The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study

Background

HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.

Methods and Findings

We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.

Conclusions

A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors'' Summary     

Effectiveness and Cost Effectiveness of Oral Pre-Exposure Prophylaxis in a Portfolio of Prevention Programs for Injection Drug Users in Mixed HIV Epidemics

Background

Pre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP in various combinations with methadone maintenance treatment (MMT) and antiretroviral treatment (ART) in Ukraine, a representative case for mixed HIV epidemics.

Methods and Findings

We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs in MMT, adding an oral PrEP program (tenofovir/emtricitabine, 49% susceptibility reduction) for uninfected IDUs. We analyzed intervention portfolios consisting of oral PrEP (25% or 50% of uninfected IDUs), MMT (25% of IDUs), and ART (80% of all eligible patients). We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness. A combination of PrEP for 50% of IDUs and MMT lowered HIV prevalence the most in both IDUs and the general population. ART combined with MMT and PrEP (50% access) averted the most infections (14,267). For a PrEP cost of $950, the most cost-effective strategy was MMT, at $520/QALY gained versus no intervention. The next most cost-effective strategy consisted of MMT and ART, costing $1,000/QALY gained compared to MMT alone. Further adding PrEP (25% access) was also cost effective by World Health Organization standards, at $1,700/QALY gained. PrEP alone became as cost effective as MMT at a cost of $650, and cost saving at $370 or less.

Conclusions

Oral PrEP for IDUs can be part of an effective and cost-effective strategy to control HIV in regions where injection drug use is a significant driver of the epidemic. Where budgets are limited, focusing on MMT and ART access should be the priority, unless PrEP has low cost.     

HIV screening via fourth-generation immunoassay or nucleic acid amplification test in the United States: a cost-effectiveness analysis

Background

At least 10% of the 56,000 annual new HIV infections in the United States are caused by individuals with acute HIV infection (AHI). It unknown whether the health benefits and costs of routine nucleic acid amplification testing (NAAT) are justified, given the availability of newer fourth-generation immunoassay tests.

Methods

Using a dynamic HIV transmission model instantiated with U.S. epidemiologic, demographic, and behavioral data, I estimated the number of acute infections identified, HIV infections prevented, quality-adjusted life years (QALYs) gained, and the cost-effectiveness of alternative screening strategies. I varied the target population (everyone aged 15-64, injection drug users [IDUs] and men who have sex with men [MSM], or MSM only), screening frequency (annually, or every six months), and test(s) utilized (fourth-generation immunoassay only, or immunoassay followed by pooled NAAT).

Results

Annual immunoassay testing of MSM reduces incidence by 9.5% and costs <$10,000 per QALY gained. Adding pooled NAAT identifies 410 AHI per year, prevents 9.6% of new cases, costs $92,000 per QALY gained, and remains <$100,000 per QALY gained in settings where undiagnosed HIV prevalence exceeds 4%. Screening IDUs and MSM annually with fourth-generation immunoassay reduces incidence by 13% with cost-effectiveness <$10,000 per QALY gained. Increasing the screening frequency to every six months reduces incidence by 11% (MSM only) or 16% (MSM and IDUs) and costs <$20,000 per QALY gained.

Conclusions

Pooled NAAT testing every 12 months of MSM and IDUs in the United States prevents a modest number of infections, but may be cost-effective given sufficiently high HIV prevalence levels. However, testing via fourth-generation immunoassay every six months prevents a greater number of infections, is more economically efficient, and may obviate the benefits of acute HIV screening via NAAT.     

Access to Healthcare,HIV/STI Testing,and Preferred Pre-Exposure Prophylaxis Providers among Men Who Have Sex with Men and Men Who Engage in Street-Based Sex Work in the US

Background

Pre-exposure prophylaxis (PrEP) is a promising strategy for HIV prevention among men who have sex with men (MSM) and men who engage in sex work. But access will require routine HIV testing and contacts with healthcare providers. This study investigated men’s healthcare and HIV testing experiences to inform PrEP implementation.

Methods

We conducted 8 focus groups (n = 38) in 2012 and 56 in-depth qualitative interviews in 2013–14 with male sex workers (MSWs) (n = 31) and other MSM (n = 25) in Providence, RI. MSWs primarily met clients in street-based sex work venues. Facilitators asked participants about access to healthcare and HIV/STI testing, healthcare needs, and preferred PrEP providers.

Results

MSWs primarily accessed care in emergency rooms (ERs), substance use clinics, correctional institutions, and walk-in clinics. Rates of HIV testing were high, but MSWs reported low access to other STI testing, low insurance coverage, and unmet healthcare needs including primary care, substance use treatment, and mental health services. MSM not engaging in sex work were more likely to report access to primary and specialist care. Rates of HIV testing among these MSM were slightly lower, but they reported more STI testing, more insurance coverage, and fewer unmet needs. Preferred PrEP providers for both groups included primary care physicians, infectious disease specialists, and psychiatrists. MSWs were also willing to access PrEP in substance use treatment and ER settings.

Conclusions

PrEP outreach efforts for MSWs and other MSM should engage diverse providers in many settings, including mental health and substance use treatment, ERs, needle exchanges, correctional institutions, and HIV testing centers. Access to PrEP will require financial assistance, but can build on existing healthcare contacts for both populations.     

Cost-Effectiveness of Pre-Exposure Prophylaxis (PrEP) in Preventing HIV-1 Infections in Rural Zambia: A Modeling Study

Background

Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia.

Methods

A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4<350 cells/mm³. We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5–15% of the total population), versus randomly putting 40–60% of the total population on PrEP.

Results

Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios.

Conclusions

Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect.     

Acceptability of Pre-Exposure Prophylaxis among Men Who Have Sex with Men and Transgender Women in Northern Thailand

Background

Northern Thailand has a high burden HIV epidemic among MSM and TG. Oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine has demonstrated efficacy in preventing HIV among MSM and TG in Chiang Mai, Thailand. Determinants of PrEP acceptability are needed to gauge the potential uptake of this prevention strategy.

Methods

From January to February 2012, 238 MSM and TG participants, who self-reported as HIV-uninfected or of unknown status, completed a self-administered survey on hand-held computers. Participants were recruited by venue-day-time sampling and asked to rate their likelihood of using oral PrEP for HIV prevention with an efficacy of 50%. PrEP acceptability was defined as being “very likely” to use PrEP. Odds ratios and 95% CIs were calculated to identify correlates of acceptability.

Results

131 MSM and 107 TG responded, with mean ages of 23.7 and 21.8, respectively. 24% of MSM engaged primarily in receptive anal sex vs. 74% of TG. 21% of MSM and 44% of TG reported regular medication use. Prior awareness of PrEP was high at 66% among both MSM and TG respondents. 41% of MSM and 37% of TG were "very likely" to use PrEP. Among MSM, factors associated with PrEP acceptability included a prior history of STIs (AOR 4.6; 95%CIs 1.7-12.6), previous HIV testing (AOR 2.4 95%CIs 1.1-5.3), regularly planned sex (AOR 2.8 95%CIs 1.1-7.2), and infrequent sex (AOR 2.9 95%CIs 1.3-6.3). Among TG, factors associated with acceptability included prior awareness of PrEP (AOR 3.3; 95%CIs 1.2-9.0) and having private insurance (AOR 5.0; 95%CIs 1.3-19.0).

Conclusion

MSM and TG in Northern Thailand are distinct groups in terms of sexual behaviors, patterns of medication use, and correlates of PrEP acceptability. Efforts to maximize PrEP uptake should include expanded HIV testing services and the provision of financial subsidies to reduce the cost of PrEP.     

HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

Background

We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART).

Methods

We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY.

Results

For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.

Conclusions

Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.     

The Potential Cost and Benefits of Raltegravir in Simplified Second-Line Therapy among HIV Infected Patients in Nigeria and South Africa

Background

There is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa.

Methods

We developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained.

Results

Reducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL.

Conclusions

The combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria.     

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection

Background

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.

Methods

Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.

Results

Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.

Conclusions

While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.     

Cost Effectiveness of Screening Strategies for Early Identification of HIV and HCV Infection in Injection Drug Users

Objective

To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs) in opioid replacement therapy (ORT).

Design

Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15–59).

Methods

We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).

Results

Adding HIV and HCV viral RNA testing to antibody testing averts 14.8–30.3 HIV and 3.7–7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.

Discussion

Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3–6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.     

Resource utilization and cost-effectiveness of counselor- vs. provider-based rapid point-of-care HIV screening in the emergency department

Background

Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.

Methods

We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.

Results

Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.

Conclusions

The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services.     

The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies

Background

Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions.

Methods and Findings

We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP.

Conclusions

Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors'' Summary     

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction

Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women.

Methods

Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of “no screening” and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed.

Results

Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated.

Conclusions

Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less.     

Cost-Effectiveness of Enhanced Syphilis Screening among HIV-Positive Men Who Have Sex with Men: A Microsimulation Model

Background

Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population.

Purpose

We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care.

Methods

We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer.

Results

Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV.

Conclusions

We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this group (i.e., for viral load monitoring) makes intensification of syphilis screening appear readily practicable.     

Evaluating the cost-effectiveness of pre-exposure prophylaxis (PrEP) and its impact on HIV-1 transmission in South Africa

Background

Mathematical modelers have given little attention to the question of how pre-exposure prophylaxis (PrEP) may impact on a generalized national HIV epidemic and its cost-effectiveness, in the context of control strategies such as condom use promotion and expanding ART programs.

Methodology/Principal Findings

We use an age- and gender-structured model of the generalized HIV epidemic in South Africa to investigate the potential impact of PrEP in averting new infections. The model utilizes age-structured mortality, fertility, partnership and condom use data to model the spread of HIV and the shift of peak prevalence to older age groups. The model shows that universal PrEP coverage would have to be impractically high to have a significant effect on incidence reduction while ART coverage expands. PrEP targeted to 15–35-year-old women would avert 10%–25% (resp. 13%–28%) of infections in this group and 5%–12% (resp. 7%–16%) of all infections in the period 2014–2025 if baseline incidence is 0.5% per year at 2025 (resp. 0.8% per year at 2025). The cost would be $12,500–$20,000 per infection averted, depending on the level of ART coverage and baseline incidence. An optimistic scenario of 30%–60% PrEP coverage, efficacy of at least 90%, no behavior change among PrEP users and ART coverage less than three times its 2010 levels is required to achieve this result. Targeting PrEP to 25–35-year-old women (at highest risk of infection) improves impact and cost-effectiveness marginally. Relatively low levels of condom substitution (e.g., 30%) do not nullify the efficacy of PrEP, but reduces cost-effectiveness by 35%–40%.

Conclusions/Significance

PrEP can avert as many as 30% of new infections in targeted age groups of women at highest risk of infection. The cost-effectiveness of PrEP relative to ART decreases rapidly as ART coverage increases beyond three times its coverage in 2010, after which the ART program would provide coverage to more than 65% of HIV₊ individuals. To have a high relative cost-effective impact on reducing infections in generalized epidemics, PrEP must utilize a window of opportunity until ART has been scaled up beyond this level.     

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

Background

Detection of acute HIV infection (AHI) with pooled nucleic acid amplification testing (NAAT) following HIV testing is feasible. However, cost-effectiveness analyses to guide policy around AHI screening are lacking; particularly after more sensitive third-generation antibody screening and rapid testing.

Methods and Findings

We conducted a cost-effectiveness analysis of pooled NAAT screening that assessed the prevention benefits of identification and notification of persons with AHI and cases averted compared with repeat antibody testing at different intervals. Effectiveness data were derived from a Centers for Disease Control and Prevention AHI study conducted in three settings: municipal sexually transmitted disease (STD) clinics, a community clinic serving a population of men who have sex with men, and HIV counseling and testing sites. Our analysis included a micro-costing study of NAAT and a mathematical model of HIV transmission. Cost-effectiveness ratios are reported as costs per quality-adjusted life year (QALY) gained in US dollars from the societal perspective. Sensitivity analyses were conducted on key variables, including AHI positivity rates, antibody testing frequency, symptomatic detection of AHI, and costs. Pooled NAAT for AHI screening following annual antibody testing had cost-effectiveness ratios exceeding US$200,000 per QALY gained for the municipal STD clinics and HIV counseling and testing sites and was cost saving for the community clinic. Cost-effectiveness ratios increased substantially if the antibody testing interval decreased to every 6 months and decreased to cost-saving if the testing interval increased to every 5 years. NAAT was cost saving in the community clinic in all situations. Results were particularly sensitive to AHI screening yield.

Conclusions

Pooled NAAT screening for AHI following negative third-generation antibody or rapid tests is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings. Please see later in the article for the Editors'' Summary     

Willingness to accept HIV pre-exposure prophylaxis among Chinese men who have sex with men

Objective

We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors.

Methods

This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis.

Results

A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13–0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14–0.67) were independently associated with willingness to accept PrEP.

Conclusions

The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community.     

The cost-effectiveness of tuberculosis preventive therapy for HIV-infected individuals in southern India: a trial-based analysis

Background

Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.

Methods

We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm³, and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).

Results

Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.

Conclusions

Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.     

Expanded HIV Testing in Low-Prevalence,High-Income Countries: A Cost-Effectiveness Analysis for the United Kingdom

Objective

In many high-income countries with low HIV prevalence, significant numbers of persons living with HIV (PLHIV) remain undiagnosed. Identification of PLHIV via HIV testing offers timely access to lifesaving antiretroviral therapy (ART) and decreases HIV transmission. We estimated the effectiveness and cost-effectiveness of HIV testing in the United Kingdom (UK), where 25% of PLHIV are estimated to be undiagnosed.

Design

We developed a dynamic compartmental model to analyze strategies to expand HIV testing and treatment in the UK, with particular focus on men who have sex with men (MSM), people who inject drugs (PWID), and individuals from HIV-endemic countries.

Methods

We estimated HIV prevalence, incidence, quality-adjusted life years (QALYs), and health care costs over 10 years, and cost-effectiveness.

Results

Annual HIV testing of all adults could avert 5% of new infections, even with no behavior change following HIV diagnosis because of earlier ART initiation, or up to 18% if risky behavior is halved. This strategy costs £67,000–£106,000/QALY gained. Providing annual testing only to MSM, PWID, and people from HIV-endemic countries, and one-time testing for all other adults, prevents 4–15% of infections, requires one-fourth as many tests to diagnose each PLHIV, and costs £17,500/QALY gained. Augmenting this program with increased ART access could add 145,000 QALYs to the population over 10 years, at £26,800/QALY gained.

Conclusions

Annual HIV testing of key populations in the UK is very cost-effective. Additional one-time testing of all other adults could identify the majority of undiagnosed PLHIV. These findings are potentially relevant to other low-prevalence, high-income countries.