral, clinical, or demographic characteristics. For prevention with HIV-positives, subcategories were: (2a) linkage to care and treatment, retention in care, (2b) behavioral interventions and other risk-reduction services, (2c) interventions to prevent mother-to-child HIV transmission, and (2d) referral to other medical and social services. The funding announcement included partner services in (2b), the ‘‘behavioral interventions and other riskreduction services’’ subcategory. In this review, however, we created a unique subcategory for partner services to facilitate comparisons with other interventions aimed at increasing the number of new HIV diagnoses. We excluded published abstracts and studies that estimated the hypothetical intervention costs and effects that could result in an intervention being cost effective (i.e., threshold analyses). We also excluded studies related to HIV testing that focused on technologies used for early diagnosis of acute HIV infection, testing programs in healthcare settings targeting patients with HIV risk factors and comparisons of testing technologies because these fell outside of the primary focus of the CDC funding priorities. Additionally, we excluded evaluations of interventions that
Cost Effectiveness of CDC-Funded HIV Prevention Interventions
no longer reflect standard of care, in particular, zidovudine monotherapy for preventing perinatal HIV transmission. For each eligible article, two reviewers independently extracted detailed information using a pre-specified 29-item abstraction form (see ESM 2) on key aspects of each analysis, sources of data, and cost-effectiveness result. The reviewers discussed any discrepancies in their independent abstractions and reached a consensus. We adjusted costs to 2011 US dollars, using the medical care component of the Consumer Price Index [8]. For studies that did not provide the year of cost calculation, we applied the year of publication. In our main results, we summarized the cost-effectiveness ratios for each intervention type and subcategory. We reported as many of the four previously described costeffectiveness metrics as were described in each study. We reported the number of studies (n) and the number of costeffectiveness outcomes (k) within each study. When more than one study reported a cost-effectiveness ratio for an intervention, we reported the range of ratios reported. We did not report mean or median of ratios because intervention implemented and methodologies used varied widely even under the same intervention type. We stratified costeffectiveness outcomes by the HIV prevalence (\1 %, 1–5 %, [5 %) of the population receiving the intervention when applicable.
3 Results Our comprehensive search yielded 4,633 records. We rejected 4,571 studies based on our inclusion criteria. Sixty-two articles were selected for full text review and upon review we excluded a further 12 (see ESM 3). We identified a total of 50 distinct studies as relevant and thus included them in the primary review (Fig. 1). We provide detailed information about each study in the electronic supplementary material (see ESM 4 Table), including individual cost-effectiveness ratios by intervention type, comparator strategy (including none), target population, types of costs included, settings, perspective, and analytic horizon. The year of publication for the included cost-effectiveness studies ranged from 1991 to 2012, with the majority published after 2000. We classified the 50 distinct studies under the four main intervention types: 33 studies related to HIV testing, 15 studies assessed prevention for HIV-positives, three reported on condom distribution and one reported on policy initiatives. Four studies evaluated multiple interventions or intervention subcategories, so the number of interventions evaluated exceeded the number of publications. The HIV testing studies were further classified as routine HIV screening in healthcare settings (22 of
Published articles and reports written in English identified through electronic databases and manual search (n=4,633)
Articles screened on basis of title and abstract
Out-of-scope (n=4,571): No cost-utility or cost-effectiveness outcomes reported (n=3,801) Review articles (n=127) Not US-based data (n=344) Interventions not of interest (n=299)
Included (n=62)
Full text review and application of exclusion criteria
Excluded (n=12)
Final studies included for primary review (n=50)
Fig. 1 Flow diagram of study selection
33), testing aimed at populations at higher risk of HIV infection in non-healthcare settings (7 of 33), early HIV screening of pregnant women (5 of 33), and screening for other diseases in conjunction with HIV (1 of 33). Under prevention for HIV-positives, the majority of studies evaluated partner services (9 of 15); two studies were identified for behavior interventions and for intervention to prevent mother-to-child HIV transmission; and only one study was identified for linkage to care and for referral to other medical and social services. The study of policy initiatives assessed the cost effectiveness of one law to deregulate access to syringes and one to increase alcohol taxes (Table 1). Of the 22 studies related to routine testing in healthcare settings, the most common setting evaluated was emergency departments and urgent care centers (9 studies). Other studies were conducted in hospital or primary care settings, STD clinics, the Veterans Administration, or did not specify the setting. Most of the studies found that it was cost effective (if compared to a US$100,000 per QALY threshold) or cost saving to routinely test for HIV in healthcare settings. Cost effectiveness ranged widely with HIV prevalence and it was more cost effective when the intervention was implemented for the population with a higher prevalence level (ESM 4). Methods used in the studies to determine outcomes varied. More than two-thirds employed mathematical
k
Range
n
Range
n
k
Cost per LY saved
Cost per QALY saved
5
1
1–5 % Prevalence
[5 % Prevalence 2
18
18 $23,000–$23,900
$19,500–$242,100
Cost saving–$1,854,600 –
2
3
1
[5 % Prevalence 3
2 2 $11,900–$70,200
$64,300–$66,500 Cost saving–$499,100 1
– –
–
1–5 % Prevalence
[5 % Prevalence
– –
–
– –
–
2 –
– –
– –
–
Cost saving–$15,200
$10,000–$28,200
2 3
– –
–
$16,700–$114,000
$10,500–$101,500
– –
–
6
7
–
–
–
–
–
–
1
$66,300
–
–
–
–
– –
– –
– –
– –
– – –
–
1
Cost saving
1
$77,400
1
[5 % Prevalence –
Cost saving
1 –
Cost saving
1
–
–
–
–
1
–
–
–
–
2
–
–
–
–
Cost saving–$2,800
– –
–
–
n number of studies, k number of cost-effectiveness outcomes, QALY quality-adjusted life years, LY life years
Multiple outcomes may be generated from one study
–
(4) Policy initiatives (n = 1) [11]
1
1–5 % Prevalence
(3) Condom distribution (n = 3) [10, 11, 70]
1
(2d) Referral to other medical and social services (n = 1) [69]
1
(2c) Intervention to prevent mother-to-child HIV transmission (n = 2) [67, 68]
1–5 % Prevalence [5 % Prevalence
(2b-1) Partner services (n = 9) [45, 59–66]
–
(2b) Behavior interventions and other risk-reduction services (n = 2) [57, 58]
1
(2a) Linkage to care and treatment, and interventions to improve retention in care (n = 1) [56]
(2) Prevention with HIV-positive individuals (n = 15)
\1 % Prevalence
(1d) Screening for other STD, hepatitis, and tuberculosis in conjunction with HIV testing (n = 1) [24]
–
–
\1 % Prevalence
(1c) Routine, early HIV screening for all pregnant women (n = 5) [51–55]
1 1
\1 % Prevalence 1–5 % Prevalence
(1b) Targeted testing programs in non-healthcare settings (n = 7) [44–50]
8
\1 % Prevalence
(1a) Routine testing of patients ages 13–64 in healthcare settings (n = 22) [14, 24–44]
(1) HIV testing (n = 33)
Intervention
Table 1 Summary of cost-effectiveness studies and outcomes by intervention (in US dollars)
1
–
2
–
1
1 –
2
–
2
–
2
–
2
3 –
3
–
–
–
– –
3
5
–
– –
–
–
4
k
2
4
–
– –
–
–
2
n
$6,000–$7,000
–
$31,000–$38,600
–
Cost saving–$186,300
$53,300–$54,500 –
$107,700–$535,800
–
–
–
Cost saving–cost saving
$53,500–$333,900
–
– –
–
–
$43,200–$348,000
Range
Cost per HIV infection averted
–
–
–
–
–
4 6
–
–
1
–
–
–
1
2 3
1
6
4
n
6
–
–
–
–
–
5 9
–
–
1
–
–
–
2
4 4
3
13
k
–
–
–
–
–
$3,100–$13,800 $3,200–$25,400
–
–
$11,800
–
–
–
$4,100–$9,400
$4,200–$31,300 $3,000–$21,000
$4,900–$7,500
$2,000–$30,500
$2,700–$13,500
Range
Cost per new HIV diagnosis
Y.-L. A. Huang et al.
Cost Effectiveness of CDC-Funded HIV Prevention Interventions
simulation models to estimate economic and epidemiological outcomes, rather than rely solely on empirical data. Due to the personal mode and relatively low rate of HIV transmission, models are often required for cost-effectiveness evaluation to translate intermediate outcomes relating services rendered, persons reached or condom usage into final outcomes or infections averted. In terms of costs, most studies assessed variable costs only (e.g., labor costs, cost of testing kits); less than 30 % included fixed costs (e.g., overheads, start-up costs). The majority of the studies did not conduct primary cost data collection, but instead estimated costs from other publications (ESM 4). We summarized the individual cost-effectiveness ratios and, when possible, ranges of ratios, across interventions and cost-effectiveness metrics (Table 1). Often only one study with one outcome was available for an intervention, and in many other cases, three or fewer studies were available. Studies reporting negative cost-effectiveness values were noted as cost saving. Cost per HIV infection averted was reported for at least one subcategory of each of the four key intervention types. The cost per new HIV diagnosis was reported for three of the four subcategories under HIV testing, as well as for the partner services subcategory. Overall, the outcomes of this metric fell in similar ranges across the subcategories. At the low prevalence level (\1 %), the cost of detecting a new HIV case fell within a smaller range for routine testing in healthcare settings (range = US$2,700–US$13,500, n = 4) than for targeted testing in non-healthcare settings (range = US$4,200–US$31,300, n = 2).
4 Discussion Our objective was to identify the extent to which the existing cost-effectiveness literature addressed the four key HIV prevention interventions required in the recent CDC HIV prevention funding announcement to health departments: HIV testing, prevention for HIV-positives, condom distribution, and policy initiatives. Of these prevention interventions, there is a growing body of literature on the cost effectiveness of HIV testing, particularly routine testing in healthcare settings. Forty-four percent (22 out of 50) of the studies included in our review were classified under that subcategory. The majority (14 out of 22) of those studies were published after 2006, following the issuance of CDC’s 2006 testing recommendation regarding routine HIV testing for all persons aged 13–64 years in healthcare settings [9]. Nearly one-fifth (9 out of 50) of the cost-effectiveness studies included in our review were classified under the partner services subcategory, with many of those published prior to 2000. Fewer than half of the studies included in our review belonged to the
remaining nine intervention subcategories, indicating paucity of cost-effectiveness evaluations related to prevention for HIV-positives, condom distribution, and policy initiatives. A number of reasons may explain the lack of economic evaluations for some interventions relative to others. Policy initiatives are difficult to evaluate with respect to costs and effectiveness. In regard to the latter, the effects of policy initiatives on changes in HIV transmission and acquisition also are difficult to quantify. The cost of condom distribution may be more readily estimated [10, 11], but assessing its effects requires detailed knowledge of the size of the associated increases in condom use, as well as of the risk factors among those who began using condoms more often or increased their use. Evaluating the efficacy of behavioral interventions for people living with HIV requires a reliance on self-reported risk behaviors before and after the delivery of an intervention and some studies are limited in follow-up periods to assess the duration of those effects. Assessing the costs of testing, including that associated with partner services, is relatively straightforward, as is documenting the number of new diagnoses associated with testing. The effects of a new diagnosis on enhanced life expectancy and reduced transmission, though more challenging, can be calculated based on empirical data on the likelihood of behavioral risk reduction and receipt of treatment, and the modeling of subsequent disease progression and transmission [12–14]. The diversity in methodology, assumptions, and models used to estimate the cost-effectiveness outcomes across studies and interventions makes it difficult to evaluate quality. Therefore, we did not attempt to assess the quality of the methods used to estimate costs or effectiveness. Standardization of model types and input data assumptions for translating intermediate outcomes into final outcomes would be helpful to generate comparable quality and outcomes across studies. In addition, though we reported individual cost-effectiveness ratios and ranges of ratios across similar interventions, these estimates should be interpreted with caution given the heterogeneity in the economic evaluation methods used, the data describing costs and effectiveness, and the populations and settings to which the interventions were applied. As one example, some of the included cost-effectiveness analyses were conducted in medium- or high-prevalence populations and settings, and therefore are not generalizable to low-prevalence settings. Moreover, the value of a certain type of intervention is likely underestimated if it is measured solely based on the number of HIV infections averted. One example is linkage to care and treatment, and interventions to improve retention, in which one of their major goals is to improve the health status and quality of life of infected persons, in addition to preventing new infections. Last, as
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is the case with all reviews of published studies, our findings may also be subject to publication selection bias. In spite of the heterogeneity among studies, this descriptive assessment is helpful in supporting policymakers or those charged with HIV resource allocation decisions in several ways. First, it identifies the body of evidence of cost effectiveness for the various interventions considered. And, where lacking, this review encourages decision-makers to seek local data on the costs and outcomes of HIV programs. These data could then be used to map out an evidenced-based HIV intervention portfolio. Funding decisions are typically influenced by a myriad of factors including historical spending, epidemic data, stakeholder pressures and other non-quantifiable factors; with this study, we expect to further inform this decisionmaking process. Our cost-effectiveness findings include interventions specified in CDC’s health department funding announcement for HIV prevention, and do not represent the full costeffectiveness literature on HIV prevention. For instance, there is a growing body of literature on the cost effectiveness of diagnosing acute and early HIV infection [13, 15, 16]. These studies generally support using highly sensitive HIV testing technologies to enable early identification of infection and eliminate onward transmission of acute HIV infection in high-incidence settings. Also not included were studies that evaluated late-stage perinatal testing which is also supported by cost-effectiveness evidence [17]. Additionally, we did not evaluate intervention strategies that have been shown to be promising in recent model-based studies, such as pre-exposure prophylaxis [16, 18–20] and treatment as prevention [21–23]. In summary, our analysis highlights the extent to which the published cost-effectiveness literature supports four key HIV prevention interventions recommended by CDC, and suggests areas where evaluations are limited. With the exception of HIV testing-related interventions, including partner services, where economic evaluations suggest that testing is cost effective in most cases, more cost-effectiveness research is needed to fill the knowledge gaps of interventions related to prevention for HIV-positives, condom distribution, and policy initiatives, in order to help guide the most efficient use of resources. Acknowledgments We sincerely thank Christy Cechman and Barbara Landreth for their help on our literature search. We also thank Paul Farnham, Ram Shrestha, Feng Lin, Chaitra Gopalappa, Robert Koppenhaver, Stephen Sorenson, Steve Nesheim, and Allan Taylor for their help in reviewing and abstracting studies. Funding and conflict of interest The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. No sources of funding were used to conduct this study or to prepare this
manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review. Author contributions Conception and design: YLH, AL, SLS; data collection: YLH, AL; analysis and interpretation: YLH, AL, AH, SLS; writing the article: YLH; critical revision of the article: AL, AH, SLS; overall responsibility: YLH.
References 1. Farnham PG, Holtgrave DR, Sansom SL, Hall HI. Medical costs averted by HIV prevention efforts in the United States, 1991–2006. J Acquir Immune Defic Syndr. 2010;54(5):565–7. 2. Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520–9. 3. Prejean J, Song R, Hernandez A, Ziebell R, Green T, Walker F, et al. Estimated HIV incidence in the United States, 2006–2009. PloS One. 2011;6(8):e17502. 4. Hall HI, Green TA, Wolitski RJ, Holtgrave DR, Rhodes P, Lehman JS, et al. Estimated future HIV prevalence, incidence, and potential infections averted in the United States: a multiple scenario analysis. J Acquir Immune Defic Syndr. 2010;55(2): 271–6. 5. National HIV/AIDS Strategy for the United States. Office of National AIDS Policy; 2010. 6. CDC. Funding Opportunity Announcement (FOA) PS12-1201: Comprehensive HIV Prevention Programs for Health Departments [cited 8/15/2012]. Available from: http://www.cdc.gov/ hiv/topics/funding/PS12-1201/. 7. CDC. CDC’S New High-Impact Approach to HIV Prevention Funding for Health Departments. Advancing the National HIV/ AIDS Strategy [cited 5/11/2012]. Available from: http://www. cdc.gov/hiv/topics/funding/PS12-1201/resources/factsheet/pdf/ foa-partner.pdf. 8. Bureau of Labor Statistics. Medical Care Consumer Price Index [cited]. Available from: http://data.bls.gov/cgi-bin/survey most?cu. 9. Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1–17. 10. Bedimo AL, Pinkerton SD, Cohen DA, Gray B, Farley TA. Condom distribution: a cost-utility analysis. Int J STD AIDS. 2002;13(6):384–92. 11. Cohen DA, Wu SY, Farley TA. Structural interventions to prevent HIV/sexually transmitted disease: are they cost-effective for women in the southern United States? Sex Transm Dis. 2006;33(7 Suppl):S46–9. 12. Prabhu VS, Hutchinson AB, Farnham PG, Sansom SL. Sexually acquired HIV infections in the United States due to acute-phase HIV transmission: an update. AIDS. 2009;23(13):1792–4. 13. Hutchinson AB, Patel P, Sansom SL, Farnham PG, Sullivan TJ, Bennett B, et al. Cost-effectiveness of pooled nucleic acid amplification testing for acute HIV infection after third-generation HIV antibody screening and rapid testing in the United States: a comparison of three public health settings. PLoS Med. 2010;7(9):e1000342. 14. Farnham PG, Sansom SL, Hutchinson AB. How much should we pay for a new HIV diagnosis? A mathematical model of HIV screening in US clinical settings. Med Decis Making. 2012;32(3):459–69.
Cost Effectiveness of CDC-Funded HIV Prevention Interventions 15. Long EF. HIV screening via fourth-generation immunoassay or nucleic acid amplification test in the United States: a costeffectiveness analysis. PloS One. 2011;6(11):16. 16. Juusola JL, Brandeau ML, Long EF, Owens DK, Bendavid E. The cost-effectiveness of symptom-based testing and routine screening for acute HIV infection in men who have sex with men in the USA. AIDS. 2011;25(14):1779–87. 17. Sansom SL, Jamieson DJ, Farnham PG, Bulterys M, Fowler MG. Human immunodeficiency virus retesting during pregnancy: costs and effectiveness in preventing perinatal transmission. Obstet Gynecol. 2003;102(4):782–90. 18. Desai K, Sansom SL, Ackers ML, Stewart SR, Hall HI, Hu DJ, et al. Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness. AIDS. 2008;22(14): 1829–39. 19. Paltiel AD, Freedberg KA, Scott CA, Schackman BR, Losina E, Wang B, et al. HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and costeffectiveness. Clin Infect Dis. 2009;48(6):806–15. 20. Koppenhaver RT, Sorensen SW, Farnham PG, Sansom SL. The cost-effectiveness of pre-exposure prophylaxis in men who have sex with men in the United States: an epidemic model. J Acquir Immune Defic Syndr. 2011;58(2):e51–2. 21. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373(9657):48–57. 22. Walensky RP, Ross EL, Kumarasamy N, Wood R, Noubary F, Paltiel AD, et al. The cost-effectiveness of treatment as prevention: analysis of the HPTN 052 trial. International AIDS Conference. Washington DC, US; 2012. 23. Granich R, Kahn JG, Bennett R, Holmes CB, Garg N, Serenata C, et al. Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011–2050. PLoS One. 2012;7(2):e30216. 24. Silva A, Glick NR, Lyss SB, Hutchinson AB, Gift TL, Pealer LN, et al. Implementing an HIV and sexually transmitted disease screening program in an emergency department. Ann Emerg Med. 2007;49(5):564–72. 25. Lurie P, Avins AL, Phillips KA, Kahn JG, Lowe RA, Ciccarone D. The cost-effectiveness of voluntary counseling and testing of hospital inpatients for HIV infection. JAMA. 1994;272(23): 1832–8. 26. Owens DK, Nease RF Jr, Harris RA. Cost-effectiveness of HIV screening in acute care settings. Arch Intern Med. 1996;156(4): 394–404. 27. Phillips KA, Fernyak S. The cost-effectiveness of expanded HIV counselling and testing in primary care settings: a first look. AIDS. 2000;14(14):2159–69. 28. Walensky RP, Weinstein MC, Kimmel AD, Seage GR 3rd, Losina E, Sax PE, et al. Routine human immunodeficiency virus testing: an economic evaluation of current guidelines. Am J Med. 2005;118(3):292–300. 29. Walensky RP, Losina E, Malatesta L, Barton GE, O’Connor CA, Skolnik PR, et al. Effective HIV case identification through routine HIV screening at urgent care centers in Massachusetts. Am J Public Health. 2005;95(1):71–3. 30. Sanders GD, Bayoumi AM, Sundaram V, Bilir SP, Neukermans CP, Rydzak CE, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med. 2005;352(6):570–85. 31. Paltiel AD, Weinstein MC, Kimmel AD, Seage GR 3rd, Losina E, Zhang H, et al. Expanded screening for HIV in the United States—an analysis of cost-effectiveness. N Engl J Med. 2005;352(6):586–95.
32. Paltiel AD, Walensky RP, Schackman BR, Seage GR 3rd, Mercincavage LM, Weinstein MC, et al. Expanded HIV screening in the United States: effect on clinical outcomes, HIV transmission, and costs. Ann Intern Med. 2006;145(11):797–806. 33. Holtgrave DR. Costs and consequences of the US Centers for Disease Control and Prevention’s recommendations for opt-out HIV testing. PLoS Med. 2007;4(6):e194. 34. Brown J, Shesser R, Simon G, Bahn M, Czarnogorski M, Kuo I, et al. Routine HIV screening in the emergency department using the new US Centers for Disease Control and Prevention Guidelines: results from a high-prevalence area. J Acquir Immune Defic Syndr. 2007;46(4):395–401. 35. Farnham PG, Hutchinson AB, Sansom SL, Branson BM. Comparing the costs of HIV screening strategies and technologies in health-care settings. Public Health Rep. 2008;123(Suppl 3):51–62. 36. Sanders GD, Bayoumi AM, Holodniy M, Owens DK. Costeffectiveness of HIV screening in patients older than 55 years of age. Ann Intern Med. 2008;148(12):889–903. 37. Long EF, Brandeau ML, Owens DK. The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Ann Intern Med. 2010;153(12):778–89. 38. Sanders GD, Anaya HD, Asch S, Hoang T, Golden JF, Bayoumi AM, et al. Cost-effectiveness of strategies to improve HIV testing and receipt of results: economic analysis of a randomized controlled trial. J Gen Intern Med. 2010;25(6):556–63. 39. Torres GW, Heffelfinger JD, Pollack HA, Barrera SG, Rothman RE. HIV screening programs in US emergency departments: a cross-site comparison of structure, process, and outcomes. Ann Emerg Med. 2011;58(1 Suppl 1):S104–13. 40. Hsieh YH, Jung JJ, Shahan JB, Pollack HA, Hairston HS, Moring-Parris D, et al. Outcomes and cost analysis of 3 operational models for rapid HIV testing services in an academic inner-city emergency department. Ann Emerg Med. 2011;58(1 Suppl 1):S133–9. 41. Hutchinson AB, Farnham PG, Lyss SB, White DA, Sansom SL, Branson BM. Emergency department HIV screening with rapid tests: a cost comparison of alternative models. AIDS Educ Prev. 2011;23(3 Suppl):58–69. 42. Prabhu VS, Farnham PG, Hutchinson AB, Soorapanth S, Heffelfinger JD, Golden MR, et al. Cost-effectiveness of HIV screening in STD clinics, emergency departments, and inpatient units: a model-based analysis. PLoS One. 2011;6(5):e19936. 43. Walensky RP, Morris BL, Reichmann WM, Paltiel AD, Arbelaez C, Donnell-Fink L, et al. Resource utilization and cost-effectiveness of counselor- vs. provider-based rapid point-of-care HIV screening in the emergency department. PLoS One. 2011;6(10):12. 44. Shrestha RK, Clark HA, Sansom SL, Song B, Buckendahl H, Calhoun CB, et al. Cost-effectiveness of finding new HIV diagnoses using rapid HIV testing in community-based organizations. Public Health Rep. 2008;123(Suppl 3):94–100. 45. Golden MR, Gift TL, Brewer DD, Fleming M, Hogben M, St Lawrence JS, et al. Peer referral for HIV case-finding among men who have sex with men. AIDS. 2006;20(15):1961–8. 46. Varghese B, Peterman TA. Cost-effectiveness of HIV counseling and testing in US prisons. J Urban Health. 2001;78(2):304–12. 47. Shrestha RK, Sansom SL, Richardson-Moore A, French PT, Scalco B, Lalota M, et al. Costs of voluntary rapid HIV testing and counseling in jails in 4 states—advancing HIV Prevention Demonstration Project, 2003–2006. Sex Transm Dis. 2009;36(2 Suppl):S5–8. 48. Shrestha RK, Sansom SL, Schulden JD, Song B, Smith LC, Ramirez R, et al. Costs and effectiveness of finding new HIV diagnoses by using rapid testing in transgender communities. AIDS Educ Prev. 2011;23(3 Suppl):49–57.
Y.-L. A. Huang et al. 49. Schackman BR, Metsch LR, Colfax GN, Leff JA, Wong A, Scott CA, et al. The cost-effectiveness of rapid HIV testing in substance abuse treatment: results of a randomized trial. Drug Alcohol Depend. 2012;6:6. 50. Cipriano LE, Zaric GS, Holodniy M, Bendavid E, Owens DK, Brandeau ML. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users. PLoS One. 2012;7(9):18. 51. Grobman WA, Garcia PM. The cost-effectiveness of voluntary intrapartum rapid human immunodeficiency virus testing for women without adequate prenatal care. Am J Obstet Gynecol. 1999;181(5 Pt 1):1062–71. 52. Immergluck LC, Cull WL, Schwartz A, Elstein AS. Cost-effectiveness of universal compared with voluntary screening for human immunodeficiency virus among pregnant women in Chicago. Pediatrics. 2000;105(4):E54. 53. Zaric GS, Bayoumi AM, Brandeau ML, Owens DK. The cost effectiveness of voluntary prenatal and routine newborn HIV screening in the United States. J Acquir Immune Defic Syndr. 2000;25(5):403–16. 54. Resch S, Altice FL, Paltiel AD. Cost-effectiveness of HIV screening for incarcerated pregnant women. J Acquir Immune Defic Syndr. 2005;38(2):163–73. 55. Myers ER, Thompson JW, Simpson K. Cost-effectiveness of mandatory compared with voluntary screening for human immunodeficiency virus in pregnancy. Obstet Gynecol. 1998;91(2): 174–81. 56. Gopalappa C, Farnham PG, Hutchinson AB, Sansom SL. Cost effectiveness of the National HIV/AIDS Strategy goal of increasing linkage to care for HIV-infected persons. J Acquir Immune Defic Syndr. 2012;61(1):99–105. 57. Lee MB, Leibowitz A, Rotheram-Borus MJ. Cost-effectiveness of a behavioral intervention for seropositive youth. AIDS Educ Prev. 2005;17(2):105–18. 58. Marseille E, Shade SB, Myers J, Morin S. The cost-effectiveness of HIV prevention interventions for HIV-infected patients seen in clinical settings. J Acquir Immune Defic Syndr. 2011;56(3): e87–94. 59. Rutherford GW, Woo JM, Neal DP, Rauch KJ, Geoghegan C, McKinney KC, et al. Partner notification and the control of human immunodeficiency virus infection. Two years of experience in San Francisco. Sex Transm Dis. 1991;18(2):107–10.
60. Pavia AT, Benyo M, Niler L, Risk I. Partner notification for control of HIV: results after 2 years of a statewide program in Utah. Am J Public Health. 1993;83(10):1418–24. 61. Spencer NE, Hoffman RE, Raevsky CA, Wolf FC, Vernon TM. Partner notification for human immunodeficiency virus infection in Colorado: results across index case groups and costs. Int J STD AIDS. 1993;4(1):26–32. 62. Toomey KE, Peterman TA, Dicker LW, Zaidi AA, Wroten JE, Carolina J. Human immunodeficiency virus partner notification. Cost and effectiveness data from an attempted randomized controlled trial. Sex Transm Dis. 1998;25(6):310–6. 63. Varghese B, Peterman TA, Holtgrave DR. Cost-effectiveness of counseling and testing and partner notification: a decision analysis. AIDS. 1999;13(13):1745–51. 64. Ahrens K, Kent CK, Kohn RP, Nieri G, Reynolds A, Philip S, et al. HIV partner notification outcomes for HIV-infected patients by duration of infection, San Francisco, 2004–2006. J Acquir Immune Defic Syndr. 2007;46(4):479–84. 65. Shrestha RK, Begley EB, Hutchinson AB, Sansom SL, Song B, Voorhees K, et al. Costs and effectiveness of partner counseling and referral services with rapid testing for HIV in Colorado and Louisiana, United States. Sex Transm Dis. 2009;36(10):637–41. 66. Shrestha RK, Sansom SL, Kimbrough L, Hutchinson AB, Daltry D, Maldonado W, et al. Cost-effectiveness of using social networks to identify undiagnosed HIV infection among minority populations. J Public Health Manag Pract. 2010;16(5):457–64. 67. Halpern MT, Read JS, Ganoczy DA, Harris DR. Cost-effectiveness of cesarean section delivery to prevent mother-to-child transmission of HIV-1. AIDS. 2000;14(6):691–700. 68. Mrus JM, Goldie SJ, Weinstein MC, Tsevat J. The cost-effectiveness of elective Cesarean delivery for HIV-infected women with detectable HIV RNA during pregnancy. AIDS. 2000;14(16):2543–52. 69. Holtgrave DR, Wolitski RJ, Pals SL, Aidala A, Kidder DP, Vos D, et al. Cost-utility analysis of the housing and health intervention for homeless and unstably housed persons living with HIV. AIDS Behav. 2012;16:16. 70. Holtgrave DR, Maulsby C, Kharfen M, Jia Y, Wu C, Opoku J, et al. Cost-utility analysis of a female condom promotion program in Washington,DC. AIDS Behav. 2012;16(5):1115–20.
SYSTEMATIC REVIEW
A Systematic Review on Cost Effectiveness of HIV Prevention Interventions in the United States Ya-Lin A. Huang • Arielle Lasry • Angela B. Hutchinson • Stephanie L. Sansom
Ó Springer International Publishing Switzerland (outside the USA) 2014
Abstract Background The Centers for Disease Control and Prevention (CDC) focus on funding HIV prevention interventions likely to have high impact on the HIV epidemic. In its most recent funding announcement to state and local health department grantees, CDC required that health departments allocate the majority of funds to four HIV prevention interventions: HIV testing, prevention with HIV-positives and their partners, condom distribution and policy initiatives. Objective We conducted a systematic review of the published literature to determine the extent of the costeffectiveness evidence for each of those interventions. Methodology We searched for US-based studies published through October 2012. The studies that qualified for inclusion contained original analyses that reported costs per quality-adjusted life-year saved, life-year saved, HIV infection averted, or new HIV diagnosis. For each study, paired reviewers performed a detailed review and data extraction. We reported the number of studies related to each intervention and summarized key cost-effectiveness findings according to intervention type. Costs were converted to 2011 US dollars.
Electronic supplementary material The online version of this article (doi:10.1007/s40258-014-0142-5) contains supplementary material, which is available to authorized users. Y.-L. A. Huang (&) A. Lasry A. B. Hutchinson S. L. Sansom Division of HIV/AIDS Prevention, National Center for HIV/ AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop E-48, Atlanta, GA 30329, USA e-mail: [email protected]
Results Of the 50 articles that met the inclusion criteria, 33 related to HIV testing, 15 assessed prevention with HIVpositives and partners, three reported on condom distribution, and one reported on policy initiatives. Methodologies and cost-effectiveness metrics varied across studies and interventions, making them difficult to compare. Conclusion Our review provides an updated summary of the published evidence of cost effectiveness of four key HIV prevention interventions recommended by CDC. With the exception of testing-related interventions, including partner services, where economic evaluations suggest that testing often can be cost effective, more cost-effectiveness research is needed to help guide the most efficient use of HIV prevention funds.
Key Points for Decision Makers More cost-effectiveness evaluation research is needed in the US for interventions related to prevention for HIV positives, condom distribution, and policy initiatives. Cost-effectiveness estimates should be interpreted with caution given the heterogeneity in the methods used, the data describing costs and effectiveness, and the populations and settings to which the interventions were applied.
1 Introduction Federally funded HIV prevention programs in the US have prevented many HIV infections and associated medical
Y.-L. A. Huang et al.
costs [1]. Nonetheless, current incidence at about 50,000 new cases a year is predicted to increase HIV prevalence by 38 % over the next 10 years [2–4]. In response, the White House, in July 2010, released the National HIV/ AIDS Strategy (NHAS), the first comprehensive plan with clear priorities and goals for HIV prevention efforts, including a 25 % reduction in incidence by 2015 [5]. The Centers for Disease Control and Prevention (CDC) is the major federal funder of HIV prevention interventions through cooperative agreements with state and local health departments. In its most recent 5-year HIV prevention funding announcement to health departments, CDC included language requiring that at least 75 % of funds go to intervention types believed to have high impact on the HIV epidemic [6, 7]. Cost-effectiveness analyses assess the costs and outcomes of interventions and help inform decisions about resource allocation. The literature on the cost effectiveness of HIV prevention interventions has been growing. In anticipation of future needs, we built a database using a broad search strategy to collect published cost-effectiveness studies related to a comprehensive set of HIV interventions. The purpose of this study is to provide evidence for the cost effectiveness of the interventions recommended under the funding announcement and to highlight where more cost-effectiveness studies may be needed. Therefore, we limited our scope to the four interventions required under the health department funding announcement, including HIV testing, prevention with HIV-positives and their partners, condom distribution and efforts to align policies with optimal HIV prevention, care and treatment [6, 7]. We conducted a systematic review of the published cost-effectiveness evidence pertaining to those interventions and determined the extent of the evidence that supports each one. When possible, we compared costeffectiveness outcomes across the interventions.
2 Methodology 2.1 Literature Search and Acquisition We conducted a systematic search of six electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane, CINAHL, and EconLit for relevant studies published in English from the earliest date available in each database through October 2012. A broad search strategy was used with appropriate keywords and Medical Subject Heading (MeSH) terms that reflect two categories: (i) cost effectiveness and (ii) HIV prevention. The full electronic search strategy for each database is presented in the electronic supplementary material (ESM 1). In addition, we
conducted a manual search by cross-checking references of review articles obtained through the electronic search. 2.2 Inclusion/Exclusion Criteria We first screened all records retrieved from the electronic databases based on abstracts and titles to determine inclusion in the review. Studies were included if they contained original analyses; reported cost-utility (e.g., cost per quality-adjusted life-years saved) or cost-effectiveness outcomes (e.g., cost per life-years saved, cost per HIV infection averted, and cost per new HIV diagnosis); made assessments based on US data; and evaluated one of the four HIV intervention types required by the health department funding announcement: (1) HIV testing, (2) prevention with HIV-positives and their partners, (3) condom distribution and (4) policy initiatives [6, 7]. Policy initiatives were described in the funding announcement as efforts to align structures, policies, and regulations with optimal HIV prevention, care, and treatment and to improve efficiency of HIV prevention efforts. One example was to address structural barriers to routine opt-out testing. Intervention types were further divided into subcategories in the funding announcement. For HIV testing, subcategories were: (1a) routine testing of patients ages 13–64 in healthcare settings, (1b) targeted testing programs in nonhealthcare settings, (1c) routine early HIV screening for all pregnant women, and (1d) screening for other sexually transmitted diseases, hepatitis, and tuberculosis in conjunction with HIV testing. Targeted testing refers to testing based on behavioral, clinical, or demographic characteristics. For prevention with HIV-positives, subcategories were: (2a) linkage to care and treatment, retention in care, (2b) behavioral interventions and other risk-reduction services, (2c) interventions to prevent mother-to-child HIV transmission, and (2d) referral to other medical and social services. The funding announcement included partner services in (2b), the ‘‘behavioral interventions and other riskreduction services’’ subcategory. In this review, however, we created a unique subcategory for partner services to facilitate comparisons with other interventions aimed at increasing the number of new HIV diagnoses. We excluded published abstracts and studies that estimated the hypothetical intervention costs and effects that could result in an intervention being cost effective (i.e., threshold analyses). We also excluded studies related to HIV testing that focused on technologies used for early diagnosis of acute HIV infection, testing programs in healthcare settings targeting patients with HIV risk factors and comparisons of testing technologies because these fell outside of the primary focus of the CDC funding priorities. Additionally, we excluded evaluations of interventions that
Cost Effectiveness of CDC-Funded HIV Prevention Interventions
no longer reflect standard of care, in particular, zidovudine monotherapy for preventing perinatal HIV transmission. For each eligible article, two reviewers independently extracted detailed information using a pre-specified 29-item abstraction form (see ESM 2) on key aspects of each analysis, sources of data, and cost-effectiveness result. The reviewers discussed any discrepancies in their independent abstractions and reached a consensus. We adjusted costs to 2011 US dollars, using the medical care component of the Consumer Price Index [8]. For studies that did not provide the year of cost calculation, we applied the year of publication. In our main results, we summarized the cost-effectiveness ratios for each intervention type and subcategory. We reported as many of the four previously described costeffectiveness metrics as were described in each study. We reported the number of studies (n) and the number of costeffectiveness outcomes (k) within each study. When more than one study reported a cost-effectiveness ratio for an intervention, we reported the range of ratios reported. We did not report mean or median of ratios because intervention implemented and methodologies used varied widely even under the same intervention type. We stratified costeffectiveness outcomes by the HIV prevalence (\1 %, 1–5 %, [5 %) of the population receiving the intervention when applicable.
3 Results Our comprehensive search yielded 4,633 records. We rejected 4,571 studies based on our inclusion criteria. Sixty-two articles were selected for full text review and upon review we excluded a further 12 (see ESM 3). We identified a total of 50 distinct studies as relevant and thus included them in the primary review (Fig. 1). We provide detailed information about each study in the electronic supplementary material (see ESM 4 Table), including individual cost-effectiveness ratios by intervention type, comparator strategy (including none), target population, types of costs included, settings, perspective, and analytic horizon. The year of publication for the included cost-effectiveness studies ranged from 1991 to 2012, with the majority published after 2000. We classified the 50 distinct studies under the four main intervention types: 33 studies related to HIV testing, 15 studies assessed prevention for HIV-positives, three reported on condom distribution and one reported on policy initiatives. Four studies evaluated multiple interventions or intervention subcategories, so the number of interventions evaluated exceeded the number of publications. The HIV testing studies were further classified as routine HIV screening in healthcare settings (22 of
Published articles and reports written in English identified through electronic databases and manual search (n=4,633)
Articles screened on basis of title and abstract
Out-of-scope (n=4,571): No cost-utility or cost-effectiveness outcomes reported (n=3,801) Review articles (n=127) Not US-based data (n=344) Interventions not of interest (n=299)
Included (n=62)
Full text review and application of exclusion criteria
Excluded (n=12)
Final studies included for primary review (n=50)
Fig. 1 Flow diagram of study selection
33), testing aimed at populations at higher risk of HIV infection in non-healthcare settings (7 of 33), early HIV screening of pregnant women (5 of 33), and screening for other diseases in conjunction with HIV (1 of 33). Under prevention for HIV-positives, the majority of studies evaluated partner services (9 of 15); two studies were identified for behavior interventions and for intervention to prevent mother-to-child HIV transmission; and only one study was identified for linkage to care and for referral to other medical and social services. The study of policy initiatives assessed the cost effectiveness of one law to deregulate access to syringes and one to increase alcohol taxes (Table 1). Of the 22 studies related to routine testing in healthcare settings, the most common setting evaluated was emergency departments and urgent care centers (9 studies). Other studies were conducted in hospital or primary care settings, STD clinics, the Veterans Administration, or did not specify the setting. Most of the studies found that it was cost effective (if compared to a US$100,000 per QALY threshold) or cost saving to routinely test for HIV in healthcare settings. Cost effectiveness ranged widely with HIV prevalence and it was more cost effective when the intervention was implemented for the population with a higher prevalence level (ESM 4). Methods used in the studies to determine outcomes varied. More than two-thirds employed mathematical
k
Range
n
Range
n
k
Cost per LY saved
Cost per QALY saved
5
1
1–5 % Prevalence
[5 % Prevalence 2
18
18 $23,000–$23,900
$19,500–$242,100
Cost saving–$1,854,600 –
2
3
1
[5 % Prevalence 3
2 2 $11,900–$70,200
$64,300–$66,500 Cost saving–$499,100 1
– –
–
1–5 % Prevalence
[5 % Prevalence
– –
–
– –
–
2 –
– –
– –
–
Cost saving–$15,200
$10,000–$28,200
2 3
– –
–
$16,700–$114,000
$10,500–$101,500
– –
–
6
7
–
–
–
–
–
–
1
$66,300
–
–
–
–
– –
– –
– –
– –
– – –
–
1
Cost saving
1
$77,400
1
[5 % Prevalence –
Cost saving
1 –
Cost saving
1
–
–
–
–
1
–
–
–
–
2
–
–
–
–
Cost saving–$2,800
– –
–
–
n number of studies, k number of cost-effectiveness outcomes, QALY quality-adjusted life years, LY life years
Multiple outcomes may be generated from one study
–
(4) Policy initiatives (n = 1) [11]
1
1–5 % Prevalence
(3) Condom distribution (n = 3) [10, 11, 70]
1
(2d) Referral to other medical and social services (n = 1) [69]
1
(2c) Intervention to prevent mother-to-child HIV transmission (n = 2) [67, 68]
1–5 % Prevalence [5 % Prevalence
(2b-1) Partner services (n = 9) [45, 59–66]
–
(2b) Behavior interventions and other risk-reduction services (n = 2) [57, 58]
1
(2a) Linkage to care and treatment, and interventions to improve retention in care (n = 1) [56]
(2) Prevention with HIV-positive individuals (n = 15)
\1 % Prevalence
(1d) Screening for other STD, hepatitis, and tuberculosis in conjunction with HIV testing (n = 1) [24]
–
–
\1 % Prevalence
(1c) Routine, early HIV screening for all pregnant women (n = 5) [51–55]
1 1
\1 % Prevalence 1–5 % Prevalence
(1b) Targeted testing programs in non-healthcare settings (n = 7) [44–50]
8
\1 % Prevalence
(1a) Routine testing of patients ages 13–64 in healthcare settings (n = 22) [14, 24–44]
(1) HIV testing (n = 33)
Intervention
Table 1 Summary of cost-effectiveness studies and outcomes by intervention (in US dollars)
1
–
2
–
1
1 –
2
–
2
–
2
–
2
3 –
3
–
–
–
– –
3
5
–
– –
–
–
4
k
2
4
–
– –
–
–
2
n
$6,000–$7,000
–
$31,000–$38,600
–
Cost saving–$186,300
$53,300–$54,500 –
$107,700–$535,800
–
–
–
Cost saving–cost saving
$53,500–$333,900
–
– –
–
–
$43,200–$348,000
Range
Cost per HIV infection averted
–
–
–
–
–
4 6
–
–
1
–
–
–
1
2 3
1
6
4
n
6
–
–
–
–
–
5 9
–
–
1
–
–
–
2
4 4
3
13
k
–
–
–
–
–
$3,100–$13,800 $3,200–$25,400
–
–
$11,800
–
–
–
$4,100–$9,400
$4,200–$31,300 $3,000–$21,000
$4,900–$7,500
$2,000–$30,500
$2,700–$13,500
Range
Cost per new HIV diagnosis
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Cost Effectiveness of CDC-Funded HIV Prevention Interventions
simulation models to estimate economic and epidemiological outcomes, rather than rely solely on empirical data. Due to the personal mode and relatively low rate of HIV transmission, models are often required for cost-effectiveness evaluation to translate intermediate outcomes relating services rendered, persons reached or condom usage into final outcomes or infections averted. In terms of costs, most studies assessed variable costs only (e.g., labor costs, cost of testing kits); less than 30 % included fixed costs (e.g., overheads, start-up costs). The majority of the studies did not conduct primary cost data collection, but instead estimated costs from other publications (ESM 4). We summarized the individual cost-effectiveness ratios and, when possible, ranges of ratios, across interventions and cost-effectiveness metrics (Table 1). Often only one study with one outcome was available for an intervention, and in many other cases, three or fewer studies were available. Studies reporting negative cost-effectiveness values were noted as cost saving. Cost per HIV infection averted was reported for at least one subcategory of each of the four key intervention types. The cost per new HIV diagnosis was reported for three of the four subcategories under HIV testing, as well as for the partner services subcategory. Overall, the outcomes of this metric fell in similar ranges across the subcategories. At the low prevalence level (\1 %), the cost of detecting a new HIV case fell within a smaller range for routine testing in healthcare settings (range = US$2,700–US$13,500, n = 4) than for targeted testing in non-healthcare settings (range = US$4,200–US$31,300, n = 2).
4 Discussion Our objective was to identify the extent to which the existing cost-effectiveness literature addressed the four key HIV prevention interventions required in the recent CDC HIV prevention funding announcement to health departments: HIV testing, prevention for HIV-positives, condom distribution, and policy initiatives. Of these prevention interventions, there is a growing body of literature on the cost effectiveness of HIV testing, particularly routine testing in healthcare settings. Forty-four percent (22 out of 50) of the studies included in our review were classified under that subcategory. The majority (14 out of 22) of those studies were published after 2006, following the issuance of CDC’s 2006 testing recommendation regarding routine HIV testing for all persons aged 13–64 years in healthcare settings [9]. Nearly one-fifth (9 out of 50) of the cost-effectiveness studies included in our review were classified under the partner services subcategory, with many of those published prior to 2000. Fewer than half of the studies included in our review belonged to the
remaining nine intervention subcategories, indicating paucity of cost-effectiveness evaluations related to prevention for HIV-positives, condom distribution, and policy initiatives. A number of reasons may explain the lack of economic evaluations for some interventions relative to others. Policy initiatives are difficult to evaluate with respect to costs and effectiveness. In regard to the latter, the effects of policy initiatives on changes in HIV transmission and acquisition also are difficult to quantify. The cost of condom distribution may be more readily estimated [10, 11], but assessing its effects requires detailed knowledge of the size of the associated increases in condom use, as well as of the risk factors among those who began using condoms more often or increased their use. Evaluating the efficacy of behavioral interventions for people living with HIV requires a reliance on self-reported risk behaviors before and after the delivery of an intervention and some studies are limited in follow-up periods to assess the duration of those effects. Assessing the costs of testing, including that associated with partner services, is relatively straightforward, as is documenting the number of new diagnoses associated with testing. The effects of a new diagnosis on enhanced life expectancy and reduced transmission, though more challenging, can be calculated based on empirical data on the likelihood of behavioral risk reduction and receipt of treatment, and the modeling of subsequent disease progression and transmission [12–14]. The diversity in methodology, assumptions, and models used to estimate the cost-effectiveness outcomes across studies and interventions makes it difficult to evaluate quality. Therefore, we did not attempt to assess the quality of the methods used to estimate costs or effectiveness. Standardization of model types and input data assumptions for translating intermediate outcomes into final outcomes would be helpful to generate comparable quality and outcomes across studies. In addition, though we reported individual cost-effectiveness ratios and ranges of ratios across similar interventions, these estimates should be interpreted with caution given the heterogeneity in the economic evaluation methods used, the data describing costs and effectiveness, and the populations and settings to which the interventions were applied. As one example, some of the included cost-effectiveness analyses were conducted in medium- or high-prevalence populations and settings, and therefore are not generalizable to low-prevalence settings. Moreover, the value of a certain type of intervention is likely underestimated if it is measured solely based on the number of HIV infections averted. One example is linkage to care and treatment, and interventions to improve retention, in which one of their major goals is to improve the health status and quality of life of infected persons, in addition to preventing new infections. Last, as
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is the case with all reviews of published studies, our findings may also be subject to publication selection bias. In spite of the heterogeneity among studies, this descriptive assessment is helpful in supporting policymakers or those charged with HIV resource allocation decisions in several ways. First, it identifies the body of evidence of cost effectiveness for the various interventions considered. And, where lacking, this review encourages decision-makers to seek local data on the costs and outcomes of HIV programs. These data could then be used to map out an evidenced-based HIV intervention portfolio. Funding decisions are typically influenced by a myriad of factors including historical spending, epidemic data, stakeholder pressures and other non-quantifiable factors; with this study, we expect to further inform this decisionmaking process. Our cost-effectiveness findings include interventions specified in CDC’s health department funding announcement for HIV prevention, and do not represent the full costeffectiveness literature on HIV prevention. For instance, there is a growing body of literature on the cost effectiveness of diagnosing acute and early HIV infection [13, 15, 16]. These studies generally support using highly sensitive HIV testing technologies to enable early identification of infection and eliminate onward transmission of acute HIV infection in high-incidence settings. Also not included were studies that evaluated late-stage perinatal testing which is also supported by cost-effectiveness evidence [17]. Additionally, we did not evaluate intervention strategies that have been shown to be promising in recent model-based studies, such as pre-exposure prophylaxis [16, 18–20] and treatment as prevention [21–23]. In summary, our analysis highlights the extent to which the published cost-effectiveness literature supports four key HIV prevention interventions recommended by CDC, and suggests areas where evaluations are limited. With the exception of HIV testing-related interventions, including partner services, where economic evaluations suggest that testing is cost effective in most cases, more cost-effectiveness research is needed to fill the knowledge gaps of interventions related to prevention for HIV-positives, condom distribution, and policy initiatives, in order to help guide the most efficient use of resources. Acknowledgments We sincerely thank Christy Cechman and Barbara Landreth for their help on our literature search. We also thank Paul Farnham, Ram Shrestha, Feng Lin, Chaitra Gopalappa, Robert Koppenhaver, Stephen Sorenson, Steve Nesheim, and Allan Taylor for their help in reviewing and abstracting studies. Funding and conflict of interest The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. No sources of funding were used to conduct this study or to prepare this
manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review. Author contributions Conception and design: YLH, AL, SLS; data collection: YLH, AL; analysis and interpretation: YLH, AL, AH, SLS; writing the article: YLH; critical revision of the article: AL, AH, SLS; overall responsibility: YLH.
References 1. Farnham PG, Holtgrave DR, Sansom SL, Hall HI. Medical costs averted by HIV prevention efforts in the United States, 1991–2006. J Acquir Immune Defic Syndr. 2010;54(5):565–7. 2. Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520–9. 3. Prejean J, Song R, Hernandez A, Ziebell R, Green T, Walker F, et al. Estimated HIV incidence in the United States, 2006–2009. PloS One. 2011;6(8):e17502. 4. Hall HI, Green TA, Wolitski RJ, Holtgrave DR, Rhodes P, Lehman JS, et al. Estimated future HIV prevalence, incidence, and potential infections averted in the United States: a multiple scenario analysis. J Acquir Immune Defic Syndr. 2010;55(2): 271–6. 5. National HIV/AIDS Strategy for the United States. Office of National AIDS Policy; 2010. 6. CDC. Funding Opportunity Announcement (FOA) PS12-1201: Comprehensive HIV Prevention Programs for Health Departments [cited 8/15/2012]. Available from: http://www.cdc.gov/ hiv/topics/funding/PS12-1201/. 7. CDC. CDC’S New High-Impact Approach to HIV Prevention Funding for Health Departments. Advancing the National HIV/ AIDS Strategy [cited 5/11/2012]. Available from: http://www. cdc.gov/hiv/topics/funding/PS12-1201/resources/factsheet/pdf/ foa-partner.pdf. 8. Bureau of Labor Statistics. Medical Care Consumer Price Index [cited]. Available from: http://data.bls.gov/cgi-bin/survey most?cu. 9. Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1–17. 10. Bedimo AL, Pinkerton SD, Cohen DA, Gray B, Farley TA. Condom distribution: a cost-utility analysis. Int J STD AIDS. 2002;13(6):384–92. 11. Cohen DA, Wu SY, Farley TA. Structural interventions to prevent HIV/sexually transmitted disease: are they cost-effective for women in the southern United States? Sex Transm Dis. 2006;33(7 Suppl):S46–9. 12. Prabhu VS, Hutchinson AB, Farnham PG, Sansom SL. Sexually acquired HIV infections in the United States due to acute-phase HIV transmission: an update. AIDS. 2009;23(13):1792–4. 13. Hutchinson AB, Patel P, Sansom SL, Farnham PG, Sullivan TJ, Bennett B, et al. Cost-effectiveness of pooled nucleic acid amplification testing for acute HIV infection after third-generation HIV antibody screening and rapid testing in the United States: a comparison of three public health settings. PLoS Med. 2010;7(9):e1000342. 14. Farnham PG, Sansom SL, Hutchinson AB. How much should we pay for a new HIV diagnosis? A mathematical model of HIV screening in US clinical settings. Med Decis Making. 2012;32(3):459–69.
Cost Effectiveness of CDC-Funded HIV Prevention Interventions 15. Long EF. HIV screening via fourth-generation immunoassay or nucleic acid amplification test in the United States: a costeffectiveness analysis. PloS One. 2011;6(11):16. 16. Juusola JL, Brandeau ML, Long EF, Owens DK, Bendavid E. The cost-effectiveness of symptom-based testing and routine screening for acute HIV infection in men who have sex with men in the USA. AIDS. 2011;25(14):1779–87. 17. Sansom SL, Jamieson DJ, Farnham PG, Bulterys M, Fowler MG. Human immunodeficiency virus retesting during pregnancy: costs and effectiveness in preventing perinatal transmission. Obstet Gynecol. 2003;102(4):782–90. 18. Desai K, Sansom SL, Ackers ML, Stewart SR, Hall HI, Hu DJ, et al. Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness. AIDS. 2008;22(14): 1829–39. 19. Paltiel AD, Freedberg KA, Scott CA, Schackman BR, Losina E, Wang B, et al. HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and costeffectiveness. Clin Infect Dis. 2009;48(6):806–15. 20. Koppenhaver RT, Sorensen SW, Farnham PG, Sansom SL. The cost-effectiveness of pre-exposure prophylaxis in men who have sex with men in the United States: an epidemic model. J Acquir Immune Defic Syndr. 2011;58(2):e51–2. 21. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373(9657):48–57. 22. Walensky RP, Ross EL, Kumarasamy N, Wood R, Noubary F, Paltiel AD, et al. The cost-effectiveness of treatment as prevention: analysis of the HPTN 052 trial. International AIDS Conference. Washington DC, US; 2012. 23. Granich R, Kahn JG, Bennett R, Holmes CB, Garg N, Serenata C, et al. Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011–2050. PLoS One. 2012;7(2):e30216. 24. Silva A, Glick NR, Lyss SB, Hutchinson AB, Gift TL, Pealer LN, et al. Implementing an HIV and sexually transmitted disease screening program in an emergency department. Ann Emerg Med. 2007;49(5):564–72. 25. Lurie P, Avins AL, Phillips KA, Kahn JG, Lowe RA, Ciccarone D. The cost-effectiveness of voluntary counseling and testing of hospital inpatients for HIV infection. JAMA. 1994;272(23): 1832–8. 26. Owens DK, Nease RF Jr, Harris RA. Cost-effectiveness of HIV screening in acute care settings. Arch Intern Med. 1996;156(4): 394–404. 27. Phillips KA, Fernyak S. The cost-effectiveness of expanded HIV counselling and testing in primary care settings: a first look. AIDS. 2000;14(14):2159–69. 28. Walensky RP, Weinstein MC, Kimmel AD, Seage GR 3rd, Losina E, Sax PE, et al. Routine human immunodeficiency virus testing: an economic evaluation of current guidelines. Am J Med. 2005;118(3):292–300. 29. Walensky RP, Losina E, Malatesta L, Barton GE, O’Connor CA, Skolnik PR, et al. Effective HIV case identification through routine HIV screening at urgent care centers in Massachusetts. Am J Public Health. 2005;95(1):71–3. 30. Sanders GD, Bayoumi AM, Sundaram V, Bilir SP, Neukermans CP, Rydzak CE, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med. 2005;352(6):570–85. 31. Paltiel AD, Weinstein MC, Kimmel AD, Seage GR 3rd, Losina E, Zhang H, et al. Expanded screening for HIV in the United States—an analysis of cost-effectiveness. N Engl J Med. 2005;352(6):586–95.
32. Paltiel AD, Walensky RP, Schackman BR, Seage GR 3rd, Mercincavage LM, Weinstein MC, et al. Expanded HIV screening in the United States: effect on clinical outcomes, HIV transmission, and costs. Ann Intern Med. 2006;145(11):797–806. 33. Holtgrave DR. Costs and consequences of the US Centers for Disease Control and Prevention’s recommendations for opt-out HIV testing. PLoS Med. 2007;4(6):e194. 34. Brown J, Shesser R, Simon G, Bahn M, Czarnogorski M, Kuo I, et al. Routine HIV screening in the emergency department using the new US Centers for Disease Control and Prevention Guidelines: results from a high-prevalence area. J Acquir Immune Defic Syndr. 2007;46(4):395–401. 35. Farnham PG, Hutchinson AB, Sansom SL, Branson BM. Comparing the costs of HIV screening strategies and technologies in health-care settings. Public Health Rep. 2008;123(Suppl 3):51–62. 36. Sanders GD, Bayoumi AM, Holodniy M, Owens DK. Costeffectiveness of HIV screening in patients older than 55 years of age. Ann Intern Med. 2008;148(12):889–903. 37. Long EF, Brandeau ML, Owens DK. The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Ann Intern Med. 2010;153(12):778–89. 38. Sanders GD, Anaya HD, Asch S, Hoang T, Golden JF, Bayoumi AM, et al. Cost-effectiveness of strategies to improve HIV testing and receipt of results: economic analysis of a randomized controlled trial. J Gen Intern Med. 2010;25(6):556–63. 39. Torres GW, Heffelfinger JD, Pollack HA, Barrera SG, Rothman RE. HIV screening programs in US emergency departments: a cross-site comparison of structure, process, and outcomes. Ann Emerg Med. 2011;58(1 Suppl 1):S104–13. 40. Hsieh YH, Jung JJ, Shahan JB, Pollack HA, Hairston HS, Moring-Parris D, et al. Outcomes and cost analysis of 3 operational models for rapid HIV testing services in an academic inner-city emergency department. Ann Emerg Med. 2011;58(1 Suppl 1):S133–9. 41. Hutchinson AB, Farnham PG, Lyss SB, White DA, Sansom SL, Branson BM. Emergency department HIV screening with rapid tests: a cost comparison of alternative models. AIDS Educ Prev. 2011;23(3 Suppl):58–69. 42. Prabhu VS, Farnham PG, Hutchinson AB, Soorapanth S, Heffelfinger JD, Golden MR, et al. Cost-effectiveness of HIV screening in STD clinics, emergency departments, and inpatient units: a model-based analysis. PLoS One. 2011;6(5):e19936. 43. Walensky RP, Morris BL, Reichmann WM, Paltiel AD, Arbelaez C, Donnell-Fink L, et al. Resource utilization and cost-effectiveness of counselor- vs. provider-based rapid point-of-care HIV screening in the emergency department. PLoS One. 2011;6(10):12. 44. Shrestha RK, Clark HA, Sansom SL, Song B, Buckendahl H, Calhoun CB, et al. Cost-effectiveness of finding new HIV diagnoses using rapid HIV testing in community-based organizations. Public Health Rep. 2008;123(Suppl 3):94–100. 45. Golden MR, Gift TL, Brewer DD, Fleming M, Hogben M, St Lawrence JS, et al. Peer referral for HIV case-finding among men who have sex with men. AIDS. 2006;20(15):1961–8. 46. Varghese B, Peterman TA. Cost-effectiveness of HIV counseling and testing in US prisons. J Urban Health. 2001;78(2):304–12. 47. Shrestha RK, Sansom SL, Richardson-Moore A, French PT, Scalco B, Lalota M, et al. Costs of voluntary rapid HIV testing and counseling in jails in 4 states—advancing HIV Prevention Demonstration Project, 2003–2006. Sex Transm Dis. 2009;36(2 Suppl):S5–8. 48. Shrestha RK, Sansom SL, Schulden JD, Song B, Smith LC, Ramirez R, et al. Costs and effectiveness of finding new HIV diagnoses by using rapid testing in transgender communities. AIDS Educ Prev. 2011;23(3 Suppl):49–57.
Y.-L. A. Huang et al. 49. Schackman BR, Metsch LR, Colfax GN, Leff JA, Wong A, Scott CA, et al. The cost-effectiveness of rapid HIV testing in substance abuse treatment: results of a randomized trial. Drug Alcohol Depend. 2012;6:6. 50. Cipriano LE, Zaric GS, Holodniy M, Bendavid E, Owens DK, Brandeau ML. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users. PLoS One. 2012;7(9):18. 51. Grobman WA, Garcia PM. The cost-effectiveness of voluntary intrapartum rapid human immunodeficiency virus testing for women without adequate prenatal care. Am J Obstet Gynecol. 1999;181(5 Pt 1):1062–71. 52. Immergluck LC, Cull WL, Schwartz A, Elstein AS. Cost-effectiveness of universal compared with voluntary screening for human immunodeficiency virus among pregnant women in Chicago. Pediatrics. 2000;105(4):E54. 53. Zaric GS, Bayoumi AM, Brandeau ML, Owens DK. The cost effectiveness of voluntary prenatal and routine newborn HIV screening in the United States. J Acquir Immune Defic Syndr. 2000;25(5):403–16. 54. Resch S, Altice FL, Paltiel AD. Cost-effectiveness of HIV screening for incarcerated pregnant women. J Acquir Immune Defic Syndr. 2005;38(2):163–73. 55. Myers ER, Thompson JW, Simpson K. Cost-effectiveness of mandatory compared with voluntary screening for human immunodeficiency virus in pregnancy. Obstet Gynecol. 1998;91(2): 174–81. 56. Gopalappa C, Farnham PG, Hutchinson AB, Sansom SL. Cost effectiveness of the National HIV/AIDS Strategy goal of increasing linkage to care for HIV-infected persons. J Acquir Immune Defic Syndr. 2012;61(1):99–105. 57. Lee MB, Leibowitz A, Rotheram-Borus MJ. Cost-effectiveness of a behavioral intervention for seropositive youth. AIDS Educ Prev. 2005;17(2):105–18. 58. Marseille E, Shade SB, Myers J, Morin S. The cost-effectiveness of HIV prevention interventions for HIV-infected patients seen in clinical settings. J Acquir Immune Defic Syndr. 2011;56(3): e87–94. 59. Rutherford GW, Woo JM, Neal DP, Rauch KJ, Geoghegan C, McKinney KC, et al. Partner notification and the control of human immunodeficiency virus infection. Two years of experience in San Francisco. Sex Transm Dis. 1991;18(2):107–10.
60. Pavia AT, Benyo M, Niler L, Risk I. Partner notification for control of HIV: results after 2 years of a statewide program in Utah. Am J Public Health. 1993;83(10):1418–24. 61. Spencer NE, Hoffman RE, Raevsky CA, Wolf FC, Vernon TM. Partner notification for human immunodeficiency virus infection in Colorado: results across index case groups and costs. Int J STD AIDS. 1993;4(1):26–32. 62. Toomey KE, Peterman TA, Dicker LW, Zaidi AA, Wroten JE, Carolina J. Human immunodeficiency virus partner notification. Cost and effectiveness data from an attempted randomized controlled trial. Sex Transm Dis. 1998;25(6):310–6. 63. Varghese B, Peterman TA, Holtgrave DR. Cost-effectiveness of counseling and testing and partner notification: a decision analysis. AIDS. 1999;13(13):1745–51. 64. Ahrens K, Kent CK, Kohn RP, Nieri G, Reynolds A, Philip S, et al. HIV partner notification outcomes for HIV-infected patients by duration of infection, San Francisco, 2004–2006. J Acquir Immune Defic Syndr. 2007;46(4):479–84. 65. Shrestha RK, Begley EB, Hutchinson AB, Sansom SL, Song B, Voorhees K, et al. Costs and effectiveness of partner counseling and referral services with rapid testing for HIV in Colorado and Louisiana, United States. Sex Transm Dis. 2009;36(10):637–41. 66. Shrestha RK, Sansom SL, Kimbrough L, Hutchinson AB, Daltry D, Maldonado W, et al. Cost-effectiveness of using social networks to identify undiagnosed HIV infection among minority populations. J Public Health Manag Pract. 2010;16(5):457–64. 67. Halpern MT, Read JS, Ganoczy DA, Harris DR. Cost-effectiveness of cesarean section delivery to prevent mother-to-child transmission of HIV-1. AIDS. 2000;14(6):691–700. 68. Mrus JM, Goldie SJ, Weinstein MC, Tsevat J. The cost-effectiveness of elective Cesarean delivery for HIV-infected women with detectable HIV RNA during pregnancy. AIDS. 2000;14(16):2543–52. 69. Holtgrave DR, Wolitski RJ, Pals SL, Aidala A, Kidder DP, Vos D, et al. Cost-utility analysis of the housing and health intervention for homeless and unstably housed persons living with HIV. AIDS Behav. 2012;16:16. 70. Holtgrave DR, Maulsby C, Kharfen M, Jia Y, Wu C, Opoku J, et al. Cost-utility analysis of a female condom promotion program in Washington,DC. AIDS Behav. 2012;16(5):1115–20.
