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      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

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          Abstract

          Gabriela Gomez and colleagues developed a mathematical model of the HIV epidemic among men who have sex with men and transwomen in Lima, Peru to explore whether HIV pre-exposure prophylaxis could be a cost-effective addition to existing HIV prevention strategies.

          Abstract

          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

          Editors' Summary

          Background

          Without a vaccine, the only ways to halt the global HIV epidemic are prevention strategies that reduce transmission of the HIV virus. Up until recently, behavioral strategies such as condom use and reduction of sexual partners have been at the center of HIV prevention. In the past few years, several biological prevention measures have also been shown to be effective in reducing (though not completely preventing) HIV transmission. These include male circumcision, treatment for prevention (giving antiretroviral drugs to HIV-infected people, before they need it for their own health, to reduce their infectiousness) and pre-exposure prophylaxis (or PrEP), in which HIV-negative people use antiretroviral drugs to protect themselves from infection. One PrEP regimen (a daily pill containing two different antiretrovirals) has been shown in a clinical trial to reduce new infections by 44% in of men who have sex with men (MSM). In July 2012, the US Food and Drug Administration approved this PrEP regimen to reduce the risk of HIV infection in uninfected men and women who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. The approval makes it clear that PrEP needs to be used in combination with safe sex practices.

          Why Was This Study Done?

          Clinical trials have shown that PrEP can reduce HIV infections among participants, but they have not examined the consequences PrEP could have at the population level. Before decision-makers can decide whether to invest in PrEP programs, they need to know about the costs and benefits at the population level. Besides the price of the drug itself, the costs include HIV testing before starting PrEP, as well as regular tests thereafter. The health benefits of reducing new HIV infections are calculated in “disability-adjusted life years” (or DALYs) averted. One DALY is equal to one year of healthy life lost. Other benefits include future savings in lifelong HIV/AIDS treatment for every person whose infection is prevented by PrEP.

          This study estimates the potential costs and health benefits of several hypothetical PrEP roll-out scenarios among the community of MSM in Lima, Peru. The scientists chose this community because many of the participants in the clinical trial that showed that PrEP can reduce infections came from this community, and they therefore have some knowledge on how PrEP affects HIV infection rates and behavior in this population. Because the HIV epidemic in Lima is concentrated among MSM, similar to most of Latin America and several other developed countries, the results might also be relevant for the evaluation of PrEP in other places.

          What Did the Researchers Do and Find?

          For their scenarios, the researchers looked at “high coverage” and “low coverage” scenarios, in which 20% and 5% of uninfected individuals use PrEP, respectively. They also divided the MSM community into those at lower risk of becoming infected and those at higher risk. The latter group consisted of transwomen at higher risk (transsexuals and transvestites with many sexual partners) and male sex workers. In a “uniform coverage” scenario, PrEP is equally distributed among all MSM. “Prioritized scenarios” cover transwomen at higher risk and sex workers preferentially. Two additional important factors for the estimated benefits are treatment adherence (i.e., whether people take the pills they have been prescribed faithfully over long periods of time even though they are not sick) and changes in risk behavior (i.e., whether the perceived protection provided by PrEP leads to more unprotected sex).

          The cost estimates for PrEP included the costs of the drug itself and HIV tests prior to PrEP prescription and at three-month intervals thereafter, as well as outreach and counseling services and condom and lubricant promotion and provision.

          To judge whether under the various scenarios PrEP is cost-effective, the researchers applied two commonly used but different cost-effectiveness thresholds. The World Health Organization's WHO-CHOICE initiative considers an intervention cost-effective if its cost is less than three times the gross domestic product (GDP) per capita per DALY averted. For Peru, this means an intervention should cost less than US$16,302 per DALY. The World Bank has more stringent criteria: it considers an intervention cost-effective for a middle-income country like Peru if it costs less than US$500 per DALY averted.

          The researchers estimate that PrEP is cost-effective in Lima's MSM population for most scenarios by WHO-CHOICE guidelines. Only scenarios that prioritize PrEP to those most likely to become infected (i.e., transwomen at higher risk and sex workers) are cost-effective (and only barely) by the more stringent World Bank criteria. If the savings on antiretroviral drugs to treat people with HIV (those who would have become infected without PrEP) are included in the calculation, most scenarios become cost-effective, even under World Bank criteria.

          The most cost-effective scenario, namely, having a modest coverage of 5%, prioritizing PrEP to transwomen at higher risk and sex workers, and assuming fairly high adherence levels among PrEP recipients, is estimated to avert about 8% of new infections among this community over ten years.

          What Do these Findings Mean?

          These findings suggest that under some circumstances, PrEP could be a cost-effective tool to reduce new HIV infections. However, as the researchers discuss, PrEP is expensive and only partly effective. Moreover, its effectiveness depends on two behavioral factors—adherence to a strict drug regimen and continued practicing of safe sex—both of which remain hard to predict. As a consequence, PrEP alone is not a valid strategy to prevent new HIV infections. It needs instead to be considered as one of several available tools. If and when PrEP is chosen as part of an integrated prevention strategy will depend on the specific target population, the overall funds available, and how well its cost-effectiveness compares with other prevention measures.

          Additional Information

          Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001323.

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          Most cited references23

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          HIV and risk environment for injecting drug users: the past, present, and future.

          We systematically reviewed reports about determinants of HIV infection in injecting drug users from 2000 to 2009, classifying findings by type of environmental influence. We then modelled changes in risk environments in regions with severe HIV epidemics associated with injecting drug use. Of 94 studies identified, 25 intentionally examined risk environments. Modelling of HIV epidemics showed substantial heterogeneity in the number of HIV infections that are attributed to injecting drug use and unprotected sex. We estimate that, during 2010-15, HIV prevalence could be reduced by 41% in Odessa (Ukraine), 43% in Karachi (Pakistan), and 30% in Nairobi (Kenya) through a 60% reduction of the unmet need of programmes for opioid substitution, needle exchange, and antiretroviral therapy. Mitigation of patient transition to injecting drugs from non-injecting forms could avert a 98% increase in HIV infections in Karachi; whereas elimination of laws prohibiting opioid substitution with concomitant scale-up could prevent 14% of HIV infections in Nairobi. Optimisation of effectiveness and coverage of interventions is crucial for regions with rapidly growing epidemics. Delineation of environmental risk factors provides a crucial insight into HIV prevention. Evidence-informed, rights-based, combination interventions protecting IDUs' access to HIV prevention and treatment could substantially curtail HIV epidemics. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

            Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap. We analysed data on 12,574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. FINDINGS During 24,310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/microL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/microL, 0.52 (0.44-0.63) for 100-199 cells/microL, 0.24 (0.20-0.30) for 200-349 cells/microL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/microL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100,000 copies/microL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata. The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.
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              Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa.

              Mounting evidence has revealed pathological interactions between HIV and malaria in dually infected patients, but the public health implications of the interplay have remained unclear. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes; in addition, susceptibility to malaria is enhanced in HIV-infected patients. A mathematical model applied to a setting in Kenya with an adult population of roughly 200,000 estimated that, since 1980, the disease interaction may have been responsible for 8,500 excess HIV infections and 980,000 excess malaria episodes. Co-infection might also have facilitated the geographic expansion of malaria in areas where HIV prevalence is high. Hence, transient and repeated increases in HIV viral load resulting from recurrent co-infection with malaria may be an important factor in promoting the spread of HIV in sub-Saharan Africa.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                PLoS
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                October 2012
                October 2012
                9 October 2012
                : 9
                : 10
                : e1001323
                Affiliations
                [1 ]Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, United Kingdom
                [2 ]Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands
                [3 ]Instituto de Estudios en Salud, Sexualidad y Desarrollo Humano, Lima, Peru
                [4 ]Universidad Peruana Cayetano Heredia, Lima, Peru
                [5 ]Gladstone Institutes, University of California at San Francisco, San Francisco, California, United States of America
                Harvard School of Public Health, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GBG AB CFC ERS GPG TBH. Performed the experiments: AB GBG TBH. Analyzed the data: AB GBG TBH. Contributed reagents/materials/analysis tools: RMG CFC ERS. Wrote the first draft of the manuscript: GBG AB. Contributed to the writing of the manuscript: GBG AB CFC ERS RMG GPG TBH. ICMJE criteria for authorship read and met: GBG AB CFC ERS RMG GPG TBH. Agree with manuscript results and conclusions: GBG AB CFC ERS RMG GPG TBH. Developed the model: AB, with the support of TBH. Reviewed data and literature: GBG AB.

                Article
                PMEDICINE-D-11-01724
                10.1371/journal.pmed.1001323
                3467261
                23055836
                67220274-1b74-46ed-a697-07c9028f5751
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 July 2011
                : 24 August 2012
                Page count
                Pages: 15
                Funding
                This work was principally funded by the Bill & Melinda Gates Foundation. Additional funding: the Medical Research Council UK, The Wellcome Trust, US National Institutes of Health, and The Gladstone Institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Sexually Transmitted Diseases
                AIDS
                Infectious Disease Modeling
                Public Health
                Social and Behavioral Sciences
                Economics
                Health Economics
                Cost-Effectiveness Analysis

                Medicine
                Medicine

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