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Journal ArticleDOI

HIV Treatment as Prevention: Issues in Economic Evaluation

10 Jul 2012-PLOS Medicine (Public Library of Science)-Vol. 9, Iss: 7

TL;DR: Economic evaluations of antiretroviral therapy in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope of delivery.

AbstractMeyer-Rath and Over assert in another article in the July 2012 PLoS Medicine Collection, “Investigating the Impact of Treatment on New HIV Infections”, that economic evaluations of antiretroviral therapy (ART) in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope of delivery, health states, ART regimens, health workers' experience, patients' time on treatment, and the distribution of delivery across public and private sectors. We argue that for particular evaluation purposes (e.g., to establish the social value of TasP) and from particular perspectives (e.g., national health policy makers) less detailed cost functions may be sufficient. We then extend the discussion of economic evaluation of TasP, describing why ART outcomes and costs assessed in currently existing programs are unlikely to be generalizable to TasP programs for several fundamental reasons. First, to achieve frequent, widespread HIV testing and high uptake of ART immediately following an HIV diagnosis, TasP programs will require components that are not present in current ART programs and whose costs are not included in current estimates. Second, the early initiation of ART under TasP will change not only patients' disease courses and treatment experiences—which can affect behaviors that determine clinical treatment success, such as ART adherence and retention—but also quality of life and economic outcomes for HIV-infected individuals. Third, the preventive effects of TasP are likely to alter the composition of the HIV-infected population over time, changing its biological and behavioral characteristics and leading to different costs and outcomes for ART.

Topics: Economic evaluation (52%), Population (51%), Health economics (50%)

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Citations
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Journal ArticleDOI
01 Mar 2014-AIDS
TL;DR: A rapid systematic review of the global evidence on interventions that can improve adherence to ART, including individual-level interventions and changes to the structure of ART delivery, to inform the evidence base for the 2013 WHO consolidated antiretroviral guidelines.
Abstract: Introduction: Access to antiretroviral treatment (ART) has substantially improved over the past decade. In this new era of HIV as a chronic disease, the continued success of ART will depend critically on sustained high ART adherence. The objective of this review was to systematically review interventions that can improve adherence to ART, including individual-level interventions and changes to the structure of ART delivery, to inform the evidence base for the 2013 WHO consolidated antiretroviral guidelines. Design: A rapid systematic review. Methods: We conducted a rapid systematic review of the global evidence on interventions to improve adherence to ART, utilizing pre-existing systematic reviews to identify relevant research evidence complemented by screening of databases for articles published over the past 2 years on evidence from randomized controlled trials (RCTs). We searched five databases for both systematic reviews and primary RCT studies (Cochrane Library, EMBASE, MEDLINE, Web of Science, and WHO Global Health Library); we additionally searched ClinicalTrials.gov for RCT studies. We examined intervention effectiveness by different study characteristics, in particular, the specific populations who received the intervention. Results: A total of 124 studies met our selection criteria. Eighty-six studies were RCTs. More than 20 studies have tested the effectiveness of each of the following interventions, either singly or in combination with other interventions: cognitive-behavioural interventions, education, treatment supporters, directly observed therapy, and active adherence reminder devices (such as mobile phone text messages). Although there is strong evidence that all five of these interventions can significantly increase ART adherence in some settings, each intervention has also been found not to produce significant effects in several studies. Almost half (55) of the 124 studies investigated the effectiveness of combination interventions. Combination interventions tended to have effects that were similar to those of single interventions. The evidence base on interventions in key populations was weak, with the exception of interventions for people who inject drugs. Conclusion: Tested and effective adherence-enhancing interventions should be increasingly moved into implementation in routine programme and care settings, accompanied by rigorous evaluation of implementation impact and performance. Major evidence gaps on adherence-enhancing interventions remain, in particular, on the cost-effectiveness of interventions in different settings, long-term effectiveness, and effectiveness of interventions in specific populations, such as pregnant and breastfeeding women.

190 citations


Journal ArticleDOI
TL;DR: A new mathematical model is developed and applied to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009–2020.
Abstract: The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a “game changer” in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/μL. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009–2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa’s current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer.

80 citations


Cites background from "HIV Treatment as Prevention: Issues..."

  • ...possibility that our analysis confirms TasP to be a game changer, because TasP is likely to require additional program components that are not part of current ART programs, such as intensified HIV testing campaigns (11)....

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  • ...Compounding such uncertainties is the fact that we do not yet have reliable estimates of the resources needed for implementing TasP, nor of its population-level benefits (11)....

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  • ...TasP on morbidity and quality of life, and on economic and social outcomes, in South Africa are currently largely unknown, but in the longer run may be similar to those of ART (11)....

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  • ..., frequent testing and retesting for HIV and ensuring high ART uptake among HIV-infected people who are not yet suffering significant symptoms (11)....

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Journal ArticleDOI
TL;DR: This work describes the current uses for phylogenetics in generalized epidemics and discusses their promise for elucidating transmission patterns and informing prevention trials, and reviews logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized Epidemics and suggest potential solutions.
Abstract: Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics and suggest potential solutions.

77 citations


Cites background from "HIV Treatment as Prevention: Issues..."

  • ...To sustain an ongoing ART scale-up, and the potential widespread implementation of TasP in the future, expanded financial and public health resources will be required.(7,8) However, the most biologically effective and financially efficient way...

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Journal ArticleDOI
TL;DR: It is hoped that this article will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention.
Abstract: Antiretroviral therapy (ART) for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to guide policy decisions about the role of ART in reducing HIV incidence. Epidemiology, economics, demography, statistics, biology, and mathematical modelling will be central in framing key decisions in the optimal use of ART. PLoS Medicine, with the HIV Modelling Consortium, has commissioned a set of articles that examine different aspects of HIV treatment as prevention with a forward-looking research agenda. Interlocking themes across these articles are discussed in this introduction. We hope that this article, and others in the collection, will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention.

66 citations


Journal ArticleDOI
02 Jan 2013-AIDS
TL;DR: If IHC use increases HIV acquisition risk, reducing IHC could reduce new HIV infections; however, this must be balanced against other important consequences, including unintended pregnancy, which impacts maternal and infant mortality.
Abstract: BACKGROUND: Some but not all observational studieshave suggested an increase in risk of HIV acquisition for women using injectable hormonal contraception (IHC). METHODS: We used country-level data to explore the effects of reducing IHC use on the number of HIV infections the number of live births and the resulting net consequenceson AIDS deaths and maternal mortality for each country. RESULTS: High IHC use coincides with high HIV incidence primarily in southern and eastern Africa. If IHC does increase the risk of HIV acquisition this could generate 27 000-130 000 infections per year globally 87-88% of which occur in this region. Reducing IHC use could result in fewer HIV infections but also a substantial increase in live births and maternal mortality in countries with high IHC use high birth rates and high maternal mortality: mainly southern and eastern Africa South-East Asia and Central and South America. For most countries the net impactof reducing IHC use on maternal and AIDS-related deaths is dependent on the magnitude of the assumed IHC-HIV interaction. CONCLUSIONS: If IHC use increases HIV acquisition risk reducing IHC could reduce new HIV infections; however this must be balanced against other important consequences including unintended pregnancy which impacts maternal and infant mortality. Unless the true effect size approaches a relative risk of 2.19 it is unlikely that reductions in IHC could result in public health benefit with the possible exception of those countries in southern Africa with the largest HIV epidemics.

66 citations


References
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Journal ArticleDOI
Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

5,521 citations


Journal ArticleDOI
TL;DR: These Guidelines were developed by the Panel* on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation.
Abstract: SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

4,315 citations


Journal ArticleDOI
TL;DR: The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.
Abstract: MS Cohen, YQ Chen, M McCauley N Engl J Med 2011 365:493–505. The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.1 ,2 It has long been known that the probability of sexual transmission of HIV is strongly correlated with concentrations of HIV in blood and genital fluids.3 ,4 Effective antiretroviral therapy (ART) produces prolonged and sustained suppression of HIV replication in these compartments, reducing the amount of free virus.5 ,6 Thus, there has long been a …

4,082 citations


"HIV Treatment as Prevention: Issues..." refers result in this paper

  • ...The results from the HTPN 052 trial reported in August 2011 demonstrated under the controlled conditions of a well-conducted clinical trial that early antiretroviral therapy (ART) can be highly effective in preventing transmission of HIV in stable heterosexual HIV-discordant couples [1]....

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Journal ArticleDOI
TL;DR: A theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics.
Abstract: Summary Background Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6·7 million were still in need of treatment and a further 2·7 million became infected with HIV in 2007. Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination. Methods We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive. We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual. Findings The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years. It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US$1·7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease. Interpretation Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics. This approach merits further mathematical modelling, research, and broad consultation. Funding None.

1,877 citations


"HIV Treatment as Prevention: Issues..." refers background in this paper

  • ...Of course, the specific components required for successful TasP will depend on the particular TasP intervention strategy—universal population-wide HIV testing and treatment will use different approaches, and incur different costs, than TasP strategies targeted at people at high risk of HIV transmission, such as HIV-infected individuals in HIV-discordant couples [2,13,20]....

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  • ...[13] assert based on their modeling results, the economic case for TasP would likely be robust to large increases in the cost estimates....

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  • ...[13], it may not alter the overall conclusion that TasP is a socially worthwhile intervention....

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  • ...[13] ‘‘for scale and a plausible pattern of distribution of patients into clinics’’ [8]....

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Journal ArticleDOI
Abstract: Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/ml and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. Please see later in the article for the Editors’ Summary.

344 citations


Additional excerpts

  • ...A few mathematical modeling studies have predicted the cost-effectiveness of TasP, using cost estimates derived from currently existing ART programs [4–7]....

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