Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah
Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities. PMID:28250534
Naswa, Smriti; Marfatia, Y. S.
Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568
Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O
Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present
Full Text Available According to the Center for Disease Control and Prevention (CDC, there were 2.1 million new human immunodeficiency virus (HIV cases reported worldwide in 2015, which shows that siginificant work needs to be done to prevent the transmission of HIV. Research to date has focused mainly on high-risk men who have sex with men, but many women around the world are also at a high risk for HIV transmissions. In studies conducted, the incidence of HIV infection in high-risk individuals decreases over 90% when high-risk individuals use pre-exposure prophylaxis (PreP HIV, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC safely. Current data and studies on pre-exposure prophylaxis were discussed in this review.
Flash, Charlene A; Frost, Elizabeth L T; Giordano, Thomas P; Amico, K Rivet; Cully, Jeffrey A; Markham, Christine M
HIV pre-exposure prophylaxis has been proven to be an effective tool in HIV prevention. However, numerous barriers still exist in pre-exposure prophylaxis implementation. The framework of Intervention Mapping was used from August 2016 to October 2017 to describe the process of adoption, implementation, and maintenance of an HIV prevention program from 2012 through 2017 in Houston, Texas, that is nested within a county health system HIV clinic. Using the tasks outlined in the Intervention Mapping framework, potential program implementers were identified, outcomes and performance objectives established, matrices of change objectives created, and methods and practical applications formed. Results include the formation of three matrices that document program outcomes, change agents involved in the process, and the determinants needed to facilitate program adoption, implementation, and maintenance. Key features that facilitated successful program adoption and implementation were obtaining leadership buy-in, leveraging existing resources, systematic evaluation of operations, ongoing education for both clinical and nonclinical staff, and attention to emergent issues during launch. The utilization of Intervention Mapping to delineate the program planning steps can provide a model for pre-exposure prophylaxis implementation in other settings. Copyright © 2018. Published by Elsevier Inc.
Desai, Monica; Field, Nigel; Grant, Robert; McCormack, Sheena
Although pre-exposure prophylaxis (PrEP)-the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV-is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O
Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits
Kecojevic, Aleksandar; Basch, Corey; Basch, Charles; Kernan, William
Antiretroviral (ARV) medicines reduce the risk of transmitting the HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in combination with safer sex practices for HIV-negative individuals at a high risk for infection, but are underused in HIV prevention. Previous literature suggests that YouTube is extensively used to share health information. While pre-exposure prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is limited understanding of YouTube videos as a source of information on PrEP. The objective of this study was to describe the sources, characteristics, and content of the most widely viewed PrEP YouTube videos published up to October 1, 2016. The keywords "pre-exposure prophylaxis" and "Truvada" were used to find 217 videos with a view count >100. Videos were coded for source, view count, length, number of comments, and selected aspects of content. Videos were also assessed for the most likely target audience. The total cumulative number of views was >2.3 million, however, a single Centers for Disease Control and Prevention video accounted for >1.2 million of the total cumulative views. A great majority (181/217, 83.4%) of the videos promoted the use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas less than one third addressed the costs, side effects, and safety aspects relating to PrEP. Medical and academic institutions were the sources of the largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%), community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%). Videos uploaded by the media sources were more likely to discuss the cost of PrEP (PYouTube videos can be used to share reliable PrEP information with individuals. Further research is needed to identify the best practices for using this medium to promote and increase PrEP uptake. ©Aleksandar Kecojevic
Full Text Available Daisy Maria Machado,1 Alexandre Machado de Sant’Anna Carvalho,2 Rachel Riera3 1Disciplina de Infectologia Pediátrica, Departamento de Pediatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, 3Disciplina de Medicina Baseada em Evidências, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no
Hurt, Christopher B.; Eron, Joseph J.; Cohen, Myron S.
Prompted by 3 cases of resistance noted in the Pre-Exposure Prophylaxis Initiative and TDF2 trials, we examined literature on mutations elicited by antiretrovirals used for pre-exposure prophylaxis. We discuss signature mutations, how rapidly these emerge, and individual-level and public health consequences of antiretroviral resistance.
De Man, Jeroen; Colebunders, Robert; Florence, Eric; Laga, Marie; Kenyon, Christopher
New tools are needed to bring down ongoing high HIV incidence. This review aims to evaluate the place of one of these new tools (pre-exposure prophylaxis) in a comprehensive prevention strategy. Several trials have demonstrated the safety and the efficacy of pre-exposure prophylaxis in HIV prevention. Two large trials have, however, failed to show such efficacy. This was likely due to poor adherence in these trials. New forms of long-acting pre-exposure prophylaxis currently in trials may deal with these problems of low adherence. Pre-exposure prophylaxis has been demonstrated to be cost-effective within certain settings. The introduction of pre-exposure prophylaxis into prevention programs needs to be carefully thought through. For example, pre-exposure prophylaxis-induced risk compensation, at both an individual and population level, could undermine other aspects of a comprehensive HIV prevention program. In conclusion, pre-exposure prophylaxis could be a useful additional tool for the prevention of HIV in specific high-risk groups. It should be implemented in a way that deals with issues such as ensuring high adherence and ensuring that pre-exposure prophylaxis does not detract from, but complements, other more fundamental elements of HIV prevention programs.
Machado, Daisy Maria; de Sant’Anna Carvalho, Alexandre Machado; Riera, Rachel
Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years. PMID:29238237
Ayerdi-Aguirrebengoa, Oskar; Vera-García, Mar; Puerta-López, Teresa; Raposo-Utrilla, Montserrat; Rodríguez-Martín, Carmen; Del Romero-Guerrero, Jorge
HIV Pre-Exposure Prophylaxis (PrEP) consists of administering antiretroviral drugs to seronegative individuals with high risk practices. The aim of the study was to describe the characteristics of recent seroconverted HIV patients in order to determine the profile of the appropriate candidates for PrEP. A descriptive study of all patients diagnosed with HIV infection in 2014, and who had achieved a documented negative serology over the previous 12 months. A specific form was completed to determine the sociodemographic, behavioural, and clinical features, with complementary tests being performed for other sexually transmitted infections. Almost all (98.4%) of the 61 recent seroconverted were men who have sex with men, and aged between 20 to 39 years (88.5%). They also had a background of sexually transmitted infections (80.3%), performed multiple and unprotected sexual practices (82.7%), and under the effect of recreational drugs (87%). The evaluation of the risk factors for HIV infection in seronegative patients should enable the appropriate candidates for PrEP to be identified. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Ana Rita Diniz
Full Text Available Objectives: To review existing data on Pre-Exposure Prophylaxis (PrEP for prevention of HIV infection, including the role of medical male circumcision, oral administration of antiretroviral drugs and topical microbicides. Data Sources: PubMed and www.clinicaltrials.gov. Review Methods: Comprehensive review. Results: Medical male circumcision has been shown to prevent 48-60% of new HIV-1 infections. The efficacy rate of antiretroviral drugs given per os to prevent HIV infection varies in direct association with the adherence rate (62.2% in TDF2 study with 84% adherence; 44% in iPrEx study with <50% adherence; 48% in Bangkok study with 67% adherence; 67-75% in Partners PrEP study with 82% adherence; and 6% in FEM-PrEP study with 40% adherence. As for the use of topic microbicides, the CAPRISA 004 study showed 39% reduction in HIV infection using a 1% tenofovir gel. On the other hand, PRO2000 gel showed a modest reduction of 30% which was not statistically significant. Conclusions: The studies suggest that medical male circumcision is highly cost-effective at preventing HIV infection but requires careful communication strategies to be successful. PrEP using antiretroviral drugs is also very effective but it is highly dependent on the adherence rate. As for topical microbicides, 1% tenofovir gel is currently the only promising option.
Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid
Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641
Wood, Sarah M; Lee, Susan; Barg, Frances K; Castillo, Marne; Dowshen, Nadia
Our primary aim was to explore themes regarding attitudes toward HIV pre-exposure prophylaxis (PrEP) among young transgender women (YTW), in order to develop a theoretical model of PrEP uptake in this population disproportionally affected by HIV. Qualitative study nested within a mixed-method study characterizing barriers and facilitators to health services for YTW. Participants completed an in-depth interview exploring awareness of and attitudes toward PrEP. Key themes were identified using a grounded theory approach. Participants (n = 25) had a mean age of 21.2 years (standard deviation 2.2, range 17-24) and were predominately multiracial (36%) and of HIV-negative or unknown status (68%). Most participants (64%) reported prior knowledge of PrEP, and 28% reported current use or intent to use PrEP. Three major content themes that emerged were variability of PrEP awareness, barriers and facilitators to PrEP uptake, and emotional benefits of PrEP. Among participants without prior PrEP knowledge, participants reported frustration that PrEP information has not been widely disseminated to YTW, particularly by health care providers. Attitudes toward PrEP were overwhelmingly positive; however, concerns were raised regarding barriers including cost, stigma, and adherence challenges. Both HIV-positive and negative participants discussed emotional and relationship benefits of PrEP, which were felt to extend beyond HIV prevention alone. A high proportion of YTW in this study had prior knowledge of PrEP, and attitudes toward PrEP were positive among participants. Our findings suggest several domains to be further explored in PrEP implementation research, including methods of facilitating PrEP dissemination and emotional motivation for PrEP uptake. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
The advent of HIV pre-exposure prophylaxis (PrEP) as a HIV-prevention strategy has received optimistic support among HIV researchers. However, discourse on PrEP trials has tended to be dominated by the disputes arising between some activist groups and researchers about the research methodologies. Instead, this ...
Hankins, Catherine A.; Dybul, Mark R.
Public health experts are wrestling with how to translate recent scientific findings from pre-exposure prophylaxis (PrEP) effectiveness trials into real-world programmes. This review summarizes clinical trial findings on oral and topical PrEP, discusses how decision-makers can evaluate the place of
Hoornenborg, Elske; Krakower, Douglas S.; Prins, Maria; Mayer, Kenneth H.
: Pre-exposure prophylaxis (PrEP) is a potent and underutilized HIV prevention tool. In this paper we review the state of knowledge regarding PrEP implementation for men who have sex with men and transgender persons in early adopting countries. We focus on implementation of PrEP in demonstration
Seidman, Dominika L; Weber, Shannon; Cohan, Deborah
HIV prevention during pregnancy and lactation is critical for both maternal and child health. Pregnancy provides a critical opportunity for clinicians to elicit women's vulnerabilities to HIV and offer HIV testing, treatment and referral and/or comprehensive HIV prevention options for the current pregnancy, the postpartum period and safer conception options for future pregnancies. In this commentary, we review the safety of oral pre-exposure prophylaxis with tenofovir/emtricitabine in pregnant and lactating women and suggest opportunities to identify pregnant and postpartum women at substantial risk of HIV. We then describe a clinical approach to caring for women who both choose and decline pre-exposure prophylaxis during pregnancy and postpartum, highlighting areas for future research. Evidence suggests that pre-exposure prophylaxis with tenofovir/emtricitabine is safe in pregnancy and lactation. Identifying women vulnerable to HIV and eligible for pre-exposure prophylaxis is challenging in light of the myriad of individual, community, and structural forces impacting HIV acquisition. Validated risk calculators exist for specific populations but have not been used to screen and offer HIV prevention methods. Partner testing and engagement of men living with HIV are additional means of reaching at-risk women. However, women's vulnerabilities to HIV change over time. Combining screening for HIV vulnerability with HIV and/or STI testing at standard intervals during pregnancy is a practical way to prompt providers to incorporate HIV screening and prevention counselling. We suggest using shared decision-making to offer women pre-exposure prophylaxis as one of multiple HIV prevention strategies during pregnancy and postpartum, facilitating open conversations about HIV vulnerabilities, preferences about HIV prevention strategies, and choosing a method that best meets the needs of each woman. Growing evidence suggests that pre-exposure prophylaxis with tenofovir
Jaspal, Rusi; Nerlich, Brigitte
Pre-exposure prophylaxis is a novel biomedical HIV prevention option for individuals at high risk of HIV acquisition. Although pre-exposure prophylaxis has yielded encouraging results in various clinical trials, opponents argue that pre-exposure prophylaxis poses a number of risks to human health and to sexually transmitted infection prevention efforts. Using qualitative thematic analysis and social representation theory, this article explores coverage of pre-exposure prophylaxis in the UK print media between 2008 and 2015 in order to chart the emerging social representations of this novel HIV prevention strategy. The analysis revealed two competing social representations of pre-exposure prophylaxis: (1) as a positive development in the 'battle' against HIV (the hope representation) and (2) as a medical, social and psychological setback in this battle, particularly for gay/bisexual men (the risk representation). These social representations map onto the themes of pre-exposure prophylaxis as a superlatively positive development; pre-exposure prophylaxis as a weapon in the battle against HIV/AIDS; and risk, uncertainty and fear in relation to pre-exposure prophylaxis. The hope representation focuses on taking (individual and collective) responsibility, while the risk representation focuses on attributing (individual and collective) blame. The implications for policy and practice are discussed.
Pre-exposure prophylaxis (PrEP), in combination with traditional prevention strategies (such as condom use, voluntary HIV counseling and testing, and treatment for sexually transmitted infections), has been shown to effectively prevent HIV infection. As of September 2015, the World Health Organization recommends that people at substantial risk of HIV infection should be offered PrEP as an additional prevention choice, as part of comprehensive prevention. This article introduces how to apply a systematic review using the methodology of Grading of Recommendations Assessment, Development and Evaluation (GRADE) to write clinical guidelines. With support from the Taiwan Centers for Disease Control, the Taiwan AIDS Society published clinical guidelines for oral pre-exposure prophylaxis in Taiwan. Nurses are responsible to apply evidence-based knowledge and to use their professional influence to shape health policies related to HIV prevention.
Mugwanya, Kenneth K; Baeten, Jared M
Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.
Paul W Denton
Full Text Available Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection.We show that the female reproductive tract of humanized bone marrow-liver-thymus (BLT mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT that closely mimics what is observed in HIV-1-infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8 of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5 given pre-exposure prophylaxis of emtricitabine (FTC/tenofovir disoproxil fumarate (TDF showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006.The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.
Yoong, Deborah; Naccarato, Mark; Sharma, Malika; Wilton, James; Senn, Heather; Tan, Darrell Hs
Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted. © The Author(s) 2015.
Hurt, Christopher B; Eron, Joseph J; Cohen, Myron S
Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)-uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx). These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials. Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men. A similar case in the TDF2 study resulted in resistance to both ARVs. These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP. Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance.
Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna
People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.
Santiago Moreno Guillen
Full Text Available Despite the global stabilization of the number of new HIV infections in recent years, there has been an increase in new infections among men who have sex with men. This fact indicates the lack of effectiveness of the measures and prevention campaigns established so far for this group. It is therefore necessary to implement alternative preventive measures for them. Pre-exposure pharmacological prophylaxis (PrEP is one of the best evaluated options and has had high protection rates in both clinical and real-life trials. The strategy has also shown an adequate profile in terms of safety, tolerance, adverse effects and cost-effectiveness in the studies carried out to assess this important topic.
There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting. PMID:20624303
Queiroz, Artur Acelino Francisco Luz Nunes; Sousa, Alvaro Francisco Lopes de
This study aimed to identify health-promoting contents focused on HIV/Aids prevention in messages posted in a Facebook group for debates on the use of pre-exposure prophylaxis (PrEP). This was a prospective observational study using systematic non-participant observation. From July 2015 to June 2016, all the posts in the group were catalogued and formed a corpus. Everything was processed in IRaMuTeQ and analyzed by descending hierarchical classification. The collected data were grouped in three classes: (1) HIV/Aids prevention: discussing prophylaxis, treatment, target public, and side effects; (2) universal access to PrEP in Brazil: discussing government responsibilities; (3) on-line purchase of truvada: exposing a situation of vulnerability. The findings call attention to a potential public health problem and provide backing for understanding facilitators and barriers to the use of PrEP in Brazil through the identification of health-promoting content linked to individual, social, and institutional markers.
D.C.J. Vissers (Debby); H.A.C.M. Voeten (Hélène); N.J.D. Nagelkerke (Nico); J.D.F. Habbema (Dik); S.J. de Vlas (Sake)
textabstractBackground: Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV
Wheelock, Ana; Eisingerich, Andreas B.; Gomez, Gabriela B.; Gray, Emily; Dybul, Mark R.; Piot, Peter
To examine policymakers and providers' views on pre-exposure prophylaxis (PrEP) and their willingness to support its introduction, to inform policy and practice in this emerging field. Semistructured qualitative interview study. Peru, Ukraine, India, Kenya, Uganda, Botswana and South Africa. 35
Hankins, Catherine A.
Clinical trials of HIV pre-exposure prophylaxis (PrEP) antiretroviral drugs have shown excellent protection against HIV acquisition when plasma drug levels are detectable, indicating good adherence. Cost-effectiveness depends on epidemic context, adherence, drug cost, and other factors. For
Maljaars, Lennart P.; Gill, Katherine; Smith, Philip J.; Gray, Glenda E.; Dietrich, Janan J.; Gomez, Gabriela B.; Bekker, Linda-Gail
Background: Approximately 3 million adolescents and young adults (AYA), between the ages of 15 years and 24 years, are living with HIV in sub-Saharan Africa. The use of pre-exposure prophylaxis (PrEP) may be a promising HIV prevention tool to bridge the high-risk years of AYA between sexual debut
Nadery, S.; Geerlings, S. E.
The global incidence of human immunodeficiency virus (HIV) infection has decreased by 15% over the past years, but is still too high. Despite current programs to reduce the incidence of HIV infection, further approaches are needed to limit this epidemic. Oral antiretroviral pre-exposure prophylaxis
Glidden, David; Grant, Robert; Mulligan, Kathleen; Solomon, MM; Lama, JR; Glidden, DV; McMahan, V; Liu, AY; Vicente, J; Veloso, VG; Mayer, KH; Chariyalertsak, S
Objective: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. Design and methods: The Iniciativa Profilaxis Pre-Exposición (iP
Fruhauf, Timothee; Coleman, Jenell S
To estimate the proportion of women at increased risk of sexual human immunodeficiency virus (HIV) acquisition during pregnancy in a high HIV incidence urban setting to identify those who may be eligible for pre-exposure prophylaxis. We conducted a retrospective cohort study of women who received prenatal care at a large academic center in 2012. Univariable analyses and multiple logistic regression models were built to identify correlates for pre-exposure prophylaxis eligibility. Among 1,637 pregnant women, mean age was 27.6 years (SD 6.3), 59.7% were African American, and 56.0% were single. Based on the Centers for Disease Control and Prevention's guidelines, more than 10% of women were at increased risk for HIV acquisition during pregnancy and eligible for pre-exposure prophylaxis. Younger [adjusted odds ratio (OR) 0.9/1-year increase, 95% CI 0.8-0.9], single (adjusted OR 2.4, 95% CI 1.2-4.8), African American women (adjusted OR 3.3, 95% CI 1.6-6.7) with higher parity (adjusted OR 1.3/one-child increase, 95% CI 1.1-1.5), and who smoked regularly during pregnancy (adjusted OR 1.8, 95% CI 1.0-3.0) had greater odds of being eligible for pre-exposure prophylaxis at any time during pregnancy. Pregnancy is a vulnerable period during which some heterosexual women in urban settings have a high risk for HIV acquisition and stand to benefit from pre-exposure prophylaxis.
Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo
Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.
Patel, Rupa R; Mena, Leandro; Nunn, Amy; McBride, Timothy; Harrison, Laura C; Oldenburg, Catherine E; Liu, Jingxia; Mayer, Kenneth H; Chan, Philip A
Pre-exposure prophylaxis (PrEP) can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island) from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%), 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003). Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.
Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A
Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.
Rupa R Patel
Full Text Available Pre-exposure prophylaxis (PrEP can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%, 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003. Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.
Edelman, E Jennifer; Moore, Brent A; Calabrese, Sarah K; Berkenblit, Gail; Cunningham, Chinazo; Patel, Viraj; Phillips, Karran; Tetrault, Jeanette M; Shah, Minesh; Fiellin, David A; Blackstock, Oni
Pre-exposure prophylaxis for HIV (PrEP) is recommended for people who inject drugs (PWID). Despite their central role in disease prevention, willingness to prescribe PrEP to PWID among primary care physicians (PCPs) is largely understudied. We conducted an online survey (April-May 2015) of members of a society for academic general internists regarding PrEP. Among 250 respondents, 74% (n = 185) of PCPs reported high willingness to prescribe PrEP to PWID. PCPs were more likely to report high willingness to prescribe PrEP to all other HIV risk groups (p's < 0.03 for all pair comparisons). Compared with PCPs delivering care to more HIV-infected clinic patients, PCPs delivering care to fewer HIV-infected patients were more likely to report low willingness to prescribe PrEP to PWID (Odds Ratio [95% CI] = 6.38 [1.48-27.47]). PCP and practice characteristics were not otherwise associated with low willingness to prescribe PrEP to PWID. Interventions to improve PCPs' willingness to prescribe PrEP to PWID are needed.
Haberer, Jessica E.; Bangsberg, David R.; Baeten, Jared M.; Curran, Kathryn; Koechlin, Florence; Amico, K. Rivet; Anderson, Peter; Mugo, Nelly; Venter, Francois; Goicochea, Pedro; Caceres, Carlos; O’Reilly, Kevin
Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention. PMID:26103095
Mugwanya, Kenneth K; Donnell, Deborah; Celum, Connie; Thomas, Katherine K; Ndase, Patrick; Mugo, Nelly; Katabira, Elly; Ngure, Kenneth; Baeten, Jared M
Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour. We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex-unprotected by a condom-during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour. We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011. Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk
DiStefano, Anthony S; Takeda, Makiko
Biomedical HIV prevention strategies are playing an increasingly prominent role in addressing HIV epidemics globally, but little is known about their use in Japan, where persistent HIV disparities and a recently stable, but not declining, national epidemic indicate the need for evolving approaches. We conducted an ethnographic study to determine the context of pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) use and to identify directions for future research and action in Japan. We used data from observational fieldwork in the Kansai region and Tokyo Metropolitan Area (n = 178 persons observed), qualitative interviews (n = 32), documents and web-based data sources (n = 321), and email correspondences (n = 9) in the period 2013-2016. Drug approvals by Japan's regulatory agencies, insurance coverage for medications, and policies by healthcare institutions and government agencies were the main factors affecting PrEP and PEP legality, use, and awareness. Awareness and the observable presence of PrEP and PEP were very limited, particularly at the community level. PrEP and PEP held appeal for Japanese scientists and activists, and for study participants who represented various other stakeholder groups; however, significant concerns prevented open endorsements. Japanese health officials should prioritize a national discussion, weigh empirical evidence, and strongly consider formal approval of antiretroviral (ARV) medications for use in PrEP and both occupational and nonoccupational PEP. Once approved, social marketing campaigns can be used to advertise widely and increase awareness. Future research would benefit from theoretical grounding in a diffusion of innovations framework. These findings can inform current and future ARV-based prevention strategies at a critical time in the international conversation.
Grant, Jenna M
Controversies about global clinical trials, particularly HIV trials, tend to be framed in terms of ethics. In this article, I explore debates about ethics in the Cambodia Pre-Exposure Prophylaxis trial, which was designed to test the safety and efficacy of tenofovir as a prevention for HIV infection. Bringing together studies of public participation in science with studies of bioethics, I show how activists around the Cambodian Pre-Exposure Prophylaxis trial circulated and provoked debates about standards of research ethics, as opposed to research methodology. This postcolonial bioethics was configured through the circulation of and debate about ethics guidelines, and historically and culturally specific relations of vulnerability and responsibility between foreigners and Cambodians and between Cambodian leaders and Cambodian subjects. I argue that this shift in the object of ethical concern, from the experimental human subject to the relation between subjects and researchers, illustrates how a postcolonial field of articulation reformulates classical bioethics.
Hakre, Shilpa; Blaylock, Jason M; Dawson, Peter; Beckett, Charmagne; Garges, Eric C; Michael, Nelson L; Danaher, Patrick J; Scott, Paul T; Okulicz, Jason F
Abstract Providers are central to effective implementation of HIV pre-exposure prophylaxis (PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in the US Air Force (USAF) participated in a cross-sectional survey regarding knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated with PrEP knowledge were assessed in univariate and multivariate analyses. Among 403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed PrEP. In univar...
Lusti-Narasimhan, Manjula; Khosla, Rajat; Baggaley, Rachel; Temmerman, Marleen; McGrory, Elizabeth; Farley, Tim
Introduction: Two new microbicide products based on topical (vaginal) application of antiretroviral drugs – 1% tenofovir gel and the dapivirine ring – are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Discussion: Given that these new topical ...
Sullivan, Kristen A; Lyerly, Anne D
Though many women in need of access to HIV preventive regimes are pregnant, there is a dearth of data to guide these care decisions. While oral pre-exposure prophylaxis (PrEP) has been shown to prevent HIV infection in numerous high-risk populations, pregnant women have been excluded from all major prospective trials. We propose for ethical examination a theoretical trial-a prospective, observational study of PrEP for pregnant women at risk for HIV in sub-Saharan Africa-highlighting an ethical tradeoff that characterizes issues faced for advancing research in pregnancy. On the one hand, an "opportunistic" study design has certain ethical advantages: as formally construed, the research activity usually begins after decisions to use PrEP during pregnancy are made in the clinical setting. This minimizes research risks and avoids ethical problems that a randomized controlled trial (RCT) comparing PrEP to placebo would entail, particularly withholding care proven beneficial in other populations. On the other hand, observational studies yield less precise information than RCTs. This raises a broader question about the pace of research with pregnant women, as it typically takes many years after a drug's approval for use in the general population to determine safety of the medication in pregnancy. Such delays can have the effect of making it impossible to ethically conduct an RCT with pregnant women, reducing the likelihood that the research community is able to obtain robust, pregnancy-specific evidence. While an observational cohort is potentially the most ethically and scientifically justified research design to study PrEP in pregnancy, earlier involvement of pregnant women in studies of newer preventives may lead to evidence that is more timely and robust.
Raifman, Julia R.G.; Flynn, Colin; German, Danielle
Introduction Pre-exposure prophylaxis (PrEP) safely and effectively prevents HIV in populations at high risk, including men who have sex with men (MSM). PrEP scale-up depends upon primary care providers and community-based organizations (CBOs) sharing PrEP information. This study aimed to determine whether healthcare provider or CBO contact was associated with PrEP awareness among Baltimore MSM. Methods This study used 2014 Baltimore MSM National HIV Behavioral Surveillance data, which included data on health care, HIV and sexually transmitted infection testing, and receipt of condoms from CBOs. In 2015, associations were estimated between healthcare contacts and PrEP awareness through logistic regression models controlling for age, race, and education and clustering by venue. Comparative analyses were conducted with HIV testing as outcome. Results There were 401 HIV-negative participants, of whom 168 (42%) were aware of PrEP. Visiting a healthcare provider in the past 12 months, receiving an HIV test from a provider, and having a sexually transmitted infection test in the past 12 months were not significantly associated with PrEP awareness. PrEP awareness was associated with being out to a healthcare provider (OR = 2.97, 95% CI=1.78, 4.96, p<0.001); being tested for HIV (OR=1.50, 95% CI = 1.06, 2.13, p = 0.023); and receiving condoms from an HIV/AIDS CBO (OR = 2.59, 95% CI = 1.43, 4.64, p = 0.001). By contrast, HIV testing was significantly associated with most forms of healthcare contact. Conclusions PrEP awareness is not associated with most forms of healthcare contact, highlighting the need for guidelines and trainings to support provider discussion of PrEP with MSM. PMID:27662698
Li, Shuming; Li, Dongliang; Zhang, Lifen; Fan, Wensheng; Yang, Xueying; Yu, Mingrun; Xiao, Dong; Yan, Li; Zhang, Zheng; Shi, Wei; Luo, Fengji; Ruan, Yuhua; Jin, Qi
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. PMID:22479320
McNicholl, Janet M
Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.
Erin C Wilson
Full Text Available Safe and effective HIV prevention strategies are needed for transwomen. Transwomen in the US have a 34 times greater odds of being infected with HIV than all adults age 15-49, and in San Francisco, California 42.4% of transwomen are estimated to be infected with HIV. Pre-exposure prophylaxis (PrEP is the first biomedical intervention with promise for reducing HIV acquisition in transwomen. However, little is known about whether transwomen know about PrEP, are taking PrEP and would be good candidates for PrEP based on their risk profile and behaviors. A population-based dataset was analyzed to determine how many transwomen in San Francisco knew about PrEP by the end of 2013 - more than a year after iPrex results demonstrated efficacy of PrEP in preventing HIV. We found that of 233 transwomen, only 13.7% had heard of PrEP. Transwomen who were living with HIV compared to those who were HIV-negative, and those who recently injected drugs compared to non-injection drug users were more likely to have heard of PrEP. Based on CDC guidelines for PrEP among MSM and IDU, 45 (30.2% transwomen of the 149 HIV-negative transwomen in the sample were candidates for PrEP. This estimate based on CDC criteria is arguably low. Given that almost half of transwomen in San Francisco are living with HIV, this findings points to a need for further consideration of PrEP criteria that are specific and tailored to the risks for HIV faced by transwomen that are different from MSM and injection drug users. Research to scale up access and test the effectiveness of PrEP for transwomen is also urgently needed.
Kai J. Jonas
Full Text Available Pre-exposure prophylaxis (PrEP with tenofovir disoproxil fumarate in combination with emtricitabine (FTC is a highly effective form of HIV prevention. Endeavors of health-care providers and activists in many countries over the world are directed at making access to PrEP possible, or increasing PrEP use among men-who-have-sex-with-men (MSM. We argue while this effort is necessary, we also need to consider modes of HIV prevention after a period of PrEP use. PrEP uptake is not a one-way street, meaning that individuals may discontinue PrEP use, either voluntarily and involuntarily. Voluntary discontinued PrEP use in conjunction with decreased or no HIV risk exposure is unproblematic, but involuntary discontinuations with continuous high level of HIV risk exposure calls for tailored post-PrEP use HIV prevention. We present a case study of an MSM individual who discontinued PrEP for medical reasons (renal function and seroconverted soon afterward, to illustrate the need for tailored HIV prevention post-PrEP. Furthermore, we provide additional contexts of PrEP discontinuation leading to populations that are in need for post-PrEP types of HIV prevention. Subsequently, we present suggestions for modes of post-PrEP HIV prevention based on knowledge–communication–choice model. Community organization and health-care providers should consider and prepare their HIV prevention consulting protocols for such types of clients and add post-PrEP HIV prevention measures to their consulting offer.
Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J
The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel
Full Text Available 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.
Full Text Available Men who have sex with men (MSM are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood.We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1 the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs; and 2 PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds.When PrEP drug costs were reduced by 60% (with no sexual disinhibition to 80% (assuming 25% sexual disinhibition, PrEP was cost-effective (at <$100,000 per QALY averted in all scenarios of base-case or better adherence, as long as the background HIV prevalence was greater than 10%. For PrEP to be cost saving at base-case adherence/efficacy levels and at a background prevalence of 20%, drug cost would need to be reduced to $8,021 per year with no disinhibition, and to $2,548 with disinhibition.Results from our analysis suggest that PrEP drug costs need to be reduced in order to be cost-effective across a range of background HIV prevalence. Moreover, our results provide guidance on the pricing of generic emtricitabine/tenofovir disoproxil fumarate, in order to provide those at high risk for HIV an affordable prevention option without financial burden on individuals or jurisdictions scaling-up coverage.
Madeline C Montgomery
Full Text Available The HIV epidemic in the United States (US disproportionately affects gay, bisexual, and other men who have sex with men (MSM. Pre-exposure prophylaxis (PrEP using co-formulated tenofovir disoproxil fumarate (TDF and emtricitabine (FTC has demonstrated high efficacy in reducing HIV incidence among MSM. However, low adherence was reported in major efficacy trials and may present a substantial barrier to successful PrEP implementation. Rates of adherence to PrEP in "real-world" clinical settings in the US remain largely unknown.We reviewed demographic and clinical data for the first 50 patients to enroll in a clinical PrEP program in Providence, Rhode Island. We analyzed self-reported drug adherence as well as drug concentrations in dried blood spots (DBS from patients who attended either a three- or six-month follow-up appointment. We further assessed drug concentrations and the resistance profile of a single patient who seroconverted while taking PrEP.Of the first 50 patients to be prescribed PrEP, 62% attended a follow-up appointment at three months and 38% at six months. Of those who attended an appointment at either time point (70%, n = 35, 92% and 95% reported taking ±4 doses/week at three and six months, respectively. Drug concentrations were performed on a random sample of 20 of the 35 patients who attended a follow-up appointment. TDF levels consistent with ±4 doses/week were found in 90% of these patients. There was a significant correlation between self-reported adherence and drug concentrations (r = 0.49, p = 0.02. One patient who had been prescribed PrEP seroconverted at his three-month follow-up visit. The patient's drug concentrations were consistent with daily dosing. Population sequencing and ultrasensitive allele-specific PCR detected the M184V mutation, but no other TDF- or FTC-associated mutations, including those present as minor variants.In this clinical PrEP program, adherence was high, and self-reported drug adherence
Zou, Yunfeng; Yang, Xiaobo; Abdullah, Abu S.; Zhong, Xiaoni; Ruan, Yuhua; Lin, Xinqin; Li, Mingqiang; Wu, Deren; Jiang, Junjun; Xie, Peiyan; Huang, Jiegang; Liang, Bingyu; Zhou, Bo; Su, Jinming; Liang, Hao; Huang, Ailong
Objectives Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. Methods A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. Results Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. Conclusions Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi. PMID:24465956
Montgomery, Madeline C; Oldenburg, Catherine E; Nunn, Amy S; Mena, Leandro; Anderson, Peter; Liegler, Teri; Mayer, Kenneth H; Patel, Rupa; Almonte, Alexi; Chan, Philip A
The HIV epidemic in the United States (US) disproportionately affects gay, bisexual, and other men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) using co-formulated tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has demonstrated high efficacy in reducing HIV incidence among MSM. However, low adherence was reported in major efficacy trials and may present a substantial barrier to successful PrEP implementation. Rates of adherence to PrEP in "real-world" clinical settings in the US remain largely unknown. We reviewed demographic and clinical data for the first 50 patients to enroll in a clinical PrEP program in Providence, Rhode Island. We analyzed self-reported drug adherence as well as drug concentrations in dried blood spots (DBS) from patients who attended either a three- or six-month follow-up appointment. We further assessed drug concentrations and the resistance profile of a single patient who seroconverted while taking PrEP. Of the first 50 patients to be prescribed PrEP, 62% attended a follow-up appointment at three months and 38% at six months. Of those who attended an appointment at either time point (70%, n = 35), 92% and 95% reported taking ±4 doses/week at three and six months, respectively. Drug concentrations were performed on a random sample of 20 of the 35 patients who attended a follow-up appointment. TDF levels consistent with ±4 doses/week were found in 90% of these patients. There was a significant correlation between self-reported adherence and drug concentrations (r = 0.49, p = 0.02). One patient who had been prescribed PrEP seroconverted at his three-month follow-up visit. The patient's drug concentrations were consistent with daily dosing. Population sequencing and ultrasensitive allele-specific PCR detected the M184V mutation, but no other TDF- or FTC-associated mutations, including those present as minor variants. In this clinical PrEP program, adherence was high, and self-reported drug adherence accurately
Javier Sánchez-Rubio Ferrández
Full Text Available Objective: To determine the level of support, knowledge and perceptions of pre-exposure prophylaxis (PrEP by Infectious Disease Specialists and Hospital Pharmacists in Spain. Methods: Cross-sectional study through an on-line 31-item survey (sociodemographical data, employment status/experience, knowledge of PrEP, use, identified barriers and economic issues. A univariate analysis was performed to evaluate the variables associated with support for PrEP, and compare the assessments by Specialists and Pharmacists. The questions about support for PrEP and agreement with the indication approval were repeated after showing data from published studies. The significance of the change in the answers was analyzed using the McNemar Test. Results: 211 questionnaires were received (80.1% from Pharmacists. 40.3% had low/no familiarity with PrEP (46.2% Pharmacists vs. 16.7% Physicians; p < 0.01. A 53.6% of them would support the use of PrEP (49.7% Pharmacists vs. 69% Physicians; p = 0.038. The minimum acceptable efficacy in order to support PrEP was 85.0 ± 15.5% (82.6 ± 12.1% by Physicians vs. 85.6 ± 15.0% by Pharmacists; p = 0.02. The variables associated with support were: medical profession (OR = 2.26; 95%CI 1.1-4.6; p = 0.038 and lower demand for efficacy (difference = 10.5%; 95%CI 6.9 to 14.1; p < 0.001. After receiving the information, there was an increase in their support for use and indication approval. Most participants (81.5% did not support its reimbursement. The main barriers identified were: an increase in risk behaviour (24.1%, increase in sexually transmitted diseases (19.0%, resistance (16.6% and cost (16.0%. Conclusions: More than half of participants were familiar with PrEP. The majority of them would support its use and the approval of the indication, but would not reimburse it. The use of PrEP in real practice is currently low.
Burns, David N; Grossman, Cynthia; Turpin, Jim; Elharrar, Vanessa; Veronese, Fulvia
Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (Truvada®) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research.
Kurtz, Steven P.; Buttram, Mance E.
Abstract Purpose: Street markets in antiretroviral medications for HIV have been documented, but sources of demand are not well understood. We report unexpected findings from qualitative research suggesting that some demand is for informal pre-exposure prophylaxis (PrEP). Methods: Focus groups with young men who have sex with men (N?=?31) yielded information on their understanding and use of PrEP. Results: Of those who had heard of it, few understood PrEP to be a physician-prescribed regimen;...
HIV pre-exposure prophylaxis (PrEP) has been introduced as another biomedical tool in HIV prevention. Whereas other such tools-including post-exposure prophylaxis (PEP) and interruption of perinatal transmission-have been embraced by those impacted by HIV, PrEP has been met with more conflict, especially within the gay community and HIV organizations. The "PrEP whore" has come to designate the social value and personal practices of those taking PrEP. This study examines the "PrEP whore" discourse by using queer theory and quare theory. Within these theoretical vantage points, the study explicates four discursive areas: slut shaming, dirty/clean binaries, mourning the loss of condoms, and reclaiming the inner whore. The study illuminates possible discursive strategies that lie outside of the domains of public health and within the individual and community.
Full Text Available Respiratory syncytial virus (RSV is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP of RSV infection in children at high risk. We found that maleic anhydride (ML-modified human serum albumin (HSA, designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.
Bond, Keosha T.; Gunn, Alana J.
Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug. PMID:28725660
To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N
Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.
Herron, Patrick D
Identifying sources of and eliminating social stigma associated with the promotion and use of pre-exposure prophylaxis (PrEP) for the prevention of sexually acquired HIV infection among men who have sex with men (MSM) is both a moral imperative and necessary requirement to ensure that public health objectives of HIV prevention can be met. This article will examine and address ethical concerns and criticisms regarding the use of PrEP, barriers to its promotion, and use among MSM and examine the types of social stigma associated with PrEP. An ethical justification for both healthcare and LGBT communities to address and overcome social stigma regarding the use of PrEP among MSM is offered.
Kurtz, Steven P; Buttram, Mance E
Street markets in antiretroviral medications for HIV have been documented, but sources of demand are not well understood. We report unexpected findings from qualitative research suggesting that some demand is for informal pre-exposure prophylaxis (PrEP). Focus groups with young men who have sex with men (N = 31) yielded information on their understanding and use of PrEP. Of those who had heard of it, few understood PrEP to be a physician-prescribed regimen; most believed it to be a pill taken before and/or after sex and acquired on the street or through HIV-positive friends. Implications for PrEP rollout and public health policy are discussed.
Solomon, Marc M; Lama, Javier R; Glidden, David V; Mulligan, Kathleen; McMahan, Vanessa; Liu, Albert Y; Guanira, Juan Vicente; Veloso, Valdilea G; Mayer, Kenneth H; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper Georges; Burns, David N; Grant, Robert M
Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.
Venter, Francois; Allais, Lucy; Richter, Marlise
The last few years have seen dramatic progress in the development of HIV pre-exposure prophylaxis (PrEP). These developments have been met by ethical concerns. HIV interventions are often thought to be ethically difficult. In a context which includes disagreements over human rights, controversies over testing policies, and questions about sexual morality and individual responsibility, PrEP has been seen as an ethically complex intervention. We argue that this is mistaken, and that in fact, PrEP does not raise new ethical concerns. Some of the questions posed by PrEP are not specific to HIV prophylaxis, but simply standard public health considerations about resource allocation and striking a balance between individual benefit and public good. We consider sexual disinhibition in the context of private prescriptions, and conclude that only unjustified AIDS-exceptionalism or inappropriate moralism about sex supports thinking that PrEP raises new ethical problems. This negative conclusion is significant in a context where supposed ethical concerns about PrEP have been raised, and in the context of HIV exceptionalism. © 2013 John Wiley & Sons Ltd.
Grant, Robert M; Smith, Dawn K
Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.
Gomez, Gabriela B.; Borquez, Annick; Caceres, Carlos F.; Segura, Eddy R.; Grant, Robert M.; Garnett, Geoff P.; Hallett, Timothy B.
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
Bil, Janneke P; Hoornenborg, Elske; Prins, Maria; Hogewoning, Arjan; Dias Goncalves Lima, Fernando; de Vries, Henry J C; Davidovich, Udi
Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP
Full Text Available BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP for prevention of HIV infection. The cost effectiveness of ‘on demand’ PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated.
Hoornenborg, Elske; Prins, Maria; Achterbergh, Roel C A; Woittiez, Lycke R; Cornelissen, Marion; Jurriaans, Suzanne; Kootstra, Neeltje A; Anderson, Peter L; Reiss, Peter; de Vries, Henry J C; Prins, Jan M; de Bree, Godelieve J
Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate
Nichols, B.E.; Boucher, C.A.B.; van Dijk, J.H.; Thuma, P.E.; Nouwen, J.L.; Baltussen, R.; van de Wijgert, J.; Sloot, P.M.A.; van de Vijver, D.A.M.C.
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
Bil, Janneke P.; Hoornenborg, Elske; Prins, Maria; Hogewoning, Arjan; Dias Goncalves Lima, Fernando; de Vries, Henry J. C.; Davidovich, Udi
Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP
Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi
Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use
Full Text Available Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5% were confirmed HIV-infected, 10 (2.2% HIV-uninfected, and one (0.2% had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days than participants receiving placebo (16.8 days (p = 0.02 and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04.The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106.
Hill, Brandon J; Bak, Trevor; VandeVusse, Alicia; Rosentel, Kris
This study describes the self-reported use of pre-exposure prophylaxis (PrEP) in the personal advertisements of men seeking sex with men in the United States on the online classified advertisement site, Craigslist. Overall self-reported PrEP use was low (0.20%; 95% confidence interval (CI)=0.18-0.22). However, PrEP use in personal ads was described in conjunction with seeking sexual risk behaviours including 'bareback' sex (22.7%; 95% CI=17.7-27.7%) and sex with substance use (26.8%; 95% CI=21.5-32.1%). Only 4.0% of personal ads sought safe sex (3.3%; 95% CI=1.2-5.4%) or required condoms (0.7%; 95% CI=-0.3-1.7%). Our findings underscore the need for increased public PrEP awareness, particularly among men seeking sex with men, as well as the importance of healthcare providers emphasising sexually transmissible infection prevention behaviours (i.e. condom use) used in conjunction with PrEP.
Bailey, Theodore C.; Sugarman, Jeremy
The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297
The global scale-up of AIDS treatment initiatives during the first decade of the twenty-first century has been referred to as a kind of 'pharmaceuticalisation' of public health, a trend that is now building in the area of HIV prevention. This paper traces the emergence and increased uptake of pre-exposure prophylaxis (PrEP), antiretroviral medications that can keep HIV negative individuals from becoming infected, placing it within the broader (re)casting of HIV prevention as a medical and technological problem that has been central to the recent 'end of AIDS' discourse. While HIV prevention discourses have been grounded in a neoliberal calculus of individual responsibility since the late 1990s, PrEP constitutes a pharmaceutical extension of the responsibilised sexual subject. Central to this extension are the acknowledgment of one's risk and a willingness to take pre-emptive medical action to secure a future without HIV. For men who have sex with men, a population heavily targeted for biomedical interventions in the United States, PrEP marks a shift in moral discourses of what it means to be a responsible sexual subject. Characteristics of the pharmaceutical extension of the neoliberal sexual subject are explored through an examination of a New York City-based PrEP promotional campaign.
HIV pre-exposure prophylaxis (PrEP) is a prevention technology that involves prescribing antiretroviral drugs to HIV-negative people to protect them from infection. This paper considers how the development of the technology has necessitated the parallel configuration of its users, and how this process has affected the perception and uptake of the technology. In designing a technology, potential users are typically defined, enabled and constrained, partly to create a target population (or market) for the technology, but also to reassure people that it can be used safely and effectively. This process may or may not be helpful for the uptake and use of the technology. Published research on PrEP indicates that while the technology was under trial, the primary focus was on the 'at-risk' subject in need of PrEP, with little or no consideration of the other qualities necessary for successful use. Post-trial accounts of PrEP have begun to outline desirable qualities of successful PrEP use, such as caution, compliance and being organised. It appears that the PrEP user was only partially configured during the technology's development, and the initial focus on risk has done little to counter fears of the technology, which may partially account for its slow uptake.
Mugwanya, Kenneth K; John-Stewart, Grace; Baeten, Jared
In settings where HIV is prevalent in heterosexual populations, pregnancy and postpartum breastfeeding periods can be associated with substantial HIV acquisition risk. Pre-exposure prophylaxis (PrEP) with daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine is an attractive HIV prevention option for women who are lactating but data are limited on its safety during the lactation period. Areas covered: We provide a concise synthesis and summary of current evidence on the safety of TDF-based PrEP during breastfeeding. We conducted a review, searching Pubmed database and major PrEP conferences for primary studies with TDF-based PrEP exposure during postpartum breastfeeding. Expert opinion: TDF-based oral PrEP is an effective female-controlled HIV prevention option. There is evidence supporting the safety of TDF use for infant outcomes during breastfeeding in antiretroviral treatment regimens for HIV and hepatitis B virus, and more limited, but consistently safe, data from use of TDF as PrEP. The potential for risk is arguably outweighed for at-risk individuals by HIV prevention benefits, including indirect protection to the infant as a result of preventing HIV in the breastfeeding mother. As PrEP delivery is scaled up in heterosexual populations in high HIV prevalence settings and for at-risk persons in other settings, implementation science studies can provide a framework to increase the accrual of safety, acceptability, and use data related to PrEP during lactation.
Moreno, Santiago; Antela, Antonio; García, Felipe; Del Amo, Julia; Boix, Vicente; Coll, Pep; Fortuny, Claudia; Sirvent, Juan L Gómez; Gutiérrez, Félix; Iribarren, José A; Llibre, Josep M; Quirós, Juan C López Bernaldo de; Losa, Juan Emilio; Lozano, Ana; Meulbroek, Michael; Olalla, Julián; Pujol, Ferran; Pulido, Federico; Crespo Casal, Manuel; García, Juan González; Aldeguer, José López; Molina, Jose A Pérez; Podzamczer Palter, Daniel; Román, Antonio Rivero
Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Strauss, Benjamin B; Greene, George J; Phillips, Gregory; Bhatia, Ramona; Madkins, Krystal; Parsons, Jeffrey T; Mustanski, Brian
Pre-exposure prophylaxis (PrEP) has shown promise as a safe and effective HIV prevention strategy, but there is limited research on awareness and use among young men who have sex with men (YMSM). Using baseline data from the "Keep It Up! 2.0" randomized control trial, we examined differences in PrEP awareness and use among racially diverse YMSM (N = 759; mean age = 24.2 years). Participants were recruited from study sites in Atlanta, Chicago, and New York City, as well as through national advertising on social media applications. While 67.5 % of participants reported awareness of PrEP, 8.7 % indicated using the medication. Awareness, but not use, varied by demographic variables. PrEP-users had twice as many condomless anal sex partners (ERR = 2.05) and more condomless anal sex acts (ERR = 1.60) than non-users. Future research should aim to improve PrEP awareness and uptake among YMSM and address condom use.
Yu, Wenya; Wang, Lu; Han, Na; Zhang, Xiayan; Mahapatra, Tanmay; Mahapatra, Sanchita; Babu, Giridhara R.; Tang, Weiming; Detels, Roger; Zhao, Jinkou
Antiretroviral drugs are being tried as candidates for the pre-exposure prophylaxis (PrEP) against HIV for a considerable period, due to their potential for immediate inhibition of viral replication. Discrepancies in the findings called for a critical review of the relevant efforts and their outcomes. A systematic literature search identified 143 eligible articles of which only 5 reported complete findings while another 11 were still on-going. Observed moderate efficacy and good safety profile seemed to identify PrEP as a promising step for minimizing the spread of HIV to relatively unaffected population and controlling the epidemic among high risk population groups. But the duration of this efficacy was found to depend heavily on the availability, adherence and other related issues like cost, political commitment, ethical consideration etc. To prevent potential cultural and behavioral modifications, proper pre-administration counseling also seemed critical for the success of PrEP as a cost-effective intervention with adequate coverage. PMID:25078629
Xu, J Y; Mou, Y C; Ma, Y L; Zhang, J Y
Objective: To evaluate the compliancy of HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in Chengdu, Sichuan province, and explore the influencing factors. Methods: From 1 July 2013 to 30 September 2015, a random, open, multi-center and parallel control intervention study was conducted in 328 MSM enrolled by non-probability sampling in Chengdu. The MSM were divided into 3 groups randomly, i.e. daily group, intermittent group (before and after exposure) and control group. Clinical follow-up and questionnaire survey were carried out every 3 months. Their PrEP compliances were evaluated respectively and multivariate logistic regression analysis was conducted to identify the related factors. Results: A total of 141 MSM were surveyed, in whom 59(41.8 % ) had good PrEP compliancy. The PrEP compliancy rate was 69.0 % in daily group, higher than that in intermittent group (14.3 % ), the difference had significance ( χ (2)=45.29, P <0.001). Multivariate logistic analysis indicated that type of PrEP was the influencing factors of PrEP compliancy. Compared with daily group, the intermittent group had worse PrEP compliancy ( OR =0.07, 95 %CI : 0.03-0.16). Conclusion: The PrEP compliance of the MSM in this study was poor, the compliancy would be influenced by the type of PrEP.
Lachowsky, Nathan J; Lin, Sally Y; Hull, Mark W; Cui, Zishan; Sereda, Paul; Jollimore, Jody; Rich, Ashleigh; Montaner, Julio S G; Roth, Eric A; Hogg, Robert S; Moore, David M
Men who have sex with men (MSM) account for approximately half of Canada's new HIV infections. Pre-exposure prophylaxis (PrEP), a recently established and effective HIV prevention tool for MSM is currently not approved nor publicly funded. We recruited MSM via respondent-driven sampling to complete a self-administered computer-based interview. Stratified by HIV status, multivariable logistic regression identified factors associated with PrEP awareness. Of 673 participants, 102/500 (20.9 %) HIV-negative and 63/173 (26.5 %) HIV-positive men were aware of PrEP, but none had used it. One third of PrEP-aware MSM spoke about it with friends or sex partners. Self-declared knowledge was limited. Factors associated with PrEP awareness varied by HIV status, but included greater HAART optimism for HIV-negative MSM. Among HIV-negative MSM, being PrEP unaware was associated with younger age, not always having condoms, and preferring receptive versus insertive anal sex. Future longitudinal research should identify early adopters of PrEP and its associated impacts.
Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M
Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.
Malone, Jowanna; Syvertsen, Jennifer L; Johnson, Blake E; Mimiaga, Matthew J; Mayer, Kenneth H; Bazzi, Angela R
Up to two-thirds of new cases of HIV transmission between gay, bisexual and other men who have sex with men in the USA are attributed to primary relationships. Understanding the relationship dynamics and sexual agreements of male-male couples can provide insight into HIV transmission patterns and prevention needs in this population. The daily use of antiretroviral pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, but its negotiation and use within social and intimate relationship contexts remain understudied. We conducted semi-structured qualitative interviews with 20 male couples (n = 40 men) in which at least one partner was either using or in the process of initiating PrEP. Congruent with a theoretical focus on social theories of relationships and negotiated risk, couples were interviewed about relationship dynamics, trust, communication and sexual health practices, including their perception and use of PrEP. Overall, we found that couples showed heightened trust and communication when establishing open, sexual agreements and demonstrated high awareness of sexual risks and health practices in the context of PrEP use. This study demonstrates how understanding relationship dynamics can better inform HIV prevention and sexual health promotion efforts for male couples at risk of HIV.
Should travellers to rabies-endemic countries be pre-exposure vaccinated? An assessment of post-exposure prophylaxis and pre-exposure prophylaxis given to Danes travelling to rabies-endemic countries 2000-12.
Christiansen, Annette H; Rodriguez, Anna B; Nielsen, Jens; Cowan, Susan A
Since 2000, a steady increase of vaccines used for both rabies Post-exposure prophylaxis (PEP) and rabies Pre-exposure prophylaxis (PrEP) given to Danish travellers was observed. This study aims to evaluate whether the increase of PEP and PrEP was due to increased travelling, increased awareness of the need for PrEP, or more animal bites per travel, leading to more PEP being administered, in order to assess the need for changing the recommendations. We also described in which countries Danish travelers most frequently reported possible exposure to rabies, and evaluated the timeliness of rabies PEP, including rabies immunoglobulin (RIG). We included all Danes reported to the National Database for Rabies Treatment as having started rabies PEP either abroad or after returning to Denmark, between 2000 and 2012. Data on the yearly number of Danish travelers from 2004 to 2012 to Thailand were collected to calculate the incidence of animal bites at this destination. We also included data on rabies vaccines sold for PrEP or for booster vaccination in Denmark. PEP after possible exposure to rabies abroad increased yearly by 8.8 %. Likewise vaccines sold for PrEP increased by 8.2% annually. The number of Danish travelers to Thailand increased by 7.3% per year, resulting in a stable incidence of animal bites per 100,000 travelers. Seventy-five % started PEP in the country of exposure, while only 10 % received RIG. The yearly increase in PEP and PrEP are parallel to the yearly increase in number of travelers, and can thus be explained by the increased rate of traveling, and not by a rise in awareness of rabies risk or more bites per traveler.Even short term travelers should be given the option of including PrEP in their travel immunisation program, as PEP and especially RIG is not always available in rabies-endemic countries. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: firstname.lastname@example.org.
Seth C Kalichman; Lisa Eaton
Abstract Introduction: Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. Methods: HIV-negative sexually active men who have sex with men (N?=?2...
Adam Bourne; Matteo Cassolato; Clayton Koh Thuan Wei; Bangyuan Wang; Joselyn Pang; Sin How Lim; Iskandar Azwa; Ilias Yee; Gitau Mburu
Abstract Background: Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers t...
Mugo, Peter Mwangi; Sanders, Eduard J.; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R.; Priddy, Frances H.; Haberer, Jessica E.
A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:...
Dolling, David I; Desai, Monica; McOwan, Alan; Gilson, Richard; Clarke, Amanda; Fisher, Martin; Schembri, Gabriel; Sullivan, Ann K; Mackie, Nicola; Reeves, Iain; Portman, Mags; Saunders, John; Fox, Julie; Bayley, Jake; Brady, Michael; Bowman, Christine; Lacey, Charles J; Taylor, Stephen; White, David; Antonucci, Simone; Gafos, Mitzy; McCormack, Sheena; Gill, Owen N; Dunn, David T; Nardone, Anthony
Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in
Ariane van der Straten
Full Text Available In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF, we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE.In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41, serial ethnographic interviews (n = 21, or focus group discussions (n = 40. Audiotaped interviews were transcribed, translated, and coded thematically for analysis.Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use.Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial
Khan, Arshad Bashir; Thakur, Ram Sharnagat
To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF). It may provide pre-exposure prophylaxis for women against HIV. TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr's index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies. Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague-Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40 ± 2 °C and 75 ± 5% RH for six months. C1 was selected as the best formulation due to better swelling index (65.93% at 24 h), prolonged release of 100.62% cumulative drug release (CDR) at 24 h, superior mucoadhesion force (35.93 × 10 2 dynes/cm 2 ) and retention time (16 h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.
Kim, Sun Bean; Yoon, Myoungho; Ku, Nam Su; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Kim, Changsoo; Kwon, Hee-Dae; Lee, Jeehyun; Smith, Davey M; Choi, Jun Yong
Multiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation. We constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures. Overall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together. This model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.
Okoro, Olihe; Hillman, Lisa
The study objectives were to a) assess knowledge and experience; b) describe perceptions and attitudes; and c) identify training needs of community-based pharmacists regarding HIV pre-exposure prophylaxis (PrEP). This was a cross-sectional survey study. The survey was administered online to pharmacists practicing in a community setting in the state of Minnesota. Measures included knowledge of and experience with HIV PrEP, perceptions and attitudes towards pharmacists' involvement, and HIV PrEP-specific training needs for pharmacists. With a survey response rate of approximately 13% (n = 347), most respondents (76.4%) agreed that HIV PrEP can be beneficial in high-risk populations. Forty-six percent of respondents were not aware of U.S. Food and Drug Administration approval of emtricitabine and tenofovir disoproxil fumarate for PrEP. Most respondents (71.1%) were "not at all familiar" with Centers for Disease Control and Prevention guidelines for PrEP. Twenty-one percent of respondents had sufficient knowledge to counsel patients on PrEP. Experience with counseling on PrEP (21.8%), having dispensed PrEP in the last 2 years (33.1%), fewer years in practice (≤10 years), location of practice site (urban or suburban), and having received HIV continuing education in the last 2 years (33.0%) were associated with more knowledge of HIV PrEP. Top concerns with counseling were knowledge about the medication and behavior modification. The most frequently indicated primary concerns with implementing PrEP initiatives were identifying appropriate candidates and patient adherence. As pharmacists' roles continue to expand, relevant content in pharmacy education and requisite training (including continuing education) are critical to addressing knowledge gaps and competencies that will enable pharmacists engage more effectively in public health efforts such as HIV prevention. Published by Elsevier Inc.
van der Straten, Ariane; Stadler, Jonathan; Montgomery, Elizabeth; Hartmann, Miriam; Magazi, Busiswe; Mathebula, Florence; Schwartz, Katie; Laborde, Nicole; Soto-Torres, Lydia
In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE. In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis. Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use. Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and
Wood, Brian R; McMahan, Vanessa M; Naismith, Kelly; Stockton, Jonathan B; Delaney, Lori A; Stekler, Joanne D
We aimed to assess HIV pre-exposure prophylaxis (PrEP) awareness and prescribing practices among Washington State medical providers from diverse professional disciplines and practice types. In May 2016, we administered an anonymous online survey to licensed medical practitioners who provide primary, longitudinal, walk-in, emergency, obstetric, gynecologic, sexually transmitted infection (STI), or family planning care. Of 735 eligible providers, 64.8% had heard of PrEP. Younger providers and providers with a Doctor of Medicine (MD) degree were more likely to be aware of PrEP compared to older providers (p=0.0001) and providers of other training backgrounds (Advanced Registered Nurse Practitioner [ARNP], Doctor of Osteopathic Medicine [DO], or Physician Assistant [PA]) (p=0.04). Among providers aware of PrEP, most frequent reported concerns about prescribing were adherence (46.0%) and costs (42.9%). Providers felt very (20.1%) or somewhat (33.8%) comfortable discussing PrEP overall, but very (26.8%) or somewhat (44.7%) uncomfortable discussing cost and insurance issues. The 124 PrEP prescribers reported a median of 2 (range 1-175, total 1,142) patients prescribed PrEP. Prior authorizations and insurance denials had prevented prescriptions for 28.7% and 12.1% of prescribers, respectively. Interventions to improve PrEP access should include education to inform medical providers about PrEP, with particular attention to provider types less likely to be aware. Continued efforts to eliminate cost and insurance barriers and educate providers regarding financial resources would help improve PrEP access.
Thavorn, Kednapa; Kugathasan, Howsikan; Tan, Darrell H S; Moqueet, Nasheed; Baral, Stefan D; Skidmore, Becky; MacFadden, Derek; Simkin, Anna; Mishra, Sharmistha
Pre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes. We will systematically search electronic databases (MEDLINE, Embase) and the gray literature. We will include economic evaluation studies that assess both costs and health outcomes of PrEP in HIV-uninfected individuals, without restricting language or year of publication. Two reviewers will independently screen studies using predefined inclusion criteria, extract data, and assess methodological quality using the Philips checklist, Second Panel on the Cost-effectiveness of Health and Medicines, and the International Society for Pharmacoeconomics and Outcomes Research recommendations. Outcomes of interest include incremental costs and outcomes in natural units or utilities, cost-effectiveness ratios, and net monetary benefit. We will perform descriptive and quantitative syntheses using sensitivity analyses of outcomes by population subgroups, HIV epidemic settings, study designs, baseline intervention contexts, key parameter inputs and assumptions, type of outcomes, economic perspectives, and willingness to pay values. Findings will guide future economic evaluation of PrEP strategies in terms of
The impending implementation of pre-exposure prophylaxis (PrEP) has prompted complicated bioethical and public health ethics concerns regarding the moral distribution of antiretroviral medications (ARVs) to ostensibly healthy populations as a form of HIV prevention when millions of HIV-positive people still lack access to ARVs globally. This manuscript argues that these questions are, in part, concerns over the ethics of the knowledge production practices of epidemiology. Questions of distribution, and their attendant cost-benefit calculations, will rely on a number of presupposed, and therefore, normatively cultural assumptions within the science of epidemiology specifically regarding the ability of epidemiologic surveillance to produce accurate maps of HIV throughout national populations. Specifically, ethical questions around PrEP will focus on who should receive ARVs given the fact that global demand will far exceed supply. Given that sexual transmission is one of the main modes of HIV transmission, these questions of 'who' are inextricably linked to knowledge about sexual personhood. As a result, the ethics of epidemiology, and how the epidemiology of HIV in particular conceives, classifies and constructs sexual populations will become a critical point of reflection and contestation for bioethicists, health activists, physicians, nurses, and researchers in the multi-disciplinary field of global health. This paper examines how cultural conundrums within the fields of bioethics and public health ethics are directly implicated within the ethics of PrEP, by analyzing the problems of population inaugurated by the construction of the men who have sex with men (MSM) epidemiologic category in the specific national context of South Africa. © 2013 John Wiley & Sons Ltd.
Lusti-Narasimhan, Manjula; Khosla, Rajat; Baggaley, Rachel; Temmerman, Marleen; McGrory, Elizabeth; Farley, Tim
Two new microbicide products based on topical (vaginal) application of antiretroviral drugs - 1% tenofovir gel and the dapivirine ring - are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Given that these new topical PrEP products are designed to be woman initiated and will likely be delivered in reproductive health settings, it is important to ensure that the guidance be framed in the context of comprehensive sexual and reproductive health and human rights. In addition to the safety and effectiveness data resulting from clinical trials, and the regulatory approval required for new products, the WHO normative guidelines on the use of topical PrEP will be essential for rapid roll-out in countries. Human rights standards and principles provide a framework for the provision of woman-initiated HIV prevention products. These include addressing issues related to the gender inequities which are linked to the provision of HIV-prevention, treatment and care for young girls and women. Effective programming for women and girls must therefore be based on understanding the local, social and community contexts of the AIDS epidemic in the country, and adapting HIV strategies and programmes accordingly. Such a framework therefore is needed not only to ensure optimal uptake of these new products by women and girls but also to address sociocultural barriers to women's and girls' access to these products.
Colby, Donn; Srithanaviboonchai, Kriengkrai; Vanichseni, Suphak; Ongwandee, Sumet; Phanuphak, Nittaya; Martin, Michael; Choopanya, Kachit; Chariyalertsak, Suwat; van Griensven, Frits
Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country. Thailand was one of the first countries in the world to successfully reverse a generalized HIV epidemic. Despite this early success, HIV prevalence has remained high among people who inject drugs and has surged among men who have sex with men (MSM) and transgender women (TGW). Two pivotal trials that showed that the use of oral antiretroviral medication as PrEP can reduce HIV transmission were conducted partially or entirely at Thai sites. Demonstration projects of PrEP, as well as clinical trials of alternative PrEP regimens, began or will begin in 2014-2015 in Thailand and will provide additional data and experience on how to best implement PrEP for high-risk individuals in the community. Financing of drug costs, the need for routine laboratory monitoring and lack of awareness about PrEP among at-risk groups all present challenges to the wider implementation of PrEP for HIV prevention in Thailand. Although significant challenges to wider use remain, PrEP holds promise as a safe and highly effective method to be used as part of a combined HIV prevention strategy for MSM and TGW in Thailand.
Bazzi, Angela R; Leech, Ashley A; Biancarelli, Dea L; Sullivan, Meg; Drainoni, Mari-Lynn
Antiretroviral pre-exposure prophylaxis (PrEP) is a promising HIV prevention strategy for HIV serodiscordant couples (HIV-infected male, uninfected female) seeking safer conception. However, most research on PrEP for safer conception has focused on couples in sub-Saharan Africa; little is known about the perspectives or experiences of heterosexual couples in the United States. We conducted qualitative interviews with six couples (six women and five of their male partners) receiving PrEP for conception services at an urban safety net hospital in the US Northeast. In-depth interview guides explored couple relationships and contextual factors and attitudes, perceptions, and decision-making processes surrounding PrEP for safer conception. Thematic analyses focused on identifying the following emergent themes. We found that couple relationships were situated within broader social and cultural contexts of immigration, family, and community that shaped their experiences with HIV and serodiscordant relationship status. Despite strong partner support within relationships, HIV stigma and disapproval of serodiscordant relationships contributed to couples' feelings of social isolation and subsequent aspirations to have "normal" families. By enabling "natural" conception through condomless sex, PrEP for safer conception provided a sense of enhanced relationship intimacy. Couples called for increasing public awareness of PrEP through positive messaging as a way to combat HIV stigma. Findings suggest that relationship dynamics and broader social contexts appear to shape HIV serodiscordant couples' fertility desires and motivations to use PrEP. However, increased public awareness of PrEP for safer conception may be needed to combat HIV stigma at the community level.
Hampel, B; Kusejko, K; Braun, D L; Harrison-Quintana, J; Kouyos, R; Fehr, J
HIV pre-exposure prophylaxis (PrEP) is not approved in Switzerland and therefore must be paid for by the users themselves. We conducted a survey to find out whether men who have sex with men (MSM) in Switzerland are already taking PrEP, or are considering using it, and whether it is being taken under medical supervision or not. Grindr® is a geosocial networking app for MSM. Between 5 and 24 January 2017, users of the app who were located in Switzerland by a global positioning system (GPS) were asked to participate in a ten-question survey on PrEP use. Of the 2455 people who took part in the survey, 1893 were included in the analysis. Eighty-two participants (4.3%) reported that they were currently taking PrEP, 64 of whom (78%) said that they were under medical supervision. Seven PrEP users (9%) declared that they had not taken an HIV test within the previous 12 months. Nine hundred and forty-four (49.9%) were considering taking PrEP in the next 6 months, and 1474 (77.9%) were considering taking it at some point in the future. In an online survey carried out among sexually active MSM in Switzerland, only a minority of the individuals approached responded that they were currently using PrEP. However, the majority of participants were considering taking PrEP in the future. We identified a substantial proportion of PrEP users taking PrEP outside a medical setting. Hence, a national programme facilitating access to medical care and providing PrEP is urgently needed. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.
Kessler, Jason; Myers, Julie E.; Nucifora, Kimberly A.; Mensah, Nana; Toohey, Christopher; Khademi, Amin; Cutler, Blayne; Braithwaite, R. Scott
Objective To compare the value and effectiveness of different prioritization strategies of pre-exposure prophylaxis (PrEP) in New York City (NYC). Design Mathematical modeling utilized as clinical trial is not feasible. Methods Using a model accounting for both sexual and parenteral transmission of HIV we compare different prioritization strategies (PPS) for PrEP to two scenarios—no PrEP and PrEP for all susceptible at-risk individuals. The PPS included PrEP for all MSM, only high-risk MSM, high-risk heterosexuals, and injection drug users, and all combinations of these four strategies. Outcomes included HIV infections averted, and incremental cost effectiveness (per-infection averted) ratios. Initial assumptions regarding PrEP included a 44% reduction in HIV transmission, 50% uptake in the prioritized population and an annual cost per person of $9,762. Sensitivity analyses on key parameters were conducted. Results Prioritization to all MSM results in a 19% reduction in new HIV infections. Compared to PrEP for all persons at-risk this PPS retains 79% of the preventative effect at 15% of the total cost. PrEP prioritized to only high-risk MSM results in a reduction in new HIV infections of 15%. This PPS retains 60% of the preventative effect at 6% of the total cost. There are diminishing returns when PrEP utilization is expanded beyond this group. Conclusions PrEP implementation is relatively cost-inefficient under our initial assumptions. Our results suggest that PrEP should first be promoted among MSM who are at particularly high-risk of HIV acquisition. Further expansion beyond this group may be cost-effective, but is unlikely to be cost-saving. PMID:25493594
Murnane, Pamela M; Heffron, Renee; Ronald, Allan; Bukusi, Elizabeth A; Donnell, Deborah; Mugo, Nelly R; Were, Edwin; Mujugira, Andrew; Kiarie, James; Celum, Connie; Baeten, Jared M
For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities. In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing. For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms). PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.
Krakower, Douglas; Mayer, Kenneth H.
As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic. PMID:22821365
Velloza, Jennifer; Heffron, Renee
This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.
Lennart P. Maljaars
Full Text Available Background: Approximately 3 million adolescents and young adults (AYA, between the ages of 15 years and 24 years, are living with HIV in sub-Saharan Africa. The use of pre-exposure prophylaxis (PrEP may be a promising HIV prevention tool to bridge the high-risk years of AYA between sexual debut and adulthood. Objectives: Concerns have been raised that the use of PrEP could lead to an increase in sexual risk behaviour and sexually transmitted infections in general and less condom use in particular among adolescents. Methods: This study assesses condom use among South African adolescents enrolled on a demonstration PrEP study, called Pluspills, being conducted in Cape Town and Soweto. A questionnaire on sexual risk behaviour was administered at baseline and after 4, 8 and 12 weeks. Three different questions on condom use were asked at each visit. Unless all answers indicated condom use at all times, a participant was scored ‘at risk’. McNemar’s tests and a Cochran’s Q test were used to investigate changes in condom use over time. Results: We interviewed 148 adolescents (66% female at baseline. Eighty-nine participants completed all visits. In this group, an increase in condom use was observed over the period of 12 weeks. Most participants who reported behavioural changes mentioned an increase in condom use. Conclusion: There was no sign of sexual risk compensation in the 12 weeks of the study. Observed increase in condom use can be explained by an increased awareness of personal HIV risk or by social desirability or recall biases. In future research, additional data including other biomarkers of unprotected sex and longer follow-up time would be useful to help understand the relationship between PrEP use, sexual risk perception and consequent behaviours, especially in adolescents.
Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter
Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV.
Rolle, Charlotte-Paige; Rosenberg, Eli S; Luisi, Nicole; Grey, Jeremy; Sanchez, Travis; Del Rio, Carlos; Peterson, John L; Frew, Paula M; Sullivan, Patrick S; Kelley, Colleen F
PrEP willingness may be different among black and white men who have sex with men (MSM) given known disparities in HIV incidence, sociodemographic factors, and healthcare access between these groups. We surveyed 482 black and white HIV-negative MSM in Atlanta, GA about their willingness to use pre-exposure prophylaxis (PrEP) and facilitators and barriers to PrEP willingness. Overall, 45% (215/482) of men indicated interest in using PrEP. Engaging in recent unprotected anal intercourse (UAI) was the only factor significantly associated with PrEP willingness in multivariate analyses (OR 1.73, 95% CI 1.13, 2.65). Willing men identified "extra protection" against HIV as the most common reason for interest in using PrEP, whereas unwilling men most commonly cited not wanting to take medication daily, and this reason was more common among white MSM (42.3% of white MSM vs. 28.9% of black MSM, p = 0.04). Most men indicated willingness to use PrEP if cost was <50 dollars/month; however, more black MSM indicated willingness to use PrEP only if cost were free (17.9% of white MSM vs. 25.9% of black MSM, p = 0.03). Overall, these data are useful to scale up PrEP interventions targeting at-risk MSM in Atlanta and highlight the need for implementation of low cost-programs, which will be especially important for black MSM.
Zimet, Gregory; Lally, Michelle; Kahn, Jessica A.
Abstract Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is currently indicated for use in adults in the United States and may soon be indicated for minor adolescents. However, implementation of PrEP use among minors may present unique barriers. We conducted 15 individual, semi-structured interviews among US clinicians caring for HIV-infected and at-risk youth. The theory-driven interview guide assessed demographics, perceived role of oral PrEP in HIV prevention among adolescents, perceived barriers to and facilitating factors for use of PrEP in adolescents, and clinician-reported likelihood of prescribing PrEP. Transcripts were analyzed using framework analysis. Overall, clinicians viewed PrEP as a time-limited intervention that is one part of a comprehensive approach to HIV prevention among adolescents. Perceived barriers to prescribing to minors included concerns about: confidentiality, legality of minors consenting to PrEP without parental involvement, ability of minors to understand the risks/benefits of PrEP, the possible impact of PrEP on bone accrual, off-label use of PrEP medication in minors, and the high costs associated with PrEP use. Clinician-reported facilitating factors for prescribing PrEP to youth included educating communities and other clinicians about PrEP, ensuring adequate financial resources and infrastructure for delivering PrEP, developing formal guidance on effective behavioral interventions that should be delivered with PrEP, and gaining personal experience with prescribing PrEP. Clinicians indicated greater comfort with prescribing PrEP to adults versus minors. For PrEP to become more widely available to youth at risk for HIV infection, barriers that are unique to PrEP use in minors must be addressed. PMID:27410497
Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris
In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive "combination prevention" programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers' openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.
Ong, Koh Jun; Desai, Sarika; Field, Nigel; Desai, Monica; Nardone, Anthony; van Hoek, Albert Jan; Gill, Owen Noel
Clinical effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV acquisition in men who have sex with men (MSM) at high HIV risk is established. A static decision analytical model was constructed to inform policy prioritisation in England around cost-effectiveness and budgetary impact of a PrEP programme covering 5,000 MSM during an initial high-risk period. National genitourinary medicine clinic surveillance data informed key HIV risk assumptions. Pragmatic large-scale implementation scenarios were explored. At 86% effectiveness, PrEP given to 5,000 MSM at 3.3 per 100 person-years annual HIV incidence, assuming risk compensation (20% HIV incidence increase), averted 118 HIV infections over remaining lifetimes and was cost saving. Lower effectiveness (64%) gave an incremental cost-effectiveness ratio of + GBP 23,500 (EUR 32,000) per quality-adjusted life year (QALY) gained. Investment of GBP 26.9 million (EUR 36.6 million) in year-1 breaks even anywhere from year-23 (86% effectiveness) to year-33 (64% effectiveness). PrEP cost-effectiveness was highly sensitive to year-1 HIV incidence, PrEP adherence/effectiveness, and antiretroviral drug costs. There is much uncertainty around HIV incidence in those given PrEP and adherence/effectiveness, especially under programme scale-up. Substantially reduced PrEP drug costs are needed to give the necessary assurance of cost-effectiveness, and for an affordable public health programme of sufficient size.
Wheeler, Stephanie B.; Stranix-Chibanda, Lynda; Hosek, Sybil G.; Watts, D. Heather; Siberry, George K.; Spiegel, Hans M. L.; Stringer, Jeffrey S.; Chi, Benjamin H.
Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. Methods: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. Results: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. Conclusions: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy. PMID:27355502
Grace, Daniel; Jollimore, Jody; MacPherson, Paul; Strang, Matthew J P; Tan, Darrell H S
With the emergence of daily oral tenofovir disoproxil fumarate and emtricitabine-based pre-exposure prophylaxis (PrEP) use in Canada, questions have emerged concerning the impacts of this HIV prevention tool on gay men's social and sexual lives. We conducted small focus groups and individual qualitative interviews with 16 gay men in Toronto who were part of the 'first wave' of Canadian PrEP users. Participants were on PrEP for at least one year as part of a demonstration project (November 2014-June 2016). These participants accessed PrEP before regulatory approval by Health Canada in February 2016. The mean age of participants was 37.6 years (SD 11.02); 94% completed secondary education, and 69% were white. Sex-stigma emerged as a complex theme in men's accounts of PrEP use across three overlapping domains: (1) PrEP-related stigma, including discussions of concealment and stigma from friends, family, and sexual partners, (2) PrEP as a perceived tool for combating HIV-related stigma, where some men said that they no longer discussed HIV status with sexual partners, and (3) PrEP as illuminating structural stigma, where it was attributed to unmasking stigma related to sex and sexuality. For some participants, PrEP has allowed for liberating sex and a self-described return to normalcy-normal, exciting, pleasurable sex that was no longer reliant on condom use. Paradoxically, some men said that PrEP use both led them to experience stigmatizing reactions within their social and sexual networks, while also helping to remove stigma, shame, and fear related to HIV, sexuality, and sex with gay men living with HIV.
Full Text Available 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.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.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.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.
Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G
Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.
Blackstock, Oni J; Moore, Brent A; Berkenblit, Gail V; Calabrese, Sarah K; Cunningham, Chinazo O; Fiellin, David A; Patel, Viraj V; Phillips, Karran A; Tetrault, Jeanette M; Shah, Minesh; Edelman, E Jennifer
Among health care providers, prescription of HIV pre-exposure prophylaxis (PrEP) has been low. Little is known specifically about primary care physicians (PCPs) with regard to PrEP awareness and adoption (i.e., prescription or referral), and factors associated with adoption. To assess PrEP awareness, PrEP adoption, and factors associated with adoption among PCPs. Cross-sectional online survey conducted in April and May 2015. Members of a national professional organization for academic primary care physicians (n = 266). PrEP awareness, PrEP adoption (ever prescribed or referred a patient for PrEP [yes/no]), provider and practice characteristics, and self-rated knowledge, attitudes, and beliefs associated with adoption. The survey response rate was 8.6 % (266/2093). Ninety-three percent of respondents reported prior awareness of PrEP. Of these, 34.9 % reported PrEP adoption. In multivariable analysis of provider and practice characteristics, compared with non-adopters, adopters were more likely to provide care to more than 50 HIV-positive patients (vs. 0, aOR = 6.82, 95 % CI 2.06-22.52). Compared with non-adopters, adopters were also more likely to report excellent, very good, or good self-rated PrEP knowledge (15.1 %, 33.7 %, 30.2 % vs. 2.5 %, 18.1 %, 23.8 %, respectively; p < 0.001) and to perceive PrEP as extremely safe (35.1 % vs. 10.7 %; p = 0.002). Compared with non-adopters, adopters were less likely to perceive PrEP as being moderately likely to increase risk behaviors ("risk compensation") (12.8 % vs. 28.8 %, p = 0.02). While most respondents were aware of PrEP, only one-third of PrEP-aware PCPs reported adoption. Adopters were more likely to have experience providing HIV care and to perceive PrEP as extremely safe, and were less likely to perceive PrEP use as leading to risk compensation. To enhance PCP adoption of PrEP, educational efforts targeting PCPs without HIV care experience should be considered, as well as training
Witzel, TC; Nutland, W; Bourne, A
Black men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared to other MSM, despite similar levels of condom use and testing. Pre-exposure prophylaxis (PrEP) could be a useful intervention to reduce these inequalities. This research therefore aims to understand the dimensions of acceptability of a potential PrEP service for BMSM aged 18-45 years in London. In-depth semi-structured interviews were conducted with 25 PrEP-eligible BMSM between April and August 201...
Karuga, Robinson Njoroge; Njenga, Serah Nduta; Mulwa, Rueben; Kilonzo, Nduku; Bahati, Prince; O?reilley, Kevin; Gelmon, Lawrence; Mbaabu, Stephen; Wachihi, Charles; Githuka, George; Kiragu, Michael
Background The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. Th...
Jaspal, Rusi; Daramilas, C.
open access article Pre-exposure prophylaxis (PrEP) is a novel bio-medical HIV prevention op- tion for individuals at high risk of HIV exposure. This qualitative interview study ex- plores perceptions and understandings of PrEP among a sample of 20 HIV-negative and HIV-positive men who have sex with men (MSM) in the UK, where there is a debate about the feasibility of o ering PrEP on the NHS. Data were analysed using qualitative thematic analysis and social representations theory from soci...
Franks, Julie; Hirsch-Moverman, Yael; Loquere, Avelino S; Amico, K Rivet; Grant, Robert M; Dye, Bonnie J; Rivera, Yan; Gamboa, Robert; Mannheimer, Sharon B
The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use.
Doblecki-Lewis, Susanne; Lester, Larissa; Schwartz, Bryanna; Collins, Constance; Johnson, Rai; Kobetz, Erin
Pre- and non-occupational post-exposure prophylaxis for the prevention of HIV infection are recommended for adults at substantial risk of HIV. Women experiencing homelessness have increased risk of HIV infection compared with stably-housed women. We conducted a survey of 74 sheltered women at Lotus House Women's Shelter (Lotus House) in Miami to assess risk behaviour as well as knowledge and perception of pre- and non-occupational post-exposure prophylaxis in this population. Of surveyed women, 58.1% engaged in vaginal and/or anal sex while sheltered, and of sexually-active women 55.4% reported inconsistent condom use. 83.8% of women reported no concern regarding HIV acquisition due to their behaviour. Few women surveyed (20.8%) had previously heard of pre- or non-occupational post-exposure prophylaxis. The majority (58.3%) of respondents indicated receptiveness to these prevention methods when introduced. Those indicating that they would consider pre- or non-occupational post-exposure prophylaxis were significantly younger than those indicating that they would not consider these prevention strategies (p = 0.004). Education and referral for pre- and non-occupational post-exposure prophylaxis should be considered for sheltered women at risk of HIV infection. Additional research to optimise implementation of biomedical prevention strategies in this population is needed. © The Author(s) 2015.
Bond, Keosha T; Gunn, Alana J
Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug.
Scott, Hyman M; Klausner, Jeffrey D
Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in "real world" reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.
Marra, Elske; Hankins, Catherine A.
Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the
Balzer, Laura; Staples, Patrick; Onnela, Jukka-Pekka; DeGruttola, Victor
Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger
Caceres, Carlos F.; Segura, Eddy R.; Grant, Robert M.; Garnett, Geoff P.; Hallett, Timothy B.
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
Gabriela B Gomez
Full Text Available 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.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
Full Text Available Nearly ten randomized controlled trials (RCTs of pre-exposure prophylaxis (PrEP have been completed or are ongoing worldwide to evaluate the effectiveness of PrEP in HIV transmission among HIV-uninfected high risk populations. The purpose of this study was to evaluate the role of PrEP to prevent HIV transmission through a Mata-analysis.A comprehensive computerized literature search was carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wan Fang, CNKI and related websites to collect relevant articles (from their establishment date to August 30, 2013. The search terms were "pre-exposure prophylaxis", "high risk population", "HIV infection", "reduction", "relative risk" and "efficacy". We included any RCT assessing PrEP for the prevention of HIV infection in high risk populations. Interventions of the studies were continuously daily or intermittent doses of single or compound antiretrovirals (ARVs before HIV exposure or during HIV exposure. A meta-analysis was conducted using Stata 10.0. A random-effects method was used to calculate the pooled relative risk (RR and 95% confidence intervals (CI for all studies included.Seven RCTs involving 14,804 individuals in high risk populations were eligible for this study. The number of subjects in the experimental groups was 8,195, with HIV infection rate of 2.03%. The number of subjects in the control groups was 6,609, with HIV infection rate of 4.07%. The pooled RR was 0.53 (95% CI = 0.40 ∼ 0.71, P<0.001. The re-analyzed pooled RR were 0.61 (95% CI = 0.48 ∼ 0.77, P<0.001, 0.49 (95% CI = 0.38 ∼ 0.63, P<0.001, respectively, by excluding the largest study or two studies without statistical significance. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 1,022.These results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.
Deray, Raffy; Rivera, Cesar; Gripon, Shiela; Ulanday, Corazon; Roces, Maria Concepcion; Amparo, Anna Charinna; Attlan, Michael; Demont, Clarisse; Kieffer, Alexia; Miranda, Mary Elizabeth
Rabies remains endemic in the Philippines. A study was conducted in El Nido, Palawan, Philippines to: (i) detect the true incidence of animal bites in school children aged 5-14 years using active surveillance and compare these data to estimates from the existing passive surveillance system, (ii) evaluate the impact of rabies prevention education and pre-exposure prophylaxis (PrEP) on animal bite incidence, and (iii) assess the health economic impact of the interventions. A cohort of 4,700 school children was followed-up for any suspect rabies exposures between January 2011 and December 2012. Data on animal bite incidence from the study cohort were compared to that obtained from a review of consultation records at the Animal Bite Treatment Center (ABTC). PrEP was offered to children in all 27 public elementary schools in El Nido (in January to February 2012). Teachers were given a manual for integrating rabies in the public elementary school curriculum during the school year 2012-13. Active surveillance of the cohort revealed a higher incidence of suspect rabies exposures than that from passive surveillance. Despite a decrease in the number of Category III bites, there was no significant decrease in overall bite incidence as a result of the interventions. However, there was an increase in rabies awareness among school children in all grade levels. There was also a high level of acceptability of PrEP. Children who received PrEP and subsequently were bitten only needed two booster doses for post-exposure prophylaxis, resulting in substantial cost-savings. The true burden of animal bites remains underestimated in ABTC records. PrEP is advantageous in selected population groups, i.e. school-aged children in rabies endemic areas with limited access to animal and human rabies prevention services. Educating school children is beneficial. Strengthening veterinary interventions to target the disease at source is important.
Mullins, Tanya L Kowalczyk; Zimet, Gregory; Lally, Michelle; Xu, Jiahong; Thornton, Sarah; Kahn, Jessica A
Pre-exposure prophylaxis (PrEP) is indicated for use in US adults, and little is known about clinician intentions to prescribe and actual prescription of PrEP to adolescents younger than 18. Fifty-six clinicians who care for HIV-infected and at-risk youth completed an anonymous online survey in 2014. Primary outcomes were (1) intentions to prescribe PrEP to adolescents and adults in four risk categories [men who have sex with men (MSM), transgender women, heterosexuals with multiple partners of unknown HIV status, heterosexuals with HIV-infected partners]; and (2) actual prescription of PrEP to adolescents and adults in these risk groups. Independent variables included clinician characteristics, experience prescribing nonoccupational postexposure prophylaxis, familiarity with and knowledge of PrEP and PrEP guidance, attitudes toward PrEP, and facilitating factors for prescribing PrEP and incorporation of PrEP guidance into practice. Variables associated with intention to prescribe ("very likely to prescribe" vs. other responses) and actual prescription of PrEP stratified by age and risk category were identified in logistic regression models. Mean age was 45.9 years (standard deviation 10.7); 64% were physicians. More clinicians reported high intention to prescribe PrEP to adult versus adolescent MSM (p = 0.02) and transgender women (p = 0.001). Variables associated with intention to prescribe and prescription of PrEP differed by age and risk category. In adolescents, those variables included positive beliefs, higher number of facilitating factors, and fewer barriers to PrEP prescription. Designing strategies based on these findings that address both facilitating factors and barriers to PrEP prescription may improve PrEP uptake by at-risk youth.
Peitzmeier, Sarah M; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Sherman, Susan G; Glass, Nancy; Beyrer, Chris; Decker, Michele R
Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.
Calabrese, Sarah K; Underhill, Kristen; Earnshaw, Valerie A; Hansen, Nathan B; Kershaw, Trace S; Magnus, Manya; Krakower, Douglas S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F
Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting ("beneficiary") and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts.
Brooks, Ronald A.; Kaplan, Rachel L.; Lieber, Eli; Landovitz, Raphael J.; Lee, Sung-Jae; Leibowitz, Arleen A.
The purpose of this study was to identify factors that may facilitate or impede future adoption of pre-exposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men in HIV-serodiscordant relationships. This qualitative study utilized semi-structured interviews conducted with a multi-racial/ethnic sample of 25 gay and bisexual HIV serodiscordant male couples (n=50 individuals) recruited from community settings in Los Angeles, California. A modified grounded theory approach was employed to identify major themes relating to future adoption of PrEP for HIV prevention. Motivators for adoption included protection against HIV infection, less concern and fear regarding HIV transmission, the opportunity to engage in unprotected sex, and endorsements of PrEP’s effectiveness. Concerns and barriers to adoption included the cost of PrEP, short- and long-term side effects, adverse effects of intermittent use or discontinuing PrEP, and accessibility of PrEP. The findings suggest the need for a carefully planned implementation program along with educational and counseling interventions in the dissemination of an effective PrEP agent. PMID:21476147
Ariën, Kevin K; Venkatraj, Muthusamy; Michiels, Johan; Joossens, Jurgen; Vereecken, Katleen; Van der Veken, Pieter; Abdellati, Saïd; Cuylaerts, Vicky; Crucitti, Tania; Heyndrickx, Leo; Heeres, Jan; Augustyns, Koen; Lewi, Paul J; Vanham, Guido
Pre-exposure prophylaxis and topical microbicides are important strategies in the prevention of sexual HIV transmission, especially since partial protection has been shown in proof-of-concept studies. In search of new candidate drugs with an improved toxicity profile and with activity against common non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV, we have synthesized and investigated a library of 60 new diaryltriazine analogues. From this library, 15 compounds were evaluated in depth using a broad armamentarium of in vitro assays that are part of a preclinical testing algorithm for microbicide development. Antiviral activity was assessed in a cell line, and in primary human cells, against both subtype B and subtype C HIV-1 and against viruses resistant to therapeutic NNRTIs and the candidate NNRTI microbicide dapivirine. Toxicity towards primary blood-derived cells, cell lines originating from the female reproductive tract and female genital microflora was also studied. We identified several compounds with highly potent antiviral activity and toxicity profiles that are superior to that of dapivirine. In particular, compound UAMC01398 is an interesting new candidate that warrants further investigation because of its superior toxicity profile and potent activity against dapivirine-resistant viruses.
Tangmunkongvorakul, Arunrat; Chariyalertsak, Suwat; Amico, K Rivet; Guptarak, Marisa; Saokhieo, Pongpun; Sangangamsakun, Thirayut; Songsupa, Radchanok; McMahan, Vanessa; Grant, Robert
This study aimed to gain a better understanding of the association between participation in a blinded antiretroviral pre-exposure prophylaxis (PrEP) clinical trial and sexual practices among men who have sex with men and transgender women. This study utilized both quantitative and qualitative methodologies. Data included reported PrEP medication adherence and sexual behavior among 114 study participants. Forty-six participants took part in qualitative data collection, 32 were interviewed and 14 participated in one of three focus group discussions. The average percentage of study medication adherence, number of sex partners and rates of sex without a condom were calculated. For qualitative data, content analysis was used to identify repeated normative themes, some of which arose spontaneously from interview interactions. Participants at the Chiang Mai site reported good adherence to the study medication. The sexual risk behavior of these participants had decreased by their final study visit; this was unrelated to level of adherence. Qualitative findings describe sexual practices that were highly contextual; participants used risk assessments to determine sex practices. Condoms were used with casual partners but not necessarily with primary partners. Our findings suggest that while PrEP is an exciting new development for HIV prevention, it must be paired with behavioral interventions to fully address sexual risk among this population. Interventions should provide this population with skills to negotiate condom use with their primary partners as well as in situations in which their sexual partners do not support condom use.
Gamarel, Kristi E; Golub, Sarit A
In the USA, men who have sex with men (MSM) in primary partnerships are at elevated risk for human immunodeficiency virus (HIV) infection. Pre-exposure prophylaxis (PrEP), a new biomedical prevention strategy, has potential to reduce HIV transmission. This study examined predictors of PrEP adoption intentions among HIV-negative MSM in primary partnerships. The sample included HIV-negative MSM (n = 164) who participated in an ongoing cross-sectional study with an in-person interview examining PrEP adoption intentions. Higher HIV risk perception, intimacy motivations for condomless sex, recent condomless anal sex with outside partners, education, and age were each independently associated with PrEP adoption intentions. In a multivariate model, only age, education, and intimacy motivations for condomless sex were significantly associated with PrEP adoption intentions. Intimacy motivations may play a central role in PrEP adoption for MSM couples. Incorporating relationship dynamics into biomedical strategies is a promising avenue for research and intervention.
Brooks, Ronald A; Landovitz, Raphael J; Regan, Rotrease; Lee, Sung-Jae; Allen, Vincent C
This study assessed perceptions of pre-exposure prophylaxis (PrEP) and their association with PrEP adoption intention among a convenience sample of 224 low socioeconomic status black men who have sex with men (BMSM) residing in Los Angeles. Participants received educational information about PrEP and completed an in-person interview. More than half (60%) of the participants indicated a high intention to adopt PrEP. Younger BMSM (18-29 years) were twice as likely to report a high intention to adopt PrEP compared to older BMSM (30+ years). Only 33% of participants were aware of PrEP and no participant had ever used PrEP. Negative perceptions were associated with a lower PrEP adoption intention and included being uncomfortable taking an HIV medicine when HIV-negative and not knowing if there are long-term side effects of taking an HIV medication. These findings suggest that BMSM may adopt PrEP but that negative perceptions may limit its uptake among this population. In order to facilitate PrEP adoption among BMSM targeted educational and community awareness programmes are needed to provide accurate information on the benefits of PrEP and to address the negative perceptions of PrEP held by local BMSM populations. © The Author(s) 2015.
Full Text Available The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP guidelines in June 2012 for men who have sex with men (MSM who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines.
Myers, Julie E.; Kurth, Ann E.; Cohen, Stephanie E.; Mannheimer, Sharon B.; Simmons, Janie; Pouget, Enrique R.; Trabold, Nicole; Haberer, Jessica E.
Abstract Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP—injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. PMID:25045996
Reyniers, Thijs; Hoornenborg, Elske; Vuylsteke, Bea; Wouters, Kristien; Laga, Marie
In many Western countries with good coverage of antiretroviral treatment (ART) programmes the annual number of HIV infections is still high and not (yet) declining among men who have sex with men (MSM). This might indicate that antiretroviral treatment roll-out alone will not turn around the course of the epidemic and that new, additional tools are needed. Antiretrovirals used as prevention tools for people not yet infected with HIV, such as pre-exposure prophylaxis (PrEP) could be such important additional tools. PrEP is a new type of biomedical prevention, which involves the use of antiretrovirals before, during and after (periods of) sexual exposure to HIV. In this review, we will focus on PrEP as a new prevention tool for MSM at high risk in Europe, including its evidence for effectiveness, challenges for implementation, ongoing European demonstration studies; as well as how PrEP relates to other existing prevention tools. In light of European Medicines Agency's recent recommendation for approval of PrEP we briefly review the potential implications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Wang, Zixin; Lau, Joseph T F; Yang, Xueying; Cai, Yong; Gross, Danielle L; Ma, Tiecheng; Liu, Yan
This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.
Rebe, Kevin; Venter, Francois; Maartens, Gary; Moorhouse, Michelle; Conradie, Francesca; Wallis, Carole; Black, Vivian; Harley, Beth; Eakles, Robyn
The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men (MSM) who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO) Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines. PMID:29568613
Kuhns, Lisa M; Hotton, Anna L; Schneider, John; Garofalo, Robert; Fujimoto, Kayo
Pre-exposure prophylaxis (PrEP) is efficacious to prevent HIV infection, however, uptake among young men who have sex with men (YMSM) is relatively low. The purpose of this study was to describe PrEP use and related factors in a representative sample of YMSM in two cities, Chicago and Houston. YMSM, ages 16-29, were recruited via respondent-driven sampling (RDS) from 2014 to 2016. Correlates of PrEP uptake were assessed in weighted multivariable logistic regression models. A total of 12.2% of participants (of 394) reported ever taking PrEP; Black YMSM had the lowest rates of uptake (4.7%) and Whites the highest (29.5%). In a multivariable regression model, having an HIV positive sex partner, reporting recent group sex, peer network size, and city (Chicago) were significantly and positively associated with use of PrEP, while Black race was negatively associated with it. Given evidence of racial/ethnic disparities in PrEP uptake in this study, further research is needed to identify potential mechanisms of action and points of intervention.
Adams, Leah M; Balderson, Benjamin H
Pre-exposure prophylaxis (PrEP), the antiretroviral treatment regimen for HIV-negative people at high risk of acquiring HIV, has demonstrated efficacy across clinical trials in several patient populations. The Centers for Disease Control (CDC) have released detailed guidelines to aid providers in prescribing PrEP for their high-risk patients, including men who have sex with men (MSM), high-risk heterosexuals, and injection drug users (IDUs). Given that much attention in PrEP has focused on MSM patients, the present study used an online survey to assess factors involved in HIV care providers' (n = 363) decisions about prescribing PrEP, along with their willingness to prescribe PrEP to patients from various risk populations (e.g., MSM, heterosexuals, IDUs). The efficacy of PrEP was an important factor in providers' decisions about prescribing PrEP, as were considerations about patients' adherence to the regimen, regular follow-up for care, and medication costs. This survey's findings also suggest that providers' willingness to prescribe PrEP varies by patient group, with providers most willing to initiate the regimen with MSM who have an HIV-positive partner, and least willing to prescribe to high-risk heterosexuals or IDUs. In the context of the current CDC recommendations for PrEP that include MSM, heterosexuals, and IDUs, examining providers' rationales for and barriers against supporting this HIV prevention strategy across patient groups merits further attention.
Page, Kimberly; Tsui, Judith; Maher, Lisa; Choopanya, Kachit; Vanichseni, Suphak; Mock, Philip A; Celum, Connie; Martin, Michael
Women who inject drugs (WWID) are at higher risk of HIV compared with their male counterparts as a result of multiple factors, including biological, behavioral, and sociostructural factors, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this article, we discuss the need for expanded prevention interventions for WWID, focusing on 2 safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). Although both interventions are well researched, they have not been well examined in the context of gender. We discuss the drivers of women injectors' higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for WWID. There is substantial potential for impact of OAT and PrEP programs for WWID in the context of broader gender-responsive HIV prevention initiatives. Although awaiting efficacy data on other biomedical approaches in the HIV prevention research "pipeline," we propose that the scale-up and implementation of these proven, safe, and effective interventions are needed now.
C Preston Neff
Full Text Available Sexual HIV-1 transmission by vaginal route is the most predominant mode of viral transmission, resulting in millions of new infections every year. In the absence of an effective vaccine, there is an urgent need to develop other alternative methods of pre-exposure prophylaxis (PrEP. Many novel drugs that are currently approved for clinical use also show great potential to prevent viral sexual transmission when administered systemically. A small animal model that permits rapid preclinical evaluation of potential candidates for their systemic PrEP efficacy will greatly enhance progress in this area of investigation. We have previously shown that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and displays CD4 T cell loss typical to that seen in the human. Thus far systemic PrEP studies have been primarily limited to RT inhibitors exemplified by tenofovir and emtricitabine. In these proof-of-concept studies we evaluated two new classes of clinically approved drugs with different modes of action namely, an integrase inhibitor raltegravir and a CCR5 inhibitor maraviroc as potential systemically administered chemo-prophylactics. Our results showed that oral administration of either of these drugs fully protects against vaginal HIV-1 challenge in the RAG-hu mouse model. Based on these results both these drugs show great promise for further development as orally administered PrEPs.
Al-Tayyib, Alia A.; Thrun, Mark W.; Haukoos, Jason S.; Walls, N. Eugene
As part of the National HIV Behavioral Surveillance System among men who have sex with men (MSM) in Denver, Colorado, we assessed knowledge of pre-exposure prophylaxis (PrEP); willingness to use PrEP; and potential changes in risk behaviors among HIV-negative participants reporting sexual activity with a male partner in the preceding 12 months. We examined knowledge of PrEP before (2008) and after (2011) results of the iPrEx trial were available. Of the 425 participants in the 2008 sample, 91 (21 %) were aware of PrEP compared to 131 (28 %) of the 461 participants in the 2011 sample (adjusted prevalence ratio: 1.43, 95 % confidence interval: 1.18, 1.72). Despite the increase in 2011, few MSM in Denver were aware of PrEP. Educating high-risk MSM about the potential utility of PrEP as an adjunct to other effective prevention methods is needed when considering the addition of PrEP to the HIV prevention arsenal. PMID:23824227
Hubach, Randolph D; Currin, Joseph M; Sanders, Carissa A; Durham, André R; Kavanaugh, Katherine E; Wheeler, Denna L; Croff, Julie M
Biomedical intervention approaches, including antiretroviral pre-exposure prophylaxis (PrEP), have been demonstrated to reduce HIV incidence among several at-risk populations and to be cost effective. However, there is limited understanding of PrEP access and uptake among men who have sex with men (MSM) residing in relatively rural states. Twenty semistructured interviews were conducted (August-November 2016) to assess opinions of and perceived barriers to accessing and adopting PrEP among MSM residing in Oklahoma. Participants perceived substantial barriers to accessing PrEP including a stigmatizing environment and less access to quality, LGBT-sensitive medical care. Overall, geographic isolation limits access to health providers and resources that support sexual health for Oklahoma MSM. Addressing stigma situated across ecological levels in an effort to increase adoption of PrEP by MSM residing in rural states remains necessary. Without this, social determinants may continue to negatively influence PrEP adoption and sexual health outcomes.
Hoagland, Brenda; De Boni, Raquel B; Moreira, Ronaldo I; Madruga, José Valdez; Kallas, Esper G; Goulart, Silvia Pereira; Cerqueira, Natalia; Torres, Thiago S; Luz, Paula M; Fernandes, Nilo Martinez; Liu, Albert Y; Grinsztejn, Beatriz; Veloso, Valdilea G
Antiretroviral pre-exposure prophylaxis (PrEP) is recommended to prevent HIV infection among high-risk men who have sex with men (MSM) though not available in Brazil where the HIV epidemic persists unabated in this group. This cross-sectional study describes PrEP awareness and willingness and associated factors among MSM and transvestite/transgender women (trans women) pre-screened for the PrEP Brasil study. Awareness was reported by 61.3 % of the participants and was associated with age, education, site, study period and prior HIV testing. Most participants (82.1 %) were willing to use PrEP, which was associated with site, study period, number of male condomless anal sexual partners and anal sex with HIV positive/unknown partners. PrEP information is need among young and less educated individuals. Willingness to use PrEP was high and future studies should be conducted to confirm PrEP acceptability and the characteristics of the population who chose to adopt this intervention.
Witzel, T Charles; Nutland, Will; Bourne, Adam
Black men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared to other MSM, despite similar levels of condom use and testing. Pre-exposure prophylaxis (PrEP) could be a useful intervention to reduce these inequalities. This research therefore aims to understand the dimensions of acceptability of a potential PrEP service for BMSM aged 18-45 years in London. In-depth semi-structured interviews were conducted with 25 PrEP-eligible BMSM between April and August 2016. Interviews were recorded and transcribed verbatim, then subject to a thematic framework analysis, informed by intersectionality theory. BMSM had distinct preferences for sexual health services, which have implications for PrEP service development. Three primary domains emerged in our analysis: proximity and anonymity; quality, efficiency and reassurance; and understanding, empathy and identity. These relate, respectively, to preferences regarding clinic location and divisions from community, features of service delivery and staff characteristics. Due to concerns about confidentiality, community-based services may not be useful for this group. Careful consideration in regards to components used in service development will facilitate ongoing engagement. Interpersonal skills of staff are central to service acceptability, particularly when staff are perceived to be from similar cultural backgrounds as their patients.
Mugo, Peter Mwangi; Sanders, Eduard J; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R; Priddy, Frances H; Haberer, Jessica E
A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.
Thomann, Matthew; Grosso, Ashley; Zapata, Richard; Chiasson, Mary Ann
In the USA, gay and other men who have sex with men and transgender women are disproportionately affected by HIV. Uptake of pre-exposure prophylaxis (PrEP), anti-retroviral therapy to prevent HIV-negative individuals from seroconverting if exposed to HIV, by members of this population remains low, particularly among African-Americans. We conducted two focus groups to assess responses to an online social media campaign focusing on PrEP use in New York City. We designed, produced and disseminated the campaign to address knowledge of PrEP; its physical and psychological side effects; and psychosocial barriers related to PrEP adherence and sex shaming. Focus group participants demonstrated a relatively high knowledge of PrEP, although considerable concern remained about side effects, particularly among Black participants. Participants suggested that stigma against PrEP users was declining as PrEP use became more common, but stigma remained, particularly for those not using condoms. Many focus group participants reported distrust of medical providers and were critical of the commodification of HIV prevention by the pharmaceutical industry. Participants reported that those in romantic relationships confronted unique issues regarding PrEP, namely suspicions of infidelity. Finally, Black participants spoke of the need for more tailored and sensitive representations of Black gay men in future programmes and interventions.
Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya
PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. The O2O model was piloted by Adam's Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant's socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0-7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14-4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19-3.54; p = 0.009), being aware of sexual partners' HIV status (OR 2.37, 95%CI 1.29-4.35; p = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19-5.09; p = 0.01), and enrolment at Adam's Love clinic compared to the other three sites
Garcia, Jonathan; Colson, Paul W.; Parker, Caroline; Hirsch, Jennifer S.
Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial dr...
Ross, Ian; Mejia, Carlos; Melendez, Johanna; Chan, Philip A; Nunn, Amy C; Powderly, William; Goodenberger, Katherine; Liu, Jingxia; Mayer, Kenneth H; Patel, Rupa R
HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for
Beymer, Matthew R; Weiss, Robert E; Sugar, Catherine A; Bourque, Linda B; Gee, Gilbert C; Morisky, Donald E; Shu, Suzanne B; Javanbakht, Marjan; Bolan, Robert K
Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying PrEP candidates may not be specific enough to identify gay, bisexual, and other men who have sex with men (MSM) at the highest risk for HIV infection. We created an HIV risk score for HIV-negative MSM based on Syndemics Theory to develop a more targeted criterion for assessing PrEP candidacy. Behavioral risk assessment and HIV testing data were analyzed for HIV-negative MSM attending the Los Angeles LGBT Center between January 2009 and June 2014 (n = 9481). Syndemics Theory informed the selection of variables for a multivariable Cox proportional hazards model. Estimated coefficients were summed to create an HIV risk score, and model fit was compared between our model and CDC guidelines using the Akaike Information Criterion and Bayesian Information Criterion. Approximately 51% of MSM were above a cutpoint that we chose as an illustrative risk score to qualify for PrEP, identifying 75% of all seroconverting MSM. Our model demonstrated a better overall fit when compared with the CDC guidelines (Akaike Information Criterion Difference = 68) in addition to identifying a greater proportion of HIV infections. Current CDC PrEP guidelines should be expanded to incorporate substance use, partner-level, and other Syndemic variables that have been shown to contribute to HIV acquisition. Deployment of such personalized algorithms may better hone PrEP criteria and allow providers and their patients to make a more informed decision prior to PrEP use.
Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R; Bukusi, Elizabeth A; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E; Ware, Norma C; Wyatt, Monique A; Marzinke, Mark A; Frenkel, Lisa M; Celum, Connie; Baeten, Jared M
Introduction : Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV. Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered. Methods : We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa. The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results : We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, pproject for African HIV-negative individuals whose partners were known to be living with HIV. Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.
van der Straten, Ariane; Stadler, Jonathan; Montgomery, Elizabeth; Hartmann, Miriam; Magazi, Busiswe; Mathebula, Florence; Schwartz, Katie; Laborde, Nicole; Soto-Torres, Lydia
Background In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants’ experience of daily vaginal gel and oral tablet regimens in VOICE. Methods In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis. Results Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support–from partners and significant others–and the relationship tradeoffs entailed by using the products appear to discourage adequate product use. Conclusions Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that
Hambrick, H Rhodes; Park, Su Hyun; Schneider, John A; Mayer, Kenneth H; Carrico, Adam W; Sherman, Scott E; Duncan, Dustin T
Men who have sex with men (MSM) commonly use inhaled nitrites, or poppers, though their use is a risk factor HIV seroconversion. Pre-exposure prophylaxis, or PrEP, is effective for HIV prevention, but is not widely used, and little is known regarding PrEP use and acceptability among MSM who use inhaled nitrites. We surveyed 580 MSM in Paris, France in 2016 about popper use, sexual behaviors including condomless anal intercourse (CAI), serosorting, and sexual positioning, PrEP use, PrEP candidacy, and interest in alternate PrEP delivery modalities. We included 444 HIV negative participants for the current study. 46.2% reported popper use in the prior 3 months. Using multivariate adjusted logistic regression, we found that popper users were more likely than non-users to consider themselves candidates for PrEP [adjusted relative risk ratio (aRRR) = 2.73; 95% CI 1.54-4.83], but they were not more likely to be current (aRRR = 1.54; 95% CI 0.71-3.33) or past (aRRR = 1.37; 95% CI 0.44-4.28) PrEP users. Mediation analyses indicated that increased CAI and serosorting partly explained the relationship between popper use and PrEP candidacy. There was considerable interest in alternate proposed PrEP delivery modalities, particularly long-acting injectable PrEP [adjusted risk ratio (aRR) = 1.43; 95% CI 1.15-1.79].
Newcomb, Michael E; Moran, Kevin; Feinstein, Brian A; Forscher, Emily; Mustanski, Brian
Young men who have sex with men (YMSM) are disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition. It remains unclear if PrEP use increases rates of condomless sex (ie, risk compensation), which may increase risk of infection if PrEP adherence is not optimal. This study aimed to examine whether PrEP use and PrEP adherence were associated with change in sexual risk behaviors in a large longitudinal cohort of YMSM reporting on multiple sexual partnerships over time. Data were obtained from the first 3 visits of an ongoing cohort study of YMSM in Chicago (analytic N = 953; 14.1% HIV-positive at baseline). Participants reported up to 4 sexual partnerships at each visit, including sexual behavior, PrEP use, and PrEP adherence within partnerships. YMSM reported higher rates of receptive condomless anal sex (CAS) in partnerships during which they were on PrEP compared with those when they were not on PrEP. This association was consistent across both HIV-negative and HIV-positive participants reporting on partnerships with both perceived HIV-negative/unknown and HIV-positive partners. The rate of receptive CAS was higher in PrEP nonadherent partnerships compared with non-PrEP partnerships. The rate of receptive CAS was also higher in PrEP nonadherent than adherent partnerships, but this was not statistically significant. These analyses provide compelling data suggesting that YMSM are engaging in risk compensation when on PrEP. If rates of receptive CAS are highest among YMSM who are PrEP nonadherent, PrEP as a prevention strategy could fail to curb HIV incidence among YMSM.
Chan, Philip A; Huang, Austin; Kantor, Rami
Tenofovir-containing regimens have demonstrated potential efficacy as pre-exposure prophylaxis (PrEP) in preventing HIV-1 infection. Transmitted drug resistance mutations associated with tenofovir, specifically the reverse transcriptase (RT) mutation K65R, may impact the effectiveness of PrEP. The worldwide prevalence of transmitted tenofovir resistance in different HIV-1 subtypes is unknown. Sequences from treatment-naïve studies and databases were aggregated and analyzed by Stanford Database tools and as per the International AIDS Society (IAS-USA) resistance criteria. RT sequences were collected from GenBank, the Stanford HIV Sequence Database and the Los Alamos HIV Sequence Database. Sequences underwent rigorous quality control measures. Tenofovir-associated resistance mutations included K65R, K70E, T69-insertion and ≥3 thymidine analogue mutations (TAMs), inclusive of M41L or L210W. A total of 19,823 sequences were evaluated across diverse HIV-1 subtypes (Subtype A: 1549 sequences, B: 9783, C: 3198, D: 483, F: 372, G: 594, H: 41, J: 69, K: 239, CRF01_AE: 1797 and CRF02_AG: 1698). Overall, tenofovir resistance prevalence was 0.4% (n=77/19,823, 95% confidence interval or CI: 0.3 to 0.5). K65R was found in 20 sequences (0.1%, 95% CI: 0.06 to 0.15). Differences in the prevalence of K65R between HIV-1 subtypes were not statistically significant. K70E and ≥3 TAMs were found in 0.015% (95% CI: 0.004 to 0.04) and 0.27% (95% CI: 0.2 to 0.4) of sequences, respectively. Prevalence of transmitted K65R and other tenofovir resistance mutations across diverse HIV-1 subtypes and recombinants is low, suggesting minimal effect on tenofovir-containing PrEP regimens.
Steven A John
Full Text Available Gay, bisexual, and other men who have sex with men (GBM are disproportionately affected by the HIV epidemic. Despite the promise of pre-exposure prophylaxis (PrEP in reducing HIV transmission risk, barriers for uptake and persistence exist. We sought to identify whether GBM in a nationwide cohort who have not yet initiated PrEP (n = 906 would prefer to get PrEP-related care from a primary care provider (PCP compared to a specialist clinic or provider. We then sought to identify their level of interest and factors associated with preference for using home-based PrEP services (i.e., HB-PrEP, defined to participants as conducting HIV/STI self-testing from home with PrEP prescription mailing after an initial in-person clinic visit. We examined the associations of demographics, sexual HIV transmission risk, concern about frequent medical checkups associated with PrEP, health care access, and PrEP intentions with preferences for healthcare provider type and HB-PrEP. Concern about frequent medical checkups were associated with preferring a PCP for PrEP-related care, but men who perceived a barrier to bringing up the topic of PrEP with a doctor preferred a specialist clinic or provider more than a PCP. HB-PrEP was more appealing for younger men and those engaged in sexual HIV transmission risk, suggesting HB-PrEP could help reach GBM most vulnerable to HIV and in need of PrEP. HB-PrEP expansion has potential to increase PrEP uptake and persistence among GBM, particularly for men with barriers to clinic-based care and higher intentions to initiate PrEP. Clinical guidelines regarding HB-PrEP are needed to expand its use.
Kovarova, Martina; Shanmugasundaram, Uma; Baker, Caroline E; Spagnuolo, Rae Ann; De, Chandrav; Nixon, Christopher C; Wahl, Angela; Garcia, J Victor
Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers highlight that HIV acquisition is a major health concern for women and children globally. They also emphasize the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with low cytotoxicity, was administered orally to NOD/SCID/γc -/- mice and to bone marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection. HIV inhibitory activity in serum, cervicovaginal secretions and saliva was evaluated 4 h after administration. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine's ability to prevent vaginal and oral HIV transmission was evaluated using highly relevant transmitted/founder viruses in BLT mice. Strong HIV inhibitory activity in serum, cervicovaginal secretions and saliva obtained from animals after a single oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (10 mg/kg) demonstrated efficient drug penetration into relevant mucosal sites. A single daily oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine resulted in efficient prevention of vaginal and oral HIV transmission after multiple high-dose exposures to transmitted/founder viruses in BLT humanized mice. Our data demonstrated that 4'-ethynyl-2-fluoro-2'-deoxyadenosine efficiently prevents both vaginal and oral HIV transmission. Together with 4'-ethynyl-2-fluoro-2'-deoxyadenosine's relatively low toxicity and high potency against drug-resistant HIV strains, these data support further clinical development of 4'-ethynyl-2-fluoro-2'-deoxyadenosine as a potential pre-exposure prophylaxis agent to prevent HIV transmission in women and their infants. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial
Reza-Paul, Sushena; Lazarus, Lisa; Doshi, Monika; Hafeez Ur Rahman, Syed; Ramaiah, Manjula; Maiya, Raviprakash; Ms, Venugopal; Venukumar, K T; Sundararaman, Sundar; Becker, Marissa; Moses, Stephen; Lorway, Robert
HIV prevalence among female sex workers (FSWs) in India remains well above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka. From January-April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data. Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a "double safety" in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95%) expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%), those who do not use condoms when clients offer more money (58%), who do not consistently use condoms with regular partners (57%), who drink alcohol regularly (49%), and who do not use condoms consistently with clients (48%). This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means of
Solomon, Marc M; Schechter, Mauro; Liu, Albert Y; McMahan, Vanessa M; Guanira, Juan V; Hance, Robert J; Chariyalertsak, Suwat; Mayer, Kenneth H; Grant, Robert M
Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.
Schechter, Mauro; Liu, Albert Y.; McManhan, Vanessa M.; Guanira, Juan V.; Hance, Robert J.; Chariyalertsak, Suwat; Mayer, Kenneth H.; Grant, Robert M.
Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. Methods: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Results: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. Conclusions: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered. PMID:26413853
Full Text Available To investigate the awareness of, and willingness to use, HIV Pre-Exposure Prophylaxis (PrEP, and willingness to take part in a PrEP study among gay and bisexual men in Scotland.Cross-sectional survey of 17 gay commercial venues in Glasgow and Edinburgh in May 2011 (N = 1515, 65.2% response rate; 1393 are included in the analyses.Just under one-third of participants had heard of PrEP (n = 434; 31.2%, with awareness associated with being aged older than 35 years, talking to UAI partners about HIV, and with having had an HIV or STI test in the previous 12 months. Around half were willing to take part in a PrEP study (n = 695; 49.9% or to take PrEP on a daily basis (n = 756; 54.3%. In multivariate analysis, willingness to take PrEP was associated with lower levels of education, regular gay scene attendance, 'high-risk' unprotected anal intercourse (UAI and testing for HIV or STI in the previous 12 months. Reasons for not wanting to participate in a PrEP study or take PrEP included perceptions of low personal risk of HIV and concerns with using medication as an HIV prevention method.There is a willingness to engage in new forms of HIV prevention and research amongst a significant number of gay and bisexual men in Scotland. Future biomedical HIV interventions need to consider the links between sexual risk behaviour, testing, and potential PrEP use.
Parker, Caroline M.; Parker, Richard G.; Wilson, Patrick A.; Garcia, Jonathan; Hirsch, Jennifer S.
Abstract Research has demonstrated the clinical effectiveness of pre-exposure prophylaxis (PrEP) for HIV prevention, but little is known about how factors at the individual-, interpersonal-, community-, and structural levels impact PrEP use for black men who have sex with men (BMSM). We advance existing work by examining how all levels of the ecological framework must be addressed for PrEP to be successfully implemented as an effective HIV prevention approach. We interviewed 31 BMSM three times each and 17 community stakeholders once each; interviews were taped, transcribed, and analyzed using the constant comparative method. Factors that influence how BMSM experienced PrEP emerged across all levels of the ecological framework: At the individual level, respondents were wary of giving medication to healthy people and of the potential side-effects. At the interpersonal level, BMSM believed that PrEP use would discourage condom use and that PrEP should only be one option for HIV prevention, not the main option. At the community level, men described not trusting the pharmaceutical industry and described PrEP as an option for others, not for themselves. At the structural level, BMSM talked about HIV and sexuality-related stigmas and how they must overcome those before PrEP engagement. BMSM are a key population in the US National HIV/AIDS Strategy, yet few individuals believe that PrEP would be personally helpful. Our research indicates the urgent need to raise awareness and address structural stigma and policies that could be substantial barriers to the scale-up and implementation of PrEP-related services. PMID:27220036
Full Text Available BACKGROUND: Oral pre-exposure prophylaxis (PrEP can be clinically effective and cost-effective for HIV prevention in high-risk men who have sex with men (MSM. However, individual patients have different risk profiles, real-world populations vary, and no practical tools exist to guide clinical decisions or public health strategies. We introduce a practical model of HIV acquisition, including both a personalized risk calculator for clinical management and a cost-effectiveness calculator for population-level decisions. METHODS: We developed a decision-analytic model of PrEP for MSM. The primary clinical effectiveness and cost-effectiveness outcomes were the number needed to treat (NNT to prevent one HIV infection, and the cost per quality-adjusted life-year (QALY gained. We characterized patients according to risk factors including PrEP adherence, condom use, sexual frequency, background HIV prevalence and antiretroviral therapy use. RESULTS: With standard PrEP adherence and national epidemiologic parameters, the estimated NNT was 64 (95% uncertainty range: 26, 176 at a cost of $160,000 (cost saving, $740,000 per QALY--comparable to other published models. With high (35% HIV prevalence, the NNT was 35 (21, 57, and cost per QALY was $27,000 (cost saving, $160,000, and with high PrEP adherence, the NNT was 30 (14, 69, and cost per QALY was $3,000 (cost saving, $200,000. In contrast, for monogamous, serodiscordant relationships with partner antiretroviral therapy use, the NNT was 90 (39, 157 and cost per QALY was $280,000 ($14,000, $670,000. CONCLUSIONS: PrEP results vary widely across individuals and populations. Risk calculators may aid in patient education, clinical decision-making, and cost-effectiveness evaluation.
Kalichman, Seth C; Eaton, Lisa
Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. HIV-negative sexually active men who have sex with men ( N = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs. A total of 118 (43%) men surveyed had two or more male sex partners and condomless anal sex in the previous six months. Alcohol use was reported by over 90% of men and it was common for participants to believe that mixing alcohol and antiretrovirals is toxic; 75% endorsed at least one interactive toxicity belief. Among the 118 men who had engaged in condomless anal sex and had multiple sex partners, one in three stated that they were not interested in PrEP and men not interested in PrEP were significantly more likely to binge drink and hold interactive toxicity beliefs. These results mirror studies that find interactive toxicity beliefs are a potent predictor of intentional antiretroviral non-adherence among people living with HIV and suggest interactive toxicity beliefs may impede PrEP uptake and adherence. Messages to increase PrEP awareness and adherence may also take steps to counter erroneous beliefs about mixing alcohol with antiretrovirals in the context of PrEP.
Govender, Eliza M; Mansoor, Leila E; Abdool Karim, Quarraisha
Young women bear a disproportionately high burden of HIV infection in sub-Saharan Africa, prioritising pre-exposure prophylaxis (PrEP) can be an integral part of HIV prevention combination strategies. Women initiated HIV prevention technology options will require consistent adherence, an imperative for product effectiveness. With several PrEP clinical trials underway; exploring women's acceptability to advances in HIV prevention technologies can better facilitate demand creation for future PrEP roll out. This study utilised the opportunity of post-trial access to CAPRISA 008 women (trial) and non-trial women from three geo-spatial settings (urban, rural and peri-urban) to identify microbicide acceptability and how product associations of microbicides can influence future HIV prevention choices. Six participatory workshops using participatory action research with art-based activities and discussion groups were conducted in KwaZulu-Natal with 104 women from various geo-spatial locations and social status to understand microbicide acceptability and product associations. The data were analysed using thematic analysis. The study found that women's acceptability and product association of the tenofovir gel microbicide differed according to rural and urban areas. Most urban women identified confidence, sexiness and classiness as key associations that will encourage microbicide acceptability and use, while rural women identified respect, responsibility and confidence as the key product associations, with increased focus on the individual and collective family/community benefits of product acceptance and use. Urban-rural differences suggest a market segmentation that is contextualised to be locally responsive to promote HIV prevention technologies. Various sexual encounters further determined the types of HIV prevention technologies women would consider. In line with WHO's recommendation that PrEP should be an additional prevention choice for people at risk of HIV, this
Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E
Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.
Morton, Jennifer F; Celum, Connie; Njoroge, John; Nakyanzi, Agnes; Wakhungu, Imeldah; Tindimwebwa, Edna; Ongachi, Snaidah; Sedah, Eric; Okwero, Emmanuel; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Haberer, Jessica E; Baeten, Jared M; Heffron, Renee
For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach. Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partner's first 6 months of ART use. We conducted individual and group discussions with counseling staff to elicit the health communication framework and key messages about ART and PrEP that were delivered to couples. Counseling sessions for serodiscordant couples about PrEP and ART included discussions of HIV serodiscordance, PrEP and ART initiation and integrated use, and PrEP discontinuation. ART messages emphasized daily, lifelong use for treatment and prevention, adherence, viral suppression, resistance, side effects, and safety of ART during pregnancy. PrEP messages emphasized daily dosing, time-limited PrEP use until the HIV-positive partner sustained 6 months of high adherence to ART, adherence, safety during conception, side effects, and other risks for HIV. Counseling messages for HIV-serodiscordant couples are integral to the delivery of time-limited PrEP as a "bridge" to ART-driven viral suppression. Their incorporation into programmatic scale-up will maximize intervention impact on the global epidemic.
Ding, Yingying; Yan, Huamei; Ning, Zhen; Cai, Xiaofeng; Yang, Yin; Pan, Rong; Zhou, Yanqiu; Zheng, Huang; Gao, Meiyang; Rou, Keming; Wu, Zunyou; He, Na
Little is known about the acceptance and actual uptake of pre-exposure prophylaxis (PrEP) and associated factors in men who have sex with men (MSM) in China. This study is the baseline survey of an intervention study designed to evaluate the effectiveness of tenofovirdisoproxil fumarate (TDF) on a daily use for human immunodeficiency virus (HIV) prevention among MSM in Shanghai, China. From October 2012 to December 2013, a total of 1,033 MSM in Shanghai were recruited by local district Centers for Disease Control and Prevention (CDC) and a MSM community-based non-governmental organization (NGO). Among them, 197 (19.1%) participants expressed willingness to use the TDF group at baseline survey, but only 26 (2.5%) participated in the TDF group and took TDF one tablet a day. Higher willingness to use PrEP was associated with being 45 years or older, non-local residents, having more male sex partners in the past 6 months and not using condom at last anal sex with man. Acutal uptake of PrEP was associated with having ≥ 11 male sex partners in lifetime and reporting no female sex partners in lifetime. Reasons for not participating in TDF group among those who expressed willingness to use PrEP at baseline survey included loss of contact, ineligiblity because of abnormal results for liver or renal function tests, change of mind, and HIV seroconversion before uptake of PrEP. Our findings suggest that promotion of PrEP in MSM remains challenging at current circumstancein China. Future research is needed to solicit effective education and intervention programs to promote acceptance of PrEP among Chinese MSM.
Galindo Gabriel R
Full Text Available Abstract Background An international randomized clinical trial (RCT on pre-exposure prophylaxis (PrEP as an human immunodeficiency virus (HIV-prevention intervention found that taken on a daily basis, PrEP was safe and effective among men who have sex with men (MSM and male-to-female transgender women. Within the context of the HIV epidemic in the United States (US, MSM and transgender women are the most appropriate groups to target for PrEP implementation at the population level; however, their perspectives on evidenced-based biomedical research and the results of this large trial remain virtually unknown. In this study, we examined the acceptability of individual daily use of PrEP and assessed potential barriers to community uptake. Methods We conducted semi-structured interviews with an ethnoracially diverse sample of thirty HIV-negative and unknown status MSM (n = 24 and transgender women (n = 6 in three California metropolitan areas. Given the burden of disease among ethnoracial minorities in the US, we purposefully oversampled for these groups. Thematic coding and analysis of data was conducted utilizing an approach rooted in grounded theory. Results While participants expressed general interest in PrEP availability, results demonstrate: a lack of community awareness and confusion about PrEP; reservations about PrEP utilization, even when informed of efficacious RCT results; and concerns regarding equity and the manner in which a PrEP intervention could be packaged and marketed in their communities. Conclusions In order to effectively reduce HIV health disparities at the population level, PrEP implementation must take into account the uptake concerns of those groups who would actually access and use this biomedical intervention as a prevention strategy. Recommendations addressing these concerns are provided.
Full Text Available HIV Pre-Exposure Prophylaxis (PrEP has been found to be efficacious in preventing HIV acquisition among seronegative individuals in a variety of risk groups, including men who have sex with men and people who inject drugs. To date, however, it remains unclear how socio-cultural norms (e.g., attitudes towards HIV; social understandings regarding HIV risk practices may influence the scalability of future PrEP interventions. The objective of this study is to assess how socio-cultural norms may influence the implementation and scalability of future HIV PrEP interventions in Vancouver, Canada.We conducted 50 interviews with young men (ages 18-24 with a variety of HIV risk behavioural profiles (e.g., young men who inject drugs; MSM. Interviews focused on participants' experiences and perceptions with various HIV interventions and policies, including PrEP.While awareness of PrEP was generally low, perceptions about the potential personal and public health gains associated with PrEP were interconnected with expressions of complex and sometimes conflicting social norms. Some accounts characterized PrEP as a convenient form of reliable protection against HIV, likening it to the female birth control pill. Other accounts cast PrEP as a means to facilitate 'socially unacceptable' behaviour (e.g., promiscuity. Stigmatizing rhetoric was used to position PrEP as a tool that could promote some groups' proclivities to take 'risks'.Stigma regarding 'risky' behaviour and PrEP should not be underestimated as a serious implementation challenge. Pre-implementation strategies that concomitantly aim to improve knowledge about PrEP, while addressing associated social prejudices, may be key to effective implementation and scale-up.
Full Text Available In many settings, interventions targeting female sex workers (FSWs could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use—one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed ‘pimps’ was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used.
Walters, Suzan M; Reilly, Kathleen H; Neaigus, Alan; Braunstein, Sarah
Women who inject drugs (WWID) are at heightened risk for HIV due to biological, behavioral, and structural factors. Pre-exposure prophylaxis (PrEP) could aid in HIV prevention for WWID. However, little is known about WWID awareness of PrEP, which is a necessary step that must occur before PrEP uptake. We report factors associated with greater awareness among WWID to identify efficient means of awareness dissemination. Data from the 2015 National HIV Behavioral Surveillance (NHBS) system cycle on injection drug use collected in New York City (NYC) were used. Bivariable analyses, using chi-squared statistics, were conducted to examine correlates of awareness of PrEP with socio-demographic, behavioral, and health care variables. Multivariable logistic regression was used to estimate adjusted associations and determine differences in awareness of PrEP. The analysis consisted of 118 WWID. Awareness of PrEP was relatively low (31%), and risk factors were high. In the last 12 months, almost two thirds (65%) reported condomless sex, approximately one third (31%) reported transactional sex, and one third (32%) reported sharing injection equipment. In multivariable logistic regression, increased PrEP awareness was associated with reported transactional sex (AOR 3.32, 95% CI 1.22-9.00) and having a conversation about HIV prevention at a syringe exchange program (SEP) (AOR 7.61, 95% CI 2.65-21.84). We did not find race, education, household income, age, binge drinking, or sexual identity to be significantly associated with PrEP awareness. Large proportions of WWID were unaware of PrEP. These findings suggest that social networks (specifically sex work and SEP networks) are an efficient means for disseminating messaging about prevention materials such as PrEP. We recommend that SEP access increase, SEP processes be adopted in other health care settings, and WWID networks be utilized to increase PrEP awareness.
Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.
Silapaswan, Andrew; Krakower, Douglas; Mayer, Kenneth H
Since FDA approval of HIV pre-exposure prophylaxis (PrEP) for HIV prevention, attention has been focused on PrEP implementation. The CDC estimates that 1.2 million U.S. adults might benefit from PrEP, but only a minority are using PrEP, so there is a significant unmet need to increase access for those at risk for HIV. Given the large numbers of individuals who have indications for PrEP, there are not enough practicing specialists to meet the growing need for providers trained in providing PrEP. Moreover, since PrEP is a preventive intervention for otherwise healthy individuals, primary care providers (PCPs) should be primary prescribers of PrEP. There are important clinical considerations that providers should take into account when planning to prescribe PrEP, which are highlighted in the clinical case discussed. A growing body of research also suggests that some providers may be cautious about prescribing PrEP because of concerns regarding its "real-world" effectiveness, anticipated unintended consequences associated with its use, and ambiguity as to who should prescribe it. This review summarizes findings from studies that have assessed prescriber behavior regarding provision of PrEP, and offers recommendations on how to optimize PrEP implementation in primary care settings. Development and dissemination of educational interventions for PCPs and potential PrEP users are needed, including improved methods to assist clinicians in identifying appropriate PrEP candidates, and programs to promote medication adherence and access to social and behavioral health services. PCPs are well-positioned to prescribe PrEP and coordinate health-related services to improve the sexual health of their patients, but tailored educational programs are needed.
Koenig, H C; Mounzer, K; Daughtridge, G W; Sloan, C E; Lalley-Chareczko, L; Moorthy, G S; Conyngham, S C; Zuppa, A F; Montaner, L J; Tebas, P
Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real-time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. We developed a urine assay using high-performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log 10 categories between 0 and 10 000 ng/mL. We validated the assay in three cohorts: (1) HIV-positive subjects with undetectable viral loads on a TDF/FTC-based regimen, (2) healthy HIV-negative subjects who received a single dose of TDF/FTC, and (3) HIV-negative subjects receiving daily TDF/FTC as PrEP for 24 weeks. The urine assay detected TFV with greater sensitivity than plasma-based measures and with a window of measurements within 7 days of the last TDF/FTC dose. Based on the urine log-linear clearance after the last dose and its concordance with all detectable plasma levels, a urine TFV concentration > 1000 ng/mL was identified as highly predictive of the presence of TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low adherence patterns within the last 48 h (> 1000 ng/mL versus 10-1000 ng/mL), as well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to measurement. We provide proof of concept that a semiquantitative urine assay measuring levels of TFV could be further developed into a point-of-care test and be a useful tool to monitor adherence to PrEP. © 2017 British HIV Association.
Krakower, Douglas S; Ware, Norma C; Maloney, Kevin M; Wilson, Ira B; Wong, John B; Mayer, Kenneth H
The Centers for Disease Control and Prevention estimates that one in four sexually active men who have sex with men (MSM) could decrease their HIV risk by using HIV pre-exposure prophylaxis (PrEP). Because many MSM access healthcare from primary care providers (PCPs), these clinicians could play an important role in providing access to PrEP. Semistructured qualitative interviews were conducted with 31 PCPs in Boston, MA, to explore how they approach decisions about prescribing PrEP to MSM and their experiences with PrEP provision. Purposive sampling included 12 PCPs from an urban community health center specializing in the care of lesbian, gay, bisexual, and transgender persons ("LGBT specialists") and 19 PCPs from a general academic medical center ("generalists"). Analyses utilized an inductive approach to identify emergent themes. Both groups of PCPs approached prescribing decisions about PrEP as a process of informed decision-making with patients. Providers would defer to patients' preferences if they were unsure about the appropriateness of PrEP. LGBT specialists and generalists were at vastly different stages of adopting PrEP into practice. For LGBT specialists, PrEP was a disruptive innovation that rapidly became normative in practice. Generalists had limited experience with PrEP; however, they desired succinct decision-support tools to help them achieve proficiency, because they considered preventive medicine to be central to their professional role. As generalists vastly outnumber LGBT specialists in the United States, interventions to support PrEP provision by generalists could accelerate the scale-up of PrEP for MSM nationally, which could in turn decrease HIV incidence for this priority population.
Krakower, Douglas S; Maloney, Kevin M; Grasso, Chris; Melbourne, Katherine; Mayer, Kenneth H
An estimated 1.2 million Americans have indications for using antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at-risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Thirty-two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11-33). Most clinicians reported testing and risk-reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale-up of this efficacious intervention.
Brooks, Ronald A; Landovitz, Raphael J; Kaplan, Rachel L; Lieber, Eli; Lee, Sung-Jae; Barkley, Thomas W
The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.
Liu, Chunxing; Ding, Yingying; Ning, Zhen; Gao, Meiyang; Liu, Xing; Wong, Frank Y; He, Na
Pre-exposure prophylaxis (PrEP) is a biomedical approach for preventing the acquisition of HIV in populations at substantial risk for HIV. However, its uptake among men who have sex with men (MSM) is low in China. The study aimed to identify factors that might influence MSM's uptake and use of PrEP. In-depth interviews were conducted with 32 self-identified MSM from a PrEP intervention study evaluating daily oral tenofovir disoproxil fumarate (TDF) to prevent HIV infection. Of these men, 11 were presently using the 'TDF' group; 8 from the 'change-over' group (i.e. initially used PrEP but subsequently quitted); and 13 from the non-user group. Data were analysed using thematic approach. Perception of low HIV risk, mistrust of the national PrEP program, and concerns of side effects were the main reasons for not wanting to use PrEP. Also, lack of main sexual partner's support, difficulties in adhering to the daily TDF regimen, and the inconvenient schedules in securing the medicine were the major reasons for not wanting to use or quitting the use of PrEP. On the other hand, perceived high HIV risk, beliefs in efficacy of PrEP, and worries of transmitting HIV to families were the major motives for PrEP uptake. Findings suggest that PrEP implementation strategies should first address issues including but not limited to accurate self-assessment of HIV risk, mistrust and limited knowledge about medical trials and PrEP, and ease of accessing PrEP.
Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Varghese, Jarvis; Nelson, Ruban; Bharat, Shalini
This qualitative study explored the acceptability of HIV pre-exposure prophylaxis (PrEP) among MSM in India, and identified facilitators and barriers to future PrEP uptake. In 2014, we conducted 10 focus groups (n=61) among a purposive sample of diverse MSM recruited through community-based organizations in Chennai and Mumbai, and 10 key informant interviews with community leaders and health care providers. Participants' mean age was 26.1 years (SD 4.8); 62% completed secondary education, and 42% engaged in sex work. No focus group participants had heard of PrEP, but once explained, most reported they would likely use it. PrEP was alternately perceived as a 'back-up plan', a condom substitute, or a burden with concurrent condom use. Facilitators were potential for covert use, sex without condoms, and anxiety-less sex. Potential barriers emerged around stigma associated with PrEP use, fear of disclosures to one's family, wife, or male steady partner, and being labeled as HIV-positive or promiscuous by peers. Preferences emerged for intermittent rather than daily PrEP use, injectable PrEP, and free or subsidized access through community organizations or government hospitals. Key informants expressed additional concerns about risk compensation, non-adherence, and impact on ART availability for treatment. Demonstration projects are needed in India to support PrEP implementation tailored for at-risk MSM. Educational interventions for MSM should address concerns about PrEP effectiveness, side effects, and mitigate risk compensation. Community engagement may facilitate broad acceptability and challenge stigma around PrEP use. Importantly, provision of free or subsidized PrEP is necessary to making implementation feasible among low socioeconomic status MSM in India.
Background An international randomized clinical trial (RCT) on pre-exposure prophylaxis (PrEP) as an human immunodeficiency virus (HIV)-prevention intervention found that taken on a daily basis, PrEP was safe and effective among men who have sex with men (MSM) and male-to-female transgender women. Within the context of the HIV epidemic in the United States (US), MSM and transgender women are the most appropriate groups to target for PrEP implementation at the population level; however, their perspectives on evidenced-based biomedical research and the results of this large trial remain virtually unknown. In this study, we examined the acceptability of individual daily use of PrEP and assessed potential barriers to community uptake. Methods We conducted semi-structured interviews with an ethnoracially diverse sample of thirty HIV-negative and unknown status MSM (n = 24) and transgender women (n = 6) in three California metropolitan areas. Given the burden of disease among ethnoracial minorities in the US, we purposefully oversampled for these groups. Thematic coding and analysis of data was conducted utilizing an approach rooted in grounded theory. Results While participants expressed general interest in PrEP availability, results demonstrate: a lack of community awareness and confusion about PrEP; reservations about PrEP utilization, even when informed of efficacious RCT results; and concerns regarding equity and the manner in which a PrEP intervention could be packaged and marketed in their communities. Conclusions In order to effectively reduce HIV health disparities at the population level, PrEP implementation must take into account the uptake concerns of those groups who would actually access and use this biomedical intervention as a prevention strategy. Recommendations addressing these concerns are provided. PMID:23181780
Karuga, Robinson Njoroge; Njenga, Serah Nduta; Mulwa, Rueben; Kilonzo, Nduku; Bahati, Prince; O'reilley, Kevin; Gelmon, Lawrence; Mbaabu, Stephen; Wachihi, Charles; Githuka, George; Kiragu, Michael
The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.
Robinson Njoroge Karuga
Full Text Available The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention.Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55.83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price.There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.
Freeborn, Kellie; Portillo, Carmen J
Pre-exposure prophylaxis (PrEP) for HIV has been available since 2012. Even so, PrEP has not been widely accepted among healthcare providers and MSM some of whom are convinced that PrEP decreases condom use, and increases sexually transmitted infections (STIs). A systematic review of the state of the evidence regarding the association of PrEP with condom use, STI incidence and change in sexual risk behaviors in MSM. A structured search of databases resulted in 142 potential citations, but only ten publications met inclusion criteria and underwent data abstraction and critical appraisal. An adapted Cochrane Collaboration domain based assessment tool was used to critically appraise the methodological components of each quantitative study, and the Mixed Methods Appraisal Tool (MMAT) was used to critically appraise qualitative and mixed-methods studies. Condom use in MSM utilizing PrEP is influenced by multiple factors. Studies indicate rates of STIs in treatment and placebo groups were high. PrEP did not significantly change STI rates between baseline and follow-up. Reporting of sexual risk improved when questionnaires were completed in private by clients. Our review found that PrEP may provide an opportunity for MSM to access sexual health care, testing, treatment and counselling services. We did not find any conclusive evidence that PrEP users increase sexual risk behaviors. The perception among healthcare providers that PrEP leads to increased sexual risk behaviors has yet to be confirmed. In order to provide effective sexual health services, clinicians need to be knowledgeable about PrEP as an HIV prevention tool. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Gredig, Daniel; Uggowitzer, Franziska; Hassler, Benedikt; Weber, Patrick; Nideröst, Sibylle
Pre-exposure prophylaxis (PrEP) is discussed as an additional HIV prevention method targeting men who have sex with men (MSM). So far, PrEP has not been approved in Switzerland and only little is known about the acceptability of PrEP among MSM living in Switzerland. Given the slow uptake of PrEP among MSM in the USA, the objectives of the study were to investigate the acceptability for PrEP and to identify factors influencing the acceptability for this prevention method and the willingness to adopt it. During a 4-month period we conducted five focus group discussions with 23 consecutively sampled HIV-negative MSM aged 22-60 years living in Switzerland. We analyzed the data according to qualitative content analysis. The acceptability of PrEP varied considerably among the participants. Some would use PrEP immediately after its introduction in Switzerland because it provides an alternative to condoms which they are unable or unwilling to use. Others were more ambivalent towards PrEP but still considered it (1) an additional or alternative protection to regular condom use, (2) an option to engage in sexual activities with less worries and anxieties or (3) a protection during receptive anal intercourse independently of the sexual partner's protective behaviour. Some participants would not consider using PrEP at all: they do not see any benefit in PrEP as they have adopted safer sex practices and did not mention any problems with condom use. Others are still undecided and could imagine using an improved form of PrEP. The results provide a valuable basis for a model explaining the acceptability of PrEP among MSM and suggest including the personal HIV protection strategy in the considerations adopted.
Sabina S Alistar
Full Text Available 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.
Idoko, John; Folayan, Morenike Oluwatoyin; Dadem, Nancin Yusufu; Kolawole, Grace Oluwatosin; Anenih, James; Alhassan, Emmanuel
Nigeria has the second highest number of new HIV infections annually. Therefore, it is important to explore new strategies for preventing new infections. The introduction of pre-exposure prophylaxis (PrEP) for use by persons at high risk of HIV infection has new potential in preventing new HIV infections. The aim of this study is to explore the public opinion, community interest, and perceptions about the use and access to PrEP in Nigeria. This formative study used a mixed method approach to collect data on public opinions and perceptions on appropriate target groups for PrEP access, community interest, perceptions about the use of PrEP as an HIV-prevention tool, how best to communicate with participants about PrEP, concerns about PrEP use by serodiscordant couples, and suggestions for the design and implementation of a PrEP demonstration project. Telephone and in-depth interviews were conducted, and focus group discussions and consultative meetings were held with critical stakeholders engaged in HIV-prevention, treatment, care, and support programmes in Nigeria. An online survey was also conducted. HIV serodiscordant couples were identified as the appropriate target group for PrEP use. Most respondents felt that PrEP use by key affected populations would help reduce the HIV incidence. Stigma was identified as a major concern and a potential barrier for the acceptance and use of PrEP by HIV serodiscordant couples. Electronic and print media were identified as important means for massive public education to prevent stigma and create awareness about PrEP. In a male dominated society such as Nigeria, HIV-negative male partners in serodiscordant relationships may resist enrolment in PrEP programmes. This may be complicated by the fact that the identified index partner in most serodiscordant relationships in Nigeria is an HIV-positive woman, who is often diagnosed during pregnancy. PrEP uptake and use by HIV serodiscordant couples in Nigeria may face notable but
Mitchell, Jason W; Lee, Ji-Young; Woodyatt, Cory; Bauermeister, José; Sullivan, Patrick; Stephenson, Rob
One efficacious strategy to help prevent HIV is oral pre-exposure prophylaxis (PrEP), a daily regimen of antiretroviral treatment taken by HIV-negative individuals. Two of the recommendations of Centers for Disease Control and Prevention (CDC) guidelines for PrEP pertain to being in a relationship (i.e., male couples). Despite the recognition of how primary partners in male couples' relationships shape HIV risk and CDC's PrEP guidelines, there is a paucity of data that examine HIV-negative male couples' attitudes toward PrEP use and using PrEP with a sexual agreement. A sexual agreement is an explicit agreement made between two individuals about what sex and other related behaviors may occur within and outside of their relationship. In this qualitative study, we examine HIV-negative male couples' attitudes toward PrEP use and whether they thought PrEP could be integrated into a sexual agreement. Data for this study are drawn from couple-level interviews conducted in 2014 with 29 HIV-negative male couples who had a sexual agreement and were from Atlanta or Detroit. Both passive (e.g., flyers) and active (e.g., targeted Facebook advertisements) recruitment methods were used; the sample was stratified by agreement type. Thematic analysis was applied to identify the following themes regarding HIV-negative male couples' attitudes toward PrEP use: (1) PrEP and condom use; (2) concerns about PrEP (e.g., effectiveness, side effects, and promoting sexually risky behavior); and (3) accessibility of PrEP. Some thought PrEP could be a part of couples' agreement because it could help reduce sexual anxiety and sexual risk, and would help keep the couple safe. Others described PrEP use with an agreement as something for "others". Some were also concerned that incorporating PrEP could usurp the need for a sexual agreement in a couples' relationship. These themes highlight the need to improve informational messaging and promotion efforts about PrEP among HIV-negative male couples
Albert Y Liu
Full Text Available Pre-exposure prophylaxis (PrEP trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs.Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93% increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair.This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also
Stefanie J. Vaccher
Full Text Available IntroductionThe effectiveness of daily pre-exposure prophylaxis (PrEP is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM. This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project.Materials and methodsIndividuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day, event-driven (pills taken only around specific risk events, or periodic (daily dosing during periods of increased risk.ResultsOverall, 315 GBM (98% of study sample provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR = 4.58, 95% confidence intervals (95% CI: (1.68, 12.49], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76].DiscussionIndividuals’ preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to
Matthew E Levy
Full Text Available Clinical trials are currently investigating the safety and efficacy of long-acting injectable (LAI agents as HIV pre-exposure prophylaxis (PrEP. Using National HIV Behavioral Surveillance data, we assessed the self-reported willingness of men who have sex with men (MSM to use LAI PrEP and their preference for LAI versus daily oral PrEP.In 2014, venue-based sampling was used to recruit MSM aged ≥18 years in Washington, DC. Participants completed an interviewer-administered survey followed by voluntary HIV testing. This analysis included MSM who self-reported negative/unknown HIV status at study entry. Correlates of being "very likely" to use LAI PrEP and preferring it to daily oral PrEP were identified using multivariable logistic regression.Of 314 participants who self-reported negative/unknown HIV status, 50% were <30 years old, 41% were non-Hispanic Black, 37% were non-Hispanic White, and 14% were Hispanic. If LAI PrEP were offered for free or covered by health insurance, 62% were very likely, 25% were somewhat likely, and 12% were unlikely to use it. Regarding preferred PrEP modality, 67% chose LAI PrEP, 24% chose oral PrEP, and 9% chose neither. Correlates of being very likely versus somewhat likely/unlikely to use LAI PrEP included age <30 years (aOR 1.64; 95% CI 1.00-2.68, reporting ≥6 (vs. 1 sex partners in the last year (aOR 2.60; 95% CI 1.22-5.53, previous oral PrEP use (aOR 3.67; 95% CI 1.20-11.24, and being newly identified as HIV-infected during study testing (aOR 4.83; 95% CI 1.03-22.67. Black (vs. White men (aOR 0.48; 95% CI 0.24-0.96 and men with an income of <$20,000 (vs. ≥$75,000; aOR 0.37; 95% CI 0.15-0.93 were less likely to prefer LAI to oral PrEP.If LAI PrEP were found to be efficacious, its addition to the HIV prevention toolkit could facilitate more complete PrEP coverage among MSM at risk for HIV.
Oldenburg, Catherine E; Le, Bao; Huyen, Hoang Thi; Thien, Dinh Duc; Quan, Nguyen Hoang; Biello, Katie B; Nunn, Amy; Chan, Philip A; Mayer, Kenneth H; Mimiaga, Matthew J; Colby, Donn
Background: The HIV/AIDS epidemic in Vietnam is concentrated in subgroups of the population, including men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) is a viable strategy for HIV prevention, but knowledge about and preferences for PrEP delivery among Vietnamese MSM are not well understood. Methods: In 2015, an online survey was conducted with recruitment via social networking websites for MSM and peer recruitment. A description of daily oral, long-acting injectable, and rectal microbicide formulations of PrEP was provided to participants. Participants were asked about their prior awareness of and interest in PrEP, and ranked their most preferred PrEP modality. Multivariable logistic regression models were used to assess factors associated with having heard of PrEP and preference for each PrEP modality. Results: Of 548 participants who answered demographic and PrEP-related questions, 26.8% had previously heard of PrEP and most (65.7%) endorsed rectal microbicides as their most preferred PrEP delivery modality. Commonly-cited perceived barriers to uptake of PrEP included concern about side-effects, perception about being HIV positive, and family or friends finding out about their sexual behaviour. In multivariable models, older participants less often endorsed rectal microbicides (adjusted odds ratio (AOR) 0.95 per year, 95% confidence interval (CI) 0.91-0.99) and more often endorsed long-acting injectables (AOR 1.08 per year, 95% CI 1.03 to 1.14) as their preferred PrEP modality. Participants who were willing to pay more for PrEP less often endorsed rectal microbicides (AOR 0.81, 95% CI 0.72-0.92) and more often endorsed long-acting injectables (AOR 1.17, 95% CI 1.01-1.35) and daily oral pills (AOR 1.16, 95% CI 1.00-1.35) as their preferred form of PrEP. Conclusions: A variety of PrEP modalities were acceptable to MSM in Vietnam, but low knowledge of PrEP may be a barrier to implementation.
Luecke, Ellen H; Cheng, Helen; Woeber, Kubashni; Nakyanzi, Teopista; Mudekunye-Mahaka, Imelda C; van der Straten, Ariane
The effectiveness of HIV pre-exposure prophylaxis (PrEP) requires consistent and correct product use, thus a deeper understanding of women's stated product formulation preferences, and the correlates of those preferences, can help guide future research. VOICE-D (MTN-003D), a qualitative ancillary study conducted after the VOICE trial, retrospectively explored participants' tablet and gel use, as well as their preferences for other potential PrEP product formulations. We conducted an analysis of quantitative and qualitative data from VOICE-D participants. During in-depth interviews, women were presented with pictures and descriptions of eight potential PrEP product formulations, including the oral tablet and vaginal gel tested in VOICE, and asked to discuss which product formulations they would prefer to use and why. Seven of the original product formulations displayed were combined into preferred product formulation categories based on exploratory factor and latent class analyses. We examined demographic and behavioural correlates of these preferred product formulation categories. In-depth interviews with participants were conducted, coded, and analysed for themes related to product preference. Of the 68 female participants who completed in-depth interviews (22 South Africa, 24 Zimbabwe, 22 Uganda), median age was 28 (range 21-41), 81% were HIV negative, and 49% were married or living with a partner. Four preferred product formulation categories were identified via exploratory factor analysis: 1) oral tablets; 2) vaginal gel; 3) injectable, implant, or vaginal ring; and 4) vaginal film or suppository. A majority of women (81%) expressed a preference for product formulations included in category 3. Characteristics significantly associated with each preferred product category differed. Attributes described by participants as being important in a preferred product formulation included duration of activity, ease of use, route of administration, clinic- versus self
Cambiano, Valentina; Miners, Alec; Dunn, David; McCormack, Sheena; Ong, Koh Jun; Gill, O Noel; Nardone, Anthony; Desai, Monica; Field, Nigel; Hart, Graham; Delpech, Valerie; Cairns, Gus; Rodger, Alison; Phillips, Andrew N
In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain. In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs. Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex. This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised
Mitchell, Kate M; Prudden, Holly J; Washington, Reynold; Isac, Shajy; Rajaram, Subramanian P; Foss, Anna M; Terris-Prestholt, Fern; Boily, Marie-Claude; Vickerman, Peter
In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life-years gained) and efficiency (life-years gained/infections averted per 100 person-years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high-risk men who have sex with men, both female sex workers and high-risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. Population attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use
Pang, Joselyn; Wei, Clayton Koh Thuan; Yee, Ilias Adam; Wang, Bangyuan; Cassolato, Matteo
Objective We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia. Methods An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants’ demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP. Results Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals. Conclusions Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services. PMID:28902857
Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.
Bil, Janneke P; van der Veldt, Wendy M; Prins, Maria; Stolte, Ineke G; Davidovich, Udi
Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs
Lim, Sin How; Mburu, Gitau; Bourne, Adam; Pang, Joselyn; Wickersham, Jeffrey A; Wei, Clayton Koh Thuan; Yee, Ilias Adam; Wang, Bangyuan; Cassolato, Matteo; Azwa, Iskandar
We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia. An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP. Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals. Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.
Bourne, Adam; Cassolato, Matteo; Thuan Wei, Clayton Koh; Wang, Bangyuan; Pang, Joselyn; Lim, Sin How; Azwa, Iskandar; Yee, Ilias; Mburu, Gitau
Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake. As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis. Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to "at-risk" men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours. This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those
Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi
Abstract Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM). Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach. Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients’ medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support. To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent
Chen, Yea-Hung; Snowden, Jonathan M; McFarland, Willi; Raymond, H Fisher
The Food and Drug Administration approved pre-exposure prophylaxis (PrEP) to prevent HIV infection, and the Centers for Disease Control and Prevention has presented PrEP as a prevention option for groups at high risk such as men who have sex with men (MSM). Intervention data provide some information on how PrEP affects sexual behavior of MSM in trials, open label extensions, or clinics. However, it is unclear whether sexual risk and preventive behavioral patterns are changing in the population as a whole as PrEP becomes more widely available, whether due to PrEP use or other factors. We examined trends in PrEP use, numbers of condomless anal sex partners, consistent condom use, and seroadaptive strategies in San Francisco-a city which has actively promoted PrEP-using data from National HIV Behavioral Surveillance (NHBS). NHBS recruited 1211, 383, 373, and 268 HIV-negative MSM in 2004, 2008, 2011, and 2014, respectively. PrEP use increased from zero in 2004, 2008, and 2011 to 9.6 % in 2014. The proportion of men with no condomless anal sex partners dropped from 60.6 % in 2004, to 58.2 % in 2008, to 54.2 % in 2011, to 40.2 % in 2014. Consistent condom use decreased from 36.8 % in 2004, and 30.5 % in 2008 and 2011, to 18.3 % in 2014. PrEP's introduction and scale-up enters in a pre-existing trend of decreasing condom use and increasing sexually transmitted infections among MSM which may be accelerating in recent years. While PrEP use should be scaled up as a prevention option among those who would benefit most, we believe that public health officials need to be realistic about the possibility that condom use could very well continue to decline as PrEP use increases, and to an extent that may not be directly or indirectly offset by PrEP.
Full Text Available OBJECTIVES: We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP. METHODS: Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP. RESULTS: Only 10 participants (2.8% reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6% reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78, <1000 RMB vs. ≥ 1000 RMB, 95% confidence interval: 1.36-5.69, perceived likelihood of contracting HIV from HIV-positive partner (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12-6.19, and worrying about being discriminated against by others due to oral PrEP use (adjusted odds ratio = 9.43, No vs. Yes, 95% confidence interval: 3.78-23.50. CONCLUSIONS: Our results showed HIV-negative partners in HIV-serodiscordant heterosexual couples in China had low awareness of oral PrEP but high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be taken into consideration in future PrEP prevention strategy. In addition, efforts should be made to reduce stigma attached to oral PrEP use, which may increase its acceptability among
Full Text Available HIV prevalence among female sex workers (FSWs in India remains well above the national average. Pre-exposure prophylaxis (PrEP, a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka.From January-April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data.Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a "double safety" in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95% expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%, those who do not use condoms when clients offer more money (58%, who do not consistently use condoms with regular partners (57%, who drink alcohol regularly (49%, and who do not use condoms consistently with clients (48%.This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means
Alistar, Sabina S.; Owens, Douglas K.; Brandeau, Margaret L.
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. PMID:24489747
Girometti, Nicolò; Gutierrez, Angela; Nwokolo, Nneka; McOwan, Alan; Whitlock, Gary
HIV pre-exposure prophylaxis (PrEP) is becoming a pivotal strategy for HIV prevention. Understanding the impact of risk factors for HIV transmission to identify those at highest risk would favour the implementation of PrEP, currently limited by costs. In this service evaluation, we estimated the incidence of bacterial STIs in men who have sex with men (MSM) diagnosed with early syphilis attending a London sexual health clinic according to their HIV status. In addition, we estimated the incidence of HIV infection in HIV-negative MSM, following a diagnosis of early syphilis. We undertook a retrospective case note review of all MSM patients diagnosed with early syphilis between January and June 2014. A number of sexual health screens and diagnoses of chlamydia, gonorrhoea and HIV were prospectively analysed following the syphilis diagnosis. 206 MSM were diagnosed with early syphilis. 110 (53%) were HIV-negative at baseline, 96 (47%) were HIV-positive. Only age (37 vs 32 years, p=0.0005) was significantly different according to HIV status of MSM at baseline. In HIV-negative versus HIV-positive MSM, incidence of rectal chlamydia infection at follow-up was 27 cases vs 50/100 person-years of follow-up (PYFU) (p=0.0039), 33 vs 66/100 PYFU (p=0.0044) for rectal gonorrhoea and 10 vs 26/100 PYFU (p=0.0044) for syphilis reinfection, respectively. Total follow-up for 110 HIV-negative MSM was 144 person-years. HIV incidence was 8.3/100 PYFU (CI 4.2 to 14). A diagnosis of early syphilis carries a high risk of consequent HIV seroconversion and should warrant prioritised access to prevention measures such as PrEP and regular STI screening to prevent HIV transmission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Full Text Available Tenofovir-emtricitabine (TDF-FTC pre-exposure prophylaxis (PrEP has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA scans at the hip, spine, and forearm.A total of 220 participants (108 TDF-FTC, 112 placebo had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8% participants had low baseline BMD (z-score of 3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0% TDF-FTC vs. 26/79 (32.9% placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01, spine -1.62% (p = 0.0002, hip -1.51% (p = 0.003].Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8% of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.ClinicalTrials.gov NCT00448669.
Holloway, Ian W; Tan, Diane; Gildner, Jennifer L; Beougher, Sean C; Pulsipher, Craig; Montoya, Jorge A; Plant, Aaron; Leibowitz, Arleen
While correlates of pre-exposure prophylaxis (PrEP) uptake have been explored among older men who have sex with men (MSM), less is known about the facilitators and barriers that encourage uptake among younger MSM (YMSM). This study explores the association between willingness to take PrEP and demographic characteristics, sexual risk, and substance use, and attitudinal factors among YMSM in California who use geosocial networking applications (GSN apps). Based on survey data from YMSM recruited through GSN apps (n = 687), PrEP willingness was positively associated with Hispanic ethnicity [adjusted odds ratio (aOR): 1.73; confidence interval (CI): 1.01-2.98; p = 0.046], concerns about drug effects (aOR: 0.46; CI: 0.33-0.65; p < 0.001), medical mistrust (aOR: 0.71; CI: 0.53-0.96; p < 0.001), and concerns about adherence (aOR: 0.65; CI: 0.49-0.89; p = 0.005). PrEP willingness was positively associated with medium (aOR: 1.87; CI: 1.14-3.07; p = 0.014) and high concern (aOR: 1.84; CI: 1.13-3.01; p < 0.001) about contracting HIV and perceived benefits of taking PrEP (aOR: 2.59; CI: 1.78-3.78; p < 0.001). In addition to emphasizing the benefits of using PrEP, campaigns that address concerns regarding adherence and side effects may increase interest in and demand for PrEP among YMSM. More opportunities are needed to educate YMSM about PrEP, including addressing their concerns about this new prevention strategy. Providers should speak openly and honestly to YMSM considering PrEP about what to do if side effects occur and how to handle missed doses. Outreach using GSN apps for PrEP education and screening may be an effective way to reach YMSM.
Gabriela B Gomez
Full Text Available 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.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.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
Punyacharoensin, Narat; Edmunds, William John; De Angelis, Daniela; Delpech, Valerie; Hart, Graham; Elford, Jonathan; Brown, Alison; Gill, O Noel; White, Richard Guy
HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection. We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15-64 years) in the UK during 2014-20, including increasing rates of HIV testing, test-and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation. We predicted a baseline of 16 955 new infections (IQR 13 156-21 669) in MSM in the UK during 2014-20. At a coverage of ≤50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61·8%, IQR 47·2-81·8, of total incidence) was greater than the sum of effects of the two interventions individually (32·6%, 23·7-46·0, and 23·9%, 16·5-33·3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587-9813) UK MSM from HIV infection (43·6%, IQR 32·9-57·9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely. PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade. Health Protection Agency (now Public Health England). Copyright © 2016 Elsevier Ltd. All rights reserved.
Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I
The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.
McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N
Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23
Nic Lochlainn, Laura; O'Donnell, Kate; Hurley, Caroline; Lyons, Fiona; Igoe, Derval
In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition. We estimated MSM numbers likely to present for PrEP by applying French PrEP criteria to Irish MSM behavioural survey data. We adjusted for survey bias, calculated proportions accessing testing services and those likely to take PrEP. We estimated 1-3% of MSM in Ireland were likely to present for PrEP.
Underhill, Kristen; Morrow, Kathleen M.; Operario, Don; Mayer, Kenneth H.
The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while o...
Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa
Background:\\ud Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design.\\ud Methods:\\ud Quantitative surveys of n = 690 MSM recruited online via social a...
Kenneth K Mugwanya
Full Text Available As pre-exposure prophylaxis (PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748. The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1-2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS assays. Of the 50 mother-infant pairs enrolled, 48% were ≤12 wk and 52% were 13-24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22-28. During study follow-up, the median (IQR daily reported frequency of infant breastfeeding was 15 times (12 to 18 overall, 16 (14 to 19 for the ≤12 weeks, and 14 (12 to 17 for the 13-24 wk infant age groups. Overall, median (IQR time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7 for tenofovir and 212.5 ng/mL (140.0 to 405.0 for
Draper, Bridget L; Fowkes, Freya J I; Oo, Zaw Min; Thein, Zaw Win; Aung, Poe Poe; Veronese, Vanessa; Ryan, Claire; Thant, Myo; Hughes, Chad; Stoové, Mark
HIV pre-exposure prophylaxis (PrEP) has emerged as a key component of contemporary HIV combination prevention strategies. To explore the local suitability of PrEP, country-specific acceptability studies are needed to inform potential PrEP implementation. In the context of Myanmar, in addition to resource constraints, HIV service access by gay men, other men who have sex with men, and transgender women (GMT) continues to be constrained by legislative and community stigma and marginalization. We aimed to determine PrEP acceptability among GMT in Myanmar and explore the factors associated with willingness to use PrEP. GMT were recruited in Yangon and Mandalay through local HIV prevention outreach programmes in November and December 2014. Quantitative surveys were administered by trained peer educators and collected data on demographics, sexual risk, testing history and PrEP acceptability. A modified six-item PrEP acceptability scale classified self-reported HIV undiagnosed GMT as willing to use PrEP. Multivariable logistic regression identified factors associated with willingness to use PrEP. Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%). PrEP acceptability was high, with 270 (62%) GMT classified as willing to use PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05-3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82; 95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94; 95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The association between never or only occasionally using condoms with casual partners and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00-4.10). GMT who reported concern about side effects and long-term use of PrEP were less
Full Text Available Operational research is required to design delivery of pre-exposure prophylaxis (PrEP and early antiretroviral treatment (ART. This paper presents the primary analysis of programmatic data, as well as demographic, behavioural, and clinical data, from the TAPS Demonstration Project, which offered both interventions to female sex workers (FSWs at 2 urban clinic sites in South Africa.The TAPS study was conducted between 30 March 2015 and 30 June 2017, with the enrolment period ending on 31 July 2016. TAPS was a prospective observational cohort study with 2 groups receiving interventions delivered in existing service settings: (1 PrEP as part of combination prevention for HIV-negative FSWs and (2 early ART for HIV-positive FSWs. The main outcome was programme retention at 12 months of follow-up. Of the 947 FSWs initially seen in clinic, 692 were HIV tested. HIV prevalence was 49%. Among those returning to clinic after HIV testing and clinical screening, 93% of the women who were HIV-negative were confirmed as clinically eligible for PrEP (n = 224/241, and 41% (n = 110/270 of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment. Of the remaining women who were HIV-positive, 93% were eligible for early ART (n = 148/160. From those eligible, 98% (n = 219/224 and 94% (n = 139/148 took up PrEP and early ART, respectively. At baseline, a substantial fraction of women had a steady partner, worked in brothels, and were born in Zimbabwe. Of those enrolled, 22% on PrEP (n = 49/219 and 60% on early ART (n = 83/139 were seen at 12 months; we observed high rates of loss to follow-up: 71% (n = 156/219 and 30% (n = 42/139 in the PrEP and early ART groups, respectively. Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days, with high levels of consistent condom use with clients and low use with steady partners in both study groups
Southern African HIV Clinicians Society Consensus Committee
Full Text Available Background. The use of oral antiretrovirals to prevent HIV infection among HIV-negative men who have sex with men (MSM has been shown to be safe and efficacious. A large, randomised, placebo-controlled trial showed a 44% reduction in the incidence of HIV infection among MSM receiving a daily oral fixed-dose combination of tenofovir disoproxil fumarate and emtricitabine (Truvada in combination with an HIV prevention package. Improved protection was seen with higher levels of adherence. Aim. The purpose of this guideline is to: (i explain what pre-exposure prophylaxis (PrEP is; (ii outline current indications for its use; (iii outline steps for appropriate client selection; and (iv provide guidance for monitoring and maintaining clients on PrEP. Method. PrEP is indicated for HIV-negative MSM who are assessed to be at high risk for HIV acquisition and who are willing and motivated to use PrEP as part of a package of HIV prevention services (including condoms, lubrication, sexually transmitted infection (STI management and risk reduction counselling. Recommendations. HIV testing, estimation of creatinine clearance and STI and hepatitis B screening are recommended as baseline investigations. Daily oral Truvada, along with adherence support, can then be prescribed for eligible MSM. PrEP should not be given to MSM with abnormal renal function, nor to clients who are unmotivated to use PrEP as part of an HIV prevention package; nor should it be commenced during an acute viral illness. Three-monthly follow-up visits to assess tolerance, renal function, adherence and ongoing eligibility is recommended. Six-monthly STI screens and annual creatinine levels to estimate creatinine clearance are recommended. Hepatitis B vaccination should be provided to susceptible clients. Gastro-intestinal symptoms and weight loss are common side-effects, mostly experienced for the first 4 - 8 weeks after initiating PrEP. There is a risk of the development of antiretroviral
Xie, P Y; Wang, X; Liu, P L; Tan, X D; Zhou, W
Objective: To understand willingness and influencing factors of using pre-exposure prophylaxis (Pr-EP) among men who have sex with men (MSM). Methods: Snow ball sampling was employed to recruit MSM in the social spaces (like bars and bathrooms) with focused activities by MSM and internet (QQ and Wechat) in Wuhan between August and November, 2015. 304 MSM were considered eligible when they were self-identified MSM and has had sex with men in the previous 12 months, over the age of 18 and have full civil liability. On-site and online questionnaire surveys were conducted by self-designed questionnaires to collect information including demographic characteristics, sexual risks and practices, awareness of PrEP, and willingness to use PrEP. A total of 301 qualified questionnaires were obtained. Multivariate logistic regression models were constructed to identify factors associated with willingness to use Pr-EP. Results: The mean age of surveyed MSM were (27.51±8.31) years, between18-61. 149 on-site survey, online were152; 131 MSM have regular homosexual partners, 170 MSM have not regular homosexual partners. Only 17.28% (52/301) had heard of Pr-EP before this survey, 18.32% (24/130) had heard of Pr-EP among those who had regular homosexual partners and those who had not accounted for 16.47% (28/170). 74.42% (224/301) had willingness to use Pr-EP after they knew Pr-EP was safe and effective through the survey. The proportion among those who had regular homosexual partners was 74.05%(74), and the proportion among those who had not was 74.71% (127); Among those who had regular homosexual partners, results suggested that those who were married/cohabiting were more likely to report a willingness to use PrEP compared to unmarried/divorced or widowed ( OR= 5.60), compared with homosexual, heterosexuality was associated with decreased odds of willingness to use Pr-EP ( OR= 0.22), compared with HIV status of sexual partner was negative or uncertain, positive infection status was
Hugo, J M; Stall, R D; Rebe, K; Egan, J E; De Swardt, G; Struthers, H; McIntyre, J A
Men who have Sex with Men (MSM) have been affected disproportionately by the global HIV pandemic. Rates of consistent condom-use are low and there is a need for further biomedical prevention interventions to prevent new HIV infections. Post exposure prophylaxis (PEP) can reduce the risk of HIV, but uptake among MSM is low. Pre-exposure prophylaxis (PrEP), an innovative anti-retroviral-based HIV prevention tool might be an appropriate intervention for MSM who have recently accessed PEP that involves HIV negative individuals taking daily tenofovir+emtricitabine for HIV prevention. 44 MSM, attending a primary health-care level MSM-focused sexual health clinic in Cape Town, South Africa, who had initiated PEP were enrolled in this study. Participants were followed up after 2, 4 and 12 weeks. Self-administered electronic surveys were completed at the initial, 4 and 12 week visit. Barriers and facilitators to accessing PEP and remaining adherent were examined, as was knowledge about PrEP. Thirty-two participants (80 %) were <40 years of age (range 20-65 years). 35 % of the participants reported their reason for requiring PEP as condomless receptive anal intercourse. A further 20 % required PEP following condomless penetrative anal intercourse; 27.5 % required PEP due to a broken condom during receptive anal sex and 2 participants during insertive anal sex. Three participants did not complete 28 days of PEP or were lost to follow up. Over half (58.5 %) of the participants reported being completely adherent to their regime; under a third (31.7 %) reported missing one PEP dose; and 9.8 % reported missing more than one dose. 36/40 (90 %) had heard of PrEP and 30/40 (75 %) indicated that they would use PrEP if it were accessible to them. That we enrolled 44 MSM who accessed PEP from a Department of Health affiliated clinic over 12 months, speaks to the low uptake by MSM of PEP services in South Africa. Adherence was high and demonstrates that adherence
Walters, Suzan M; Rivera, Alexis V; Starbuck, Lila; Reilly, Kathleen H; Boldon, Nyasha; Anderson, Bridget J; Braunstein, Sarah
Pre-exposure prophylaxis (PrEP) to reduce the risk of HIV was approved in 2012 and post-exposure prophylaxis (PEP) in 2005. We report the differences in awareness of PrEP/PEP and factors associated with awareness by examining 3 risk groups (men who have sex with men (MSM), people who inject drugs, and high-risk heterosexuals). National HIV Behavioral Surveillance system data collected in New York City (NYC) and Long Island, NY in 2011-2013 were used. Logistic regressions by region were developed to estimate adjusted associations [Adjusted Odds Ratios (AOR)] and determine differences in awareness of PrEP/PEP. Awareness of PrEP/PEP was low for all groups. In multivariate analysis controlling for sociodemographic factors, noninjection drug use, HIV status, and exposure to HIV prevention, males who inject drugs in NYC had significantly decreased odds of PrEP/PEP awareness [AOR: 0.45; confidence interval (CI): 0.25 to 0.81] compared with MSM. MSM aged 18-29 years had increased awareness of PrEP (AOR: 2.94; 95% CI 1.11 to 7.80). On Long Island, females who inject drugs (AOR: 0.18; 95% CI: 0.05 to 0.62), males who inject drugs (AOR: 0.14; 95% CI: 0.05 to 0.39), female heterosexuals (AOR: 0.25; 95% CI: 0.11 to 0.59), and male heterosexuals (AOR: 0.32; 95% CI: 0.14 to 0.73) had significantly decreased odds of PrEP/PEP awareness. Black MSM had increased awareness of PrEP (AOR: 4.08 CI:1.21 to 13.73). Large proportions of groups at-risk for HIV were unaware of PrEP/PEP. When comparing risk groups to MSM, we found MSM to have greater awareness in both regions. On Long Island, people who inject drugs and heterosexuals were far less likely to have PrEP/PEP awareness than in NYC. On Long Island, Black MSM had increased PrEP awareness and in NYC MSM aged 18-29 had increased PrEP awareness. These findings suggest that awareness may be spreading through networks and highlight the importance of targeted educational and prevention efforts by group and region.
Thomson, Kerry A; Haberer, Jessica E; Marzinke, Mark A; Mujugira, Andrew; Hendrix, Craig W; Celum, Connie; Ndase, Patrick; Ronald, Allan; Bangsberg, David R; Baeten, Jared M
Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%-1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3-292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.
Seidman, Dominika L; Weber, Shannon; Timoney, Maria Teresa; Oza, Karishma K; Mullins, Elizabeth; Cohan, Deborah L; Wright, Rodney L
Pregnancy may increase a woman's susceptibility to HIV. Maternal HIV acquisition during pregnancy and lactation is associated with increased perinatal and lactational HIV transmission. There are no published reports of preexposure prophylaxis use after the first trimester of pregnancy or during lactation. The purpose of this study was to report the use of preexposure prophylaxis and to identify gaps in HIV prevention services for women who were at substantial risk of HIV preconception and during pregnancy and lactation at 2 United States medical centers. Chart review was performed on women who were identified as "at significant risk" for HIV acquisition preconception (women desiring pregnancy) and during pregnancy and lactation at 2 medical centers in San Francisco and New York from 2010-2015. Women were referred to specialty clinics for women who were living with or were at substantial risk of HIV. Twenty-seven women who were identified had a median age of 27 years. One-half of the women had unstable housing, 22% of the women had ongoing intimate partner violence, and 22% of the women had active substance use. Twenty-six women had a male partner living with HIV, and 1 woman had a male partner who had sex with men. Of the partners who were living with HIV, 73% (19/26) were receiving antiretroviral therapy, and 42% (11/26) had documented viral suppression. Thirty-nine percent (10/26) of partners had known detectable virus, and 19% (5/26) had unknown viral loads. Women were identified by clinicians, health educators, and health departments. Approximately one-third of the women were identified preconception (8/27); the majority of the women were identified during pregnancy (18/27) with a median gestational age of 20 weeks (interquartile range, 11-23), and 1 woman was identified in the postpartum period. None of the pregnant referrals had received safer conception counseling to reduce HIV transmission. Twenty-six percent of all women (7/27) were eligible for
Guise, Andy; Albers, Eliot Ross; Strathdee, Steffanie A
Pre-exposure prophylaxis for HIV, or 'PrEP', is the use of antiretroviral medicines by people who are HIV-negative to protect themselves against acquiring HIV. PrEP has shown efficacy for preventing HIV acquisition. Despite the potential, many concerns have been voiced by people who inject drugs (PWID) and their organizations. There is a need to engage with these views and ensure their integration in to policy and strategy. This paper presents PWID views on PrEP to foster the uptake of these opinions into scientific and policy debate around PrEP METHODS: Critical analysis of a report of a community consultation led by the International Network of People who Use Drugs (INPUD). The INPUD report highlights enthusiasm from PWID for PrEP, but also three main concerns: the feasibility and ethics of PrEP, its potential use as a substitute for other harm reduction strategies and how a focus on PrEP heralds a re-medicalization of HIV. Each concern relates to evidenced gaps in essential services or opposition to harm reduction and PWID human rights. People who use drugs have fundamental concerns about the potential impacts of pre-exposure prophylaxis for HIV which reflect a 'fault line' in HIV prevention: a predominance of biomedical approaches over community perspectives. Greater community engagement in HIV prevention strategy is needed, or we risk continuing to ignore the need for action on the underlying structural drivers and social context of the HIV epidemic. © 2016 Society for the Study of Addiction.
Mimiaga, Matthew J; Closson, Elizabeth F; Kothary, Vishesh; Mitty, Jennifer A
Men who have sex with men (MSM) remain at great risk of HIV in the United States, representing 65 % of incident HIV infections. One factor contributing to the high rate of HIV infection among MSM is use of "recreational" drugs that are highly associated with unprotected anal sex. Pre-exposure chemoprophylaxis (PrEP) is a novel biomedical HIV prevention strategy that has the potential to reduce HIV transmission in MSM. Main and casual sex partners play a role in HIV prevention efforts for MSM. The study aimed to qualitatively explore the perceived influences of sexual relationships on promoting and inhibiting PrEP use among high-risk MSM who report regular drug use. Semi-structured qualitative interviews were conducted with 40 participants recruited in Boston, Massachusetts. Data were analyzed using descriptive qualitative analysis. Casual partners presented a distinct set of concerns from primary partnerships. MSM generally viewed main partners as a potential source of support for taking PrEP. Given their informal and often temporary nature, PrEP disclosure to casual partners was considered unnecessary. HIV-related stigma and substance use were also perceived as barriers to discussing PrEP use with casual partners. MSM articulated a high degree of personal agency regarding their ability to take PrEP. Findings suggest that behavioral interventions to improve PrEP utilization and adherence for high-risk MSM should be tailored to sex partner type and the parameters established between sex partners. Approaches to PrEP disclosure and partner engagement should be informed by the relative benefits and limitations characterized by these different types of relationships.
Duthie, Malcolm S; Pena, Maria T; Ebenezer, Gigi J; Gillis, Thomas P; Sharma, Rahul; Cunningham, Kelly; Polydefkis, Michael; Maeda, Yumi; Makino, Masahiko; Truman, Richard W; Reed, Steven G
Sustained elimination of leprosy as a global health concern likely requires a vaccine. The current standard, BCG, confers only partial protection and precipitates paucibacillary (PB) disease in some instances. When injected into mice with the T helper 1 (Th1)-biasing adjuvant formulation Glucopyranosyl Lipid Adjuvant in stable emulsion (GLA-SE), a cocktail of three prioritized antigens (ML2055, ML2380 and ML2028) reduced M. leprae infection levels. Recognition and protective efficacy of a single chimeric fusion protein incorporating these antigens, LEP-F1, was confirmed in similar experiments. The impact of post-exposure immunization was then assessed in nine-banded armadillos that demonstrate a functional recapitulation of leprosy. Armadillos were infected with M. leprae 1 month before the initiation of post-exposure prophylaxis. While BCG precipitated motor nerve conduction abnormalities more rapidly and severely than observed for control infected armadillos, motor nerve injury in armadillos treated three times, at monthly intervals with LepVax was appreciably delayed. Biopsy of cutaneous nerves indicated that epidermal nerve fiber density was not significantly altered in M. leprae -infected animals although Remak Schwann cells of the cutaneous nerves in the distal leg were denser in the infected armadillos. Importantly, LepVax immunization did not exacerbate cutaneous nerve involvement due to M. leprae infection, indicating its safe use. There was no intraneural inflammation but a reduction of intra axonal edema suggested that LepVax treatment might restore some early sensory axonal function. These data indicate that post-exposure prophylaxis with LepVax not only appears safe but, unlike BCG, alleviates and delays the neurologic disruptions caused by M. leprae infection.
Full Text Available We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM. Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it.We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes.Among 328 men (164 couples, 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse.Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.
Saberi, Parya; Gamarel, Kristi E; Neilands, Torsten B; Comfort, Megan; Sheon, Nicolas; Darbes, Lynae A; Johnson, Mallory O
We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple. Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it. We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes. Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse. Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.
Correlates of Awareness of and Willingness to Use Pre-exposure Prophylaxis (PrEP) in Gay, Bisexual, and Other Men Who Have Sex with Men Who Use Geosocial-Networking Smartphone Applications in New York City.
Goedel, William C; Halkitis, Perry N; Greene, Richard E; Duncan, Dustin T
Geosocial-networking smartphone applications are commonly used by gay, bisexual, and other men who have sex with men (MSM) to meet sexual partners. The purpose of the current study was to evaluate awareness of and willingness to use pre-exposure prophylaxis (PrEP) among MSM who use geosocial-networking smartphone applications residing in New York City. Recruitment utilizing broadcast advertisements on a popular smartphone application for MSM yielded a sample of 152 HIV-uninfected MSM. Multivariable models were used to assess demographic and behavioral correlates of awareness of and willingness to use PrEP. Most participants (85.5 %) had heard about PrEP but few (9.2 %) reported current use. Unwillingness to use PrEP was associated with concerns about side effects (PR = 0.303; 95 % CI 0.130, 0.708; p = 0.006). Given that more than half (57.6 %) of participants were willing to use PrEP, future research is needed to elucidate both individual and structural barriers to PrEP use among MSM.
The intention to use HIV-pre-exposure prophylaxis (PrEP) among men who have sex with men in Switzerland: testing an extended explanatory model drawing on the unified theory of acceptance and use of technology (UTAUT).
Nideröst, Sibylle; Gredig, Daniel; Hassler, Benedikt; Uggowitzer, Franziska; Weber, Patrick
The aim of this study was to determine the intention to use pre-exposure prophylaxis (PrEP) when available and to identify predictors of the intention to use PrEP among men who have sex with men (MSM) living in Switzerland. The theoretical model drew on the Unified Theory of Acceptance and Use of Technology and considered additional variables related specifically to PrEP, HIV protection and the resources of MSM. For data collection, we used an anonymous, standardized self-administered online questionnaire. In 2015, we gathered a convenience sample of 556 HIV-negative MSM living in Switzerland. We analyzed the data using descriptive and bivariate statistics and used structural equation modeling to test the hypothesized model. Predictors of respondents' moderate intention to use PrEP were performance expectancy, effort expectancy, perceived social influence, concerns about using PrEP, attitudes toward condom use, negative experiences of condom use and age. These variables were predicted by HIV protection-related aspects and resources. The findings provide insights into the complex dynamic underlying the intention to use PrEP.
Greene, George J; Swann, Greg; Fought, Angela J; Carballo-Diéguez, Alex; Hope, Thomas J; Kiser, Patrick F; Mustanski, Brian; D'Aquila, Richard T
HIV prevention method preferences were evaluated among 512 U.S. men who have sex with men (MSM; median age: 22 years). Approximately 90 % consistently preferred one option across pairwise comparisons of condoms, daily oral pre-exposure prophylaxis (PrEP), and long-acting PrEP delivered via either an injectable or one of two types of PrEP implants differing in visibility. Condoms were most frequently preferred (33.8 %), followed by non-visible implants (21.5 %), and oral PrEP (17.0 %); HIV risk was reported by more choosing implants. In a follow-up question comparing the four PrEP options only, daily oral pills and non-visible implants were most frequently preferred (35.5 and 34.3 %, respectively), followed by injections (25.2 %) and visible implants (4.3 %). An inductive, open-coding approach determined that convenience, duration of protection, and privacy were the most commonly cited reasons for a PrEP method choice, and associated with self-report of HIV risk. Tailoring PrEP product development to privacy and other concerns important to those at highest HIV risk may improve HIV prevention.
Garcia, Jonathan; Colson, Paul W; Parker, Caroline; Hirsch, Jennifer S
Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial drawing on findings from the community-based ethnography. This article describes how ethnographic findings informed the RCT and identifies distilled themes and findings that could be included as part of an RCT. The enhanced intervention includes in-person support groups, online support groups, peer navigation, and text message reminders. By describing key process-related facilitators and barriers to conducting meaningful mixed methods research, we provide important insights for the practice of designing clinical trials for 'real-world' community settings. Copyright © 2015 Elsevier Inc. All rights reserved.
Underhill, Kristen; Morrow, Kathleen M; Operario, Don; Mayer, Kenneth H
The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while others perceived approval as irrelevant or less significant than other sources of information. Our results suggest that FDA approval sends a signal that directly shapes PrEP acceptability among some MSM, while indirect influences of approval may affect uptake by others. Efforts to educate MSM about PrEP can increase acceptability by incorporating information about FDA approval, and outreach strategies should consider how this information may factor into personal decisions about PrEP use.
Gilmore, Hailey J; Liu, Albert; Koester, Kimberly Ann; Amico, K Rivet; McMahan, Vanessa; Goicochea, Pedro; Vargas, Lorena; Lubensky, David; Buchbinder, Susan; Grant, Robert
In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV acquisition among men who have sex with men. Adherence to study product was critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates highest in the United States. We conducted a qualitative study to gain insights into the experiences of iPrEx participants in San Francisco (SF) where there was high confirmed adherence, to understand individual and contextual factors influencing study product use in this community. In 2009 and 2011, we conducted focus groups and in-depth interviews in 36 and 16 SF iPrEx participants, respectively. Qualitative analyses indicate that participants joined the study out of altruism. They had a clear understanding of study product use, and pill taking was facilitated by establishing or building on an existing routine. Participants valued healthcare provided by the study and relationships with staff, whom they perceived as nonjudgmental, and found client-centered counseling to be an important part of the PrEP package. This facilitated pill taking and accurate reporting of missed doses. Adherence barriers included changes in routine, side effects/intercurrent illnesses, and stress. Future PrEP adherence interventions should leverage existing routines and establish client-centered relationships/ environments to support pill taking and promote accurate reporting.
Van der Elst, Elisabeth Maria; Mbogua, Judie; Operario, Don; Mutua, Gaudensia; Kuo, Caroline; Mugo, Peter; Kanungi, Jennifer; Singh, Sagri; Haberer, Jessica; Priddy, Frances; Sanders, Eduard Joachim
This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.
Alignment of adherence and risk for HIV acquisition in a demonstration project of pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention-effective adherence.
Haberer, Jessica E; Kidoguchi, Lara; Heffron, Renee; Mugo, Nelly; Bukusi, Elizabeth; Katabira, Elly; Asiimwe, Stephen; Thomas, Katherine K; Celum, Connie; Baeten, Jared M
Adherence is essential for pre-exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most efficient when its use is aligned with periods of risk - a concept termed prevention-effective adherence. The objective of this paper is to describe prevention-effective adherence and predictors of adherence within an open-label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project). We offered PrEP to HIV-uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as "PrEP as a bridge to ART"). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with 25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months of follow-up, ART use >6 months by the partner living with HIV and problem alcohol use. Over three-quarters of participant-visits by HIV-uninfected partners in serodiscordant couples achieved prevention-effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.
Full Text Available 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.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.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.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.
Eaton, Lisa A; Matthews, Derrick D; Driffin, Daniel D; Bukowski, Leigh; Wilson, Patrick A; Stall, Ron D
The HIV epidemic among Black men and transgender women who have sex with men (BMTW) demands an urgent public health response. HIV point prevalence among this population ranges from 25 to 43%-a rate far exceeding any other group. Pre-exposure prophylaxis (PrEP) for HIV prevention is a very promising prevention tool; however, its full potential to slow the epidemic has yet to be realized. For the current study, random time-location sampling at Black Gay Pride Events was used to collect data from N = 1274 BMTW, from five US cities, reporting HIV-negative/unknown status. In-field HIV testing was also provided to participants. Participants were assessed on awareness and use of PrEP, health care factors, HIV testing history, psychosocial variables, and sex behaviors. About one third of participants were aware of PrEP (39%), and a small percentage of participants were users of PrEP (4.6%). In multivariable analyses, being in a relationship, testing for HIV in the past 6 months, and others being aware of one's sexuality were positively associated with PrEP awareness. Higher levels of internalized homophobia and greater numbers of female sex partners were positively associated with PrEP use, while education and condom use were negatively associated. Based on study findings, messaging and uptake of PrEP needs greater expansion and requires novel approaches for scale-up. Improving linkage to HIV testing services is likely critical for engaging BMTW with PrEP. The potential for PrEP to slow the HIV epidemic is high; however, we must strengthen efforts to ensure universal availability and uptake.
Shrestha, Roman; Altice, Frederick L; Huedo-Medina, Tania B; Karki, Pramila; Copenhaver, Michael
Evidence from recent pre-exposure prophylaxis (PrEP) trials has demonstrated its safety and efficacy in significantly reducing the risk of HIV acquisition for those who are at considerable risk of acquiring HIV infection. With a rapid increase in the amount of research on the efficacy of PrEP for HIV prevention, complementary research on the willingness to use PrEP has grown, especially among MSM, but limited research has been focused among people who use drugs (PWUD). As part of the formative process, we utilized the information-motivation-behavioral skills (IMB) model of health behavior change to characterize and guide intervention development for promoting willingness to use PrEP among high-risk PWUD. The analysis included 400 HIV-negative high-risk PWUD enrolled in a community-based methadone maintenance treatment who reported drug- and/or sex-related HIV risk behaviors in the past 6-months. Analyses revealed support for the IMB model as PrEP-related behavioral skills were found to mediate the influence of PrEP-related information and motivation on willingness to use PrEP. The results provide evidence as to the utility of the IMB model to increase willingness to use PrEP among high-risk PWUD. It therefore makes an important contribution to our understanding of the applicability of theoretically-grounded models of willingness to use PrEP among high-risk PWUD, who are one of the key risk populations who could benefit from the use of PrEP.
Marra, Elske; Hankins, Catherine A
Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the Netherlands explored perceptions of MSM and their willingness to use oral PrEP and rectal microbicides (RM) if made available. Recruited through social media (Facebook and Twitter), 108 MSM completed online questionnaires. Seven of them consented to discuss the survey results in semi-structured interviews. Survey participants preferred a RM that could be applied before and after anal intercourse (60.8%) to daily oral PrEP (20.3%). This preference was based on anticipated user friendliness, hypothetically fewer expected adverse events, and perceptions that RM would be less likely to be confused with ARVs for treatment. Those who preferred oral PrEP had stronger beliefs in the effectiveness of pills, perceived its use as easy, and viewed not requiring sexual partner awareness as advantages. No predictive factors were found for the choice of one prevention method over the other. Although Dutch MSM perceive both oral and topical PrEP positively, many barriers exist to the introduction of these products in the Netherlands. These include lack of regulatory approval of oral PrEP, no proven efficacy as yet for RM, and strong HIV stigma within the MSM population. In-depth qualitative research is needed to further explore the perceptions of MSM to inform implementation of programmes should these HIV prevention methods become available.
Traeger, Michael W; Schroeder, Sophia E; Wright, Edwina J; Hellard, Margaret E; Cornelisse, Vincent J; Doyle, Joseph S; Stoové, Mark A
HIV pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM. We conducted a systematic review of open-label trials and observational studies published to August 2017 reporting sexual risk outcomes (STI diagnoses, condom use, number of sexual partners) in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis and a qualitative review and risk of bias assessment were performed. Sixteen observational studies and one open-label trial met selection criteria. Eight studies with 4388 participants reported STI prevalence and 13 studies with 5008 participants reported change in condom use. PrEP use was associated with a significant increase in rectal chlamydia (odds ratio [OR]=1.59; 95%CI 1.19-2.13; p=0.002; heterogeneity I 2=23%) and an increase in any STI diagnosis (OR=1.24; 95%CI 0.99-1.54; p=0.059; I 2=50%). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users. Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies.
Underhill, Kristen; Morrow, Kathleen M; Colleran, Christopher M; Holcomb, Richard; Operario, Don; Calabrese, Sarah K; Galárraga, Omar; Mayer, Kenneth H
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. 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. 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. 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.
... Español El VIH es una amenaza de salud grave para las comunidades latinas, quienes se encuentran en gran desventaja respecto de la incidencia de esta enfermedad en los Estados Unidos. Según los CDC, en ...
... Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: The Basics Just ... to HIV frequently. Another HIV prevention method, called pre-exposure prophylaxis or PrEP, is when people at high risk ...
Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.
Freddie M Kibengo
Full Text Available BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS and self-report. Sexual activity data were collected via daily short text message (SMS and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100 for daily PrEP regimen, 91% (IQR: 73-97 for fixed intermittent dosing and 45% (IQR: 20-63 for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be
Yi, Siyan; Tuot, Sovannary; Mwai, Grace W; Ngin, Chanrith; Chhim, Kolab; Pal, Khoundyla; Igbinedion, Ewemade; Holland, Paula; Choub, Sok Chamreun; Mburu, Gitau
Abstract Introduction: To facilitate provision of pre-exposure prophylaxis (PrEP) in low- and middle-income countries (LMIC), a better understanding of potential demand and user preferences is required. This review assessed awareness and willingness to use oral PrEP among men who have sex with men (MSM) in LMIC. Methods: Electronic literature search of Cochrane library, Embase, PubMed, PsychINFO, CINHAL, Web of Science, and Google Scholar was conducted between July and September 2016. Reference lists of relevant studies were searched, and three authors contacted for additional data. Non-peer reviewed publications were excluded. Studies were screened for inclusion, and relevant data abstracted, assessed for bias, and synthesized. Results: In total, 2186 records were identified, of which 23 studies involving 14,040 MSM from LMIC were included. The proportion of MSM who were aware of PrEP was low at 29.7% (95% CI: 16.9–44.3). However, the proportion willing to use PrEP was higher, at 64.4% (95% CI: 53.3–74.8). Proportions of MSM aware of PrEP was <50% in 11 studies and 50–70% in 3 studies, while willingness to use PrEP was <50% in 6 studies, 50–70% in 9 studies, and over 80% in 5 studies. Several factors affected willingness to use PrEP. At the individual domain, poor knowledge of PrEP, doubts about its effectiveness, fear of side effects, low perception of HIV risk, and the need to adhere or take medicines frequently reduced willingness to use PrEP, while PrEP education and motivation to maintain good health were facilitators of potential use. Demographic factors (education, age, and migration) influenced both awareness and willingness to use PrEP, but their effects were not consistent across studies. At the social domain, anticipated stigma from peers, partners, and family members related to sexual orientation, PrEP, or HIV status were barriers to potential use of PrEP, while partner, peer, and family support were facilitators of potential use. At the
Functional Knowledge of Pre-Exposure Prophylaxis for HIV Prevention Among Participants in a Web-Based Survey of Sexually Active Gay, Bisexual, and Other Men Who Have Sex With Men: Cross-Sectional Study
Background Awareness of pre-exposure prophylaxis (PrEP) for HIV prevention is increasing, but little is known about the functional knowledge of PrEP and its impact on willingness to use PrEP. Objective The objective of this study was to assess the functional knowledge of PrEP among a sample of gay, bisexual, and other men who have sex with men (MSM) participating in a Web-based survey of sexually active MSM. Methods Men at least 18 years old, residing in the United States, and reporting sex with a man in the previous 6 months were recruited through social networking websites. PrEP functional knowledge included the following 4 questions (1) efficacy of consistent PrEP use, (2) inconsistent PrEP use and effectiveness, (3) PrEP and condom use, and (4) effectiveness at reducing sexually transmitted infections (STIs). Ordinal logistic regression was used to identify respondent characteristics associated with PrEP functional knowledge. In a subsample of participants responding to HIV prevention questions, we compared willingness to use PrEP by response to PrEP functional knowledge using logistic regression analysis adjusted for age, race and ethnicity, and education level. Results Among 573 respondents, PrEP knowledge was high regarding adherence (488/573, 85.2%), condom use (532/573, 92.8%), and STIs (480/573, 83.8%), but only 252/573 (44.0%) identified the correct efficacy. Lower functional PrEP knowledge was associated with minority race/ethnicity (P=.005), lower education (P=.01), and not having an HIV test in the past year (P=.02). Higher PrEP knowledge was associated with willingness to use PrEP (P=.009). Younger age was not associated with higher PrEP functional knowledge or willingness to use PrEP. Conclusions PrEP knowledge was generally high in our study, including condom use and consistent use but may be lacking in higher risk MSM. The majority of respondents did not correctly identify PrEP efficacy with consistent use, which could impact motivation to seek
Rendina, H Jonathon; Whitfield, Thomas H F; Grov, Christian; Starks, Tyrel J; Parsons, Jeffrey T
Much of the data on the acceptability of HIV Pre-Exposure Prophylaxis (PrEP) is based on willingness to take PrEP (i.e., hypothetical receptivity) rather than actual intentions (i.e., planned behavioral action) to do so. We sought to examine differences between hypothetical willingness and behavioral intentions to begin PrEP in a national sample of gay and bisexual men (GBM) across the U.S. We utilized data collected in 2015 to examine differences between those Unwilling (42.6% n = 375), Willing but not intending (41.4%, n = 365), and willing and Intending to take PrEP (15.9%, n = 140) in a multivariable, multinomial logistic regression. Men with less education had higher odds of Intending to take PrEP. Compared to men unsure about PrEP's efficacy, those who believed PrEP was at least 90% efficacious had higher odds of Intending to take PrEP. Those who saw themselves as appropriate candidates for PrEP had higher odds of Intending to take PrEP while those who saw themselves as inappropriate candidates for PrEP had lower odds of Intending to take PrEP in comparison to men unsure if they were appropriate candidates. Increased motivation for condom non-use because of perceived sexual pressure by partners was associated with higher odds of Intending to take PrEP. The groups did not differ by risk behavior nor recent STI diagnosis. Overall, the distinction between willingness and intentions to take PrEP was meaningful and may help explain disparities between PrEP acceptability and uptake. While much of the literature has focused on hypothetical willingness to take PrEP, these results highlight the importance of simultaneously assessing willingness and intentions when examining correspondence with uptake and developing interventions to increase PrEP uptake. Copyright © 2016 Elsevier Ltd. All rights reserved.
"Since both of us are using antiretrovirals, we have been supportive to each other": facilitators and barriers of pre-exposure prophylaxis use in heterosexual HIV serodiscordant couples in Kisumu, Kenya.
Patel, Rena C; Stanford-Moore, Gaelen; Odoyo, Josephine; Pyra, Maria; Wakhungu, Imeldah; Anand, Keerthana; Bukusi, Elizabeth A; Baeten, Jared M; Brown, Joelle M
Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful
Mimiaga, Matthew J; Closson, Elizabeth F; Battle, Shanice; Herbst, Jeffrey H; Denson, Damian; Pitts, Nicole; Holman, Jeremy; Landers, Stewart; Mansergh, Gordon
Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada ® ) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the Pr
Hoagland, Brenda; Moreira, Ronaldo I; De Boni, Raquel B; Kallas, Esper G; Madruga, José Valdez; Vasconcelos, Ricardo; Goulart, Silvia; Torres, Thiago S; Marins, Luana M S; Anderson, Peter L; Luz, Paula M; Costa Leite, Iuri da; Liu, Albert Y; Veloso, Valdilea G; Grinsztejn, Beatriz
The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350-699 fmol/punch and ≥700 fmol/punch). 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08-2.94). The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to
Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians.
Palummieri, Antonio; De Carli, Gabriella; Rosenthal, Éric; Cacoub, Patrice; Mussini, Cristina; Puro, Vincenzo
Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in
Shrestha, Roman; Karki, Pramila; Altice, Frederick L; Huedo-Medina, Tania B; Meyer, Jaimie P; Madden, Lynn; Copenhaver, Michael
Although people who use drugs (PWUD) are key populations recommended to receive pre-exposure prophylaxis (PrEP) to prevent HIV, few data are available to guide PrEP delivery in this underserved group. We therefore examined the willingness to initiate PrEP and the anticipation of HIV risk reduction while on PrEP among high-risk PWUD. In a cross-sectional study of 400 HIV-negative, opioid dependent persons enrolled in a methadone program and reporting recent risk behaviors, we examined independent correlates of being willing to initiate PrEP. While only 72 (18%) were aware of PrEP, after being given a description of it, 251 (62.7%) were willing to initiate PrEP. This outcome was associated with having neurocognitive impairment (aOR=3.184, p=0.004) and higher perceived HIV risk (aOR=8.044, p<0.001). Among those willing to initiate PrEP, only 12.5% and 28.2%, respectively, indicated that they would always use condoms and not share injection equipment while on PrEP. Consistent condom use was associated with higher income (aOR=8.315, p=0.016), always using condoms with casual partners (aOR=6.597, p=0.001), and inversely associated with ongoing drug injection (aOR=0.323, p=0.027). Consistent safe injection, however, was inversely associated with age (aOR=0.948, p=0.035), ongoing drug injection (aOR=0.342, p<0.001), and perceived HIV risk (aOR=0.191, p=0.019). While willingness to initiate PrEP was high and correlated with being at elevated risk for HIV, anticipated higher risk behaviors in this group even while on PrEP suggests that the next generation of HIV prevention approaches may need to combine biomedical and behavioral components to sustain HIV risk reduction over time. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors.We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice--once as if they were taking PrEP and once as if they were not taking PrEP--within four risk situations (vignettes. They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette.We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01 and with the within-subject comparison (-0.31, p < 0.001. Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP.Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention.
Zablotska, Iryna B; Selvey, Christine; Guy, Rebecca; Price, Karen; Holden, Jo; Schmidt, Heather-Marie; McNulty, Anna; Smith, David; Jin, Fengyi; Amin, Janaki; Cooper, David A; Grulich, Andrew E
The New South Wales (NSW) HIV Strategy 2016-2020 aims for the virtual elimination of HIV transmission in NSW, Australia, by 2020. Despite high and increasing levels of HIV testing and treatment since 2012, the annual number of HIV diagnoses in NSW has remained generally unchanged. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV infection among gay and bisexual men (GBM) when taken appropriately. However, there have been no population-level studies that evaluate the impact of rapid PrEP scale-up in high-risk GBM. Expanded PrEP Implementation in Communities in NSW (EPIC-NSW) is a population-level evaluation of the rapid, targeted roll-out of PrEP to high-risk individuals. EPIC-NSW, is an open-label, single-arm, multi-centre prospective observational study of PrEP implementation and impact. Over 20 public and private clinics across urban and regional areas in NSW have participated in the rapid roll-out of PrEP, supported by strong community mobilization and PrEP promotion. The study began on 1 March 2016, aiming to enroll at least 3700 HIV negative people at high risk of HIV. This estimate took into consideration criteria for PrEP prescription in people at high risk for acquiring HIV as defined in the NSW PrEP guidelines. Study participants receive once daily co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and are followed for up to 24 months. Follow-up includes: testing for HIV at 1 month, HIV and other sexually transmissible infections three-monthly, HCV annually and monitoring of renal function six-monthly. Optional online behavioural surveys are conducted quarterly. The co-primary endpoints are (i) HIV diagnoses and incidence in the cohort and (ii) HIV diagnoses in NSW. EPIC-NSW is a population-based PrEP implementation trial which targets the entire estimated population of GBM at high risk for HIV infection in NSW. It will provide a unique opportunity to evaluate the population impact of PrEP on a concentrated HIV
Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa
Background Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Methods Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Results Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18–25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. Conclusion These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health
Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa
Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18-25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities.
Full Text Available Recent clinical trials suggest that pre-exposure prophylaxis (PrEP may reduce HIV transmission by up to 86% for men who have sex with men (MSM, whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK, using a mixed methods design.Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically.Under one third (29.7% of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8% were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18-25 years and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use.These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity, as well as to responding to the diverse informational and sexual health needs of all MSM communities.
Young, Ingrid; Flowers, Paul; McDaid, Lisa M
To explore the acceptability of pre-exposure prophylaxis (PrEP) among gay, bisexual and men who have sex with men (MSM) and migrant African communities in Scotland, UK. Consecutive mixed qualitative methods consisting of focus groups (FGs) and in-depth interviews (IDIs) explored PrEP acceptability. Data were digitally recorded, transcribed and analysed thematically to identify anticipated and emerging themes. Participants were recruited through community sexual health and outreach support services, and from non-sexual health settings across Scotland. Inclusion criteria included identification as either MSM and/or from migrant African communities; 18 years and older; living in Scotland at the time of participation. 7 FGs were conducted (n=33): 5 with MSM (n=22) and 2 mixed-sex groups with African participants (n=11, women=8), aged 18-75 years. 34 IDIs were conducted with MSM (n=20) and African participants (n=14, women=10), aged 19-60 years. The sample included participants who were HIV-positive and HIV-negative or untested (HIV-positive FG participants, n=22; HIV-positive IDI participants, n=17). Understandings of PrEP effectiveness and concerns about maintaining regular adherence were identified as barriers to potential PrEP uptake and use. Low perception of HIV risk due to existing risk management strategies meant few participants saw themselves as PrEP candidates. Participants identified risk of other sexually transmitted infections and pregnancy as a concern which PrEP did not address for either themselves or their sexual partners. PrEP emerged as a contentious issue because of the potentially negative implications it had for HIV prevention. Many participants viewed PrEP as problematic because they perceived that others would stop using condoms if PrEP was to become available. PrEP implementation needs to identify appropriate communication methods in the context of diverse HIV literacy; address risk-reduction concerns and; demonstrate how PrEP can be part of a
The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.
Hannaford, Alisse; Lipshie-Williams, Madeleine; Starrels, Joanna L; Arnsten, Julia H; Rizzuto, Jessica; Cohen, Phillip; Jacobs, Damon; Patel, Viraj V
Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional
Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.
Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott
In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a
Young, Lindsay E; Schumm, Phil; Alon, Leigh; Bouris, Alida; Ferreira, Matthew; Hill, Brandon; Khanna, Aditya S; Valente, Thomas W; Schneider, John A
Advances in biomedical prevention strategies such as pre-exposure prophylaxis (PrEP) represent a new opportunity for reducing HIV incidence among young Black men who have sex with men, for whom the number of new HIV infections continues to rise. However, studies have documented low rates of PrEP uptake in this community. Research suggests that the peer networks of young Black men who have sex with men play important roles in their sexual health decisions. PrEP Chicago is a randomized controlled trial network intervention designed to increase PrEP uptake among young Black men who have sex with men living in Chicago. The aims of this study are twofold. Aim 1 is to estimate the effectiveness of a peer change agent intervention for (1) increasing the number of referrals made to a PrEP information line, (2) increasing the rate of PrEP adoption among non-participant peers, and (3) increasing PrEP knowledge, attitudes, and intentions among participants. Aim 2 is to determine the individual and network variables that explain peer change agent effectiveness. PrEP Chicago is a social network intervention that utilizes the influence of peer change agents to link young Black men who have sex with men in Chicago to PrEP. Young Black men who have sex with men were recruited using respondent-driven sampling. Once screened for eligibility, participants were randomly assigned to either one of two treatment sequences: (1) intervention treatment in Year 1 followed by a minimal contact attention control in Year 2 or (2) the minimal contact attention control in Year 1 followed by treatment in Year 2. The treatment consists of a PrEP/peer change agent training workshop followed by booster calls for 12 months. The attention control consists of a sex diary activity designed to help participants assess sexual risk. Psychosocial, sexual health, and network data are collected from all participants at baseline and at 12- and 24-month follow-ups. In total, 423 participants aged 18-35 have
Gallagher, Timothy; Link, Lauren; Ramos, Michael; Bottger, Edward; Aberg, Judith; Daskalakis, Demetre
The purpose of this study was to evaluate the ability of men who have sex with men (MSM) testing for HIV at commercial sex venues to assess the following: their candidacy for pre-exposure chemoprophylaxis (PrEP) as defined by meeting entry criteria for the iPrEx (Iniciativa Profilaxis Pre-Exposición) phase III clinical trial of PrEP, and their perception of their own HIV risk and candidacy for PrEP. Interviewers surveyed 629 MSM at three NYC commercial sex venues from June 2011 through June 2012. Questions focused on demographics, sexual activity, and drug use in the three months prior to testing, as well as perceived risk of HIV acquisition and perceived candidacy for PrEP use. Data were analyzed by Chi square and Fisher's exact test. Results show that a majority of clients (80.3%) met entry criteria for the iPrEX. Most of these men (78.0%), however, did not perceive their risk to be significant enough to warrant PrEP use (P=.000). Factors were identified which associated with a risk perception that correlated with eligibility for iPrEX.
... than 70%. Your risk of getting HIV from sex can be even lower if you combine PrEP with condoms and other prevention methods. Download PrEP 101 Consumer Info Sheet Vital Signs Fact Sheet on Daily Pill Can Prevent HIV (PrEP) Expand All Collapse All Video Introductions to PrEP What is PrEP? A Brief ...
Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C
When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.
Decline in bone mass with tenofovir disoproxil fumarate/emtricitabine is associated with hormonal changes in the absence of renal impairment when used by HIV uninfected adolescent boys and young men for HIV pre-exposure
Background. We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. Methods. In a study of daily TDF/emtricitabine (FTC) pre-exposure prophylaxis (PrEP) in HIV uninfected young men who have sex with men, we measured ch...
Research Council show that women aged 15 - 25 years are most at risk of contracting HIV. This report appears to have been one of the catalysts in prompting the Higher Education and Training HIV/. AIDS Programme (HEAIDS) and the National Department of Health to roll out Truvada to university and college students, ...
Weber, David J; Rutala, William A
Health care personnel are commonly exposed to infectious agents via sharp injuries (eg, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus), direct patient care (eg, pertussis and meningococcus), and the contaminated environment (eg, Clostridium difficile). An effective occupational program is a key aspect of preventing acquisition of an infection by offering the following: (1) education of health care personnel regarding proper handling of sharps, early identification and isolation of potentially infectious patients, and hand hygiene; (2) assuring immunity to vaccine-preventable diseases; and, (3) immediate availability of a medical evaluation after a nonprotected exposure to an infectious disease. Copyright © 2016 Elsevier Inc. All rights reserved.
Postma, MJ; Londeman, J; Veenstra, M; de Walle, HEK; de Jong-van den Berg, LTW
Background: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns - such as spina bifida - and possibly other congenital malformations. Objective. To estimate cost effectiveness of periconceptional supplementation of folk: acid
Malaria D:lay still be contracted despite good cOD:lpliance with ... true that prophylaxis is always better than no prophy- laxis, nor is ... If used during pregnancy, a folic acid supplement ... include folate deficiency, agranulocytosis, illegaloblastic.
Thomas S A Wallis
Full Text Available BACKGROUND: Motion-defined form can seem to persist briefly after motion ceases, before seeming to gradually disappear into the background. Here we investigate if this subjective persistence reflects a signal capable of improving objective measures of sensitivity to static form. METHODOLOGY/PRINCIPAL FINDINGS: We presented a sinusoidal modulation of luminance, masked by a background noise pattern. The sinusoidal luminance modulation was usually subjectively invisible when static, but visible when moving. We found that drifting then stopping the waveform resulted in a transient subjective persistence of the waveform in the static display. Observers' objective sensitivity to the position of the static waveform was also improved after viewing moving waveforms, compared to viewing static waveforms for a matched duration. This facilitation did not occur simply because movement provided more perspectives of the waveform, since performance following pre-exposure to scrambled animations did not match that following pre-exposure to smooth motion. Observers did not simply remember waveform positions at motion offset, since removing the waveform before testing reduced performance. CONCLUSIONS/SIGNIFICANCE: Motion processing therefore interacts with subsequent static visual inputs in a way that can improve performance in objective sensitivity measures. We suggest that the brief subjective persistence of motion-defined forms that can occur after motion offsets is a consequence of the decay of a static form signal that has been transiently enhanced by motion processing.
Koning, Irene V; Groenenberg, Irene A L; Gotink, Anniek W; Willemsen, Sten P; Gijtenbeek, Manon; Dudink, Jeroen; Go, Attie T J I; Reiss, Irwin K M; Steegers, Eric A P; Steegers-Theunissen, Régine P M
We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks
Full Text Available Anopheles female mosquitoes can transmit Plasmodium, the malaria parasite. During their aquatic life, wild Anopheles mosquito larvae are exposed to a huge diversity of microbes present in their breeding sites. Later, adult females often take successive blood meals that might also carry different micro-organisms, including parasites, bacteria, and viruses. Therefore, prior to Plasmodium ingestion, the mosquito biology could be modulated at different life stages by a suite of microbes present in larval breeding sites, as well as in the adult environment. In this article, we highlight several naturally relevant scenarios of Anopheles microbial pre-exposure that we assume might impact mosquito vectorial competence for the malaria parasite: (i larval microbial exposures; (ii protist co-infections; (iii virus co-infections; and (iv pathogenic bacteria co-infections. In addition, significant behavioral changes in African Anopheles vectors have been associated with increasing insecticide resistance. We discuss how these ethological modifications may also increase the repertoire of microbes to which mosquitoes could be exposed, and that might also influence their vectorial competence. Studying Plasmodium–Anopheles interactions in natural microbial environments would efficiently contribute to refining the transmission risks.
Amoako, Akwasi A; Nafee, Tamer M; Ola, Bolarinde
The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.
Schwartz, Lindsay P; Kearns, David N; Silberberg, Alan
The aim of the present study was to determine how nicotine pre-exposure affects the elasticity of demand for intravenous cocaine and for sucrose pellets in adult male rats. In Experiment 1, demand for cocaine was assessed in rats that had nicotine in their drinking water. Nicotine pre-exposure significantly decreased rats' willingness to defend cocaine consumption as the price (measured as the number of responses per cocaine infusion) increased compared with a control group with no nicotine pre-exposure. That is, nicotine increased the elasticity of demand for cocaine infusions. Experiment 2 repeated the first experiment, but with rats working for sucrose pellets instead of cocaine. Nicotine pre-exposure had no effect on the elasticity of demand for sucrose. This pattern of results suggests that nicotine pre-exposure can reduce the reinforcing effects of cocaine, but not sucrose, in adult male rats.
Koning, I V; Dudink, J; Groenenberg, I A L; Willemsen, S P; Reiss, I K M; Steegers-Theunissen, R P M
STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human
Calabrese, Sarah K; Dovidio, John F; Tekeste, Mehrit; Taggart, Tamara; Galvao, Rachel W; Safon, Cara B; Willie, Tiara C; Caldwell, Abigail; Kaplan, Clair; Kershaw, Trace S
PrEP uptake has lagged among US women. PrEP stigma is a recognized barrier to uptake among MSM but remains largely unexplored among women. This study examined the pervasiveness of PrEP stigma among US women and its implications for uptake. Setting/Methods: In a 2017 online survey of Planned Parenthood patients drawn from the three cities with the highest numbers of new HIV infections in Connecticut, 597 heterosexually-active, HIV-negative, PrEP-inexperienced women reported background characteristics, two dimensions of anticipated PrEP stigma (PrEP-user stereotypes and PrEP disapproval by others), and three indicators of potential PrEP uptake (interest in learning more about PrEP, intention to use PrEP, and comfort discussing PrEP with a provider). Participants commonly perceived PrEP-user stereotypes, with many believing that others would regard them as promiscuous (37%), HIV-positive (32%), bad (14%), or gay (11%) if they used PrEP. Thirty percent would feel ashamed to disclose PrEP use. Many participants expected disapproval by family (36%), sex partners (34%), and friends (25%). In adjusted analyses, perception of PrEP-user stereotypes was uniquely associated with lower comfort discussing PrEP with a provider. Expected PrEP disapproval by others was uniquely associated with less PrEP interest, less intention to use PrEP, and less comfort discussing PrEP with a provider. Exploratory moderation analyses suggested intention to use PrEP was greatest when participants anticipated low levels of both PrEP-user stereotypes and PrEP disapproval by others. Findings highlight the need for positive messaging targeting potential PrEP users and their social networks to increase PrEP acceptance and uptake.
C?ceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter
Introduction: Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that...
Geary, Cynthia W; Bukusi, Elizabeth A; Geary, Cynthia W; Bukusi, Elizabeth A; van der Straten, Ariane; Stadler, Jonathan; Luecke, Ellen; Laborde, Nicole; Hartmann, Miriam; Montgomery, Elizabeth T; Corneli, Amy L; McKenna, Kevin; Headley, Jennifer; Ahmed, Khatija; Odhiambo, Jacob
Introduction Risk perception is a core construct in many behaviour change theories in public health. Individuals who believe they are at risk of acquiring an illness may be more likely to engage in behaviours to reduce that risk; those who do not feel at risk may be unlikely to engage in risk reduction behaviours. Among participants who seroconverted in two FEM-PrEP sites – Bondo, Kenya, and Pretoria, South Africa – we explored perceived HIV risk and worry about acquiring HIV prior to HIV inf...
at Initiation of Sexual Activity Correct & Consistent Condom Use Prevention of mother-to- child transmission July 16, 2012: FDA approves...Okulicz JF, Medicine 2016 PrEP Utilization in a Managed Care System (Kaiser Permanente) 1200 ~ 1045 1000 . 800 600 . 400 200 0 835 657 0
Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J.; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B.; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya
PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online-to-Offline (O2O) model
C. Van Tienen (Carla); D.A.M.C. van de Vijver (David); T. Noori (Teymur); A. Sonnerborg (Anders); C.A.B. Boucher (Charles)
markdownabstract__To the editor:__ In a recent paper by Hauser et al. in this journal, a prevalence of 10.8% of transmitted drugresistant viruses was reported among newly diagnosed HIV cases in Germany in 2013 and 2014. The authors conclude that genotypic resistance testing remains important for
1 Sugiharto et al.: Aedes aegypti blood- Michael J. Turell 1 feeding after DEET pre-exposure Virology Division, USAMRIID 2 1425 Porter...Pre-exposure to DEET on the Downstream Blood-Feeding Behaviors of 9 Aedes aegypti Mosquitoes1 10 11 Victor A. Sugiharto,2 John P. Grieco,2,3...insect behavior for disease prevention. However, genetic insensitivity and 31 habituation in Aedes aegypti (L.) mosquitoes after pre-exposure to DEET
Michael Todd Allen
Full Text Available Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from CS or US alone pre-exposures (Holloway et al., 2012. US alone pre-exposures disrupt subsequent CR acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al., (2012 reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioural Inhibition (AMBI. Sixty six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI individuals exhibited enhanced proactive interference as compared to non-inhibited (NI individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible learned helplessness. Applications of these findings of
Sevenster, D.; de Oliveira Alvares, L.; D'Hooge, R.
The degree of generalization from a fearful context to other contexts is determined by precision of the original fear memory. Experiences before and after fear learning affect memory precision. Pre-exposure to a similar context before context conditioning results in increased generalization to the
Full Text Available Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease.This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA was used to analyse the data.Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful.The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.
de Jong-van den Berg, LTW; Hernandez-Diaz, S; Werler, MM; Louik, C; Mitchell, AA
Objective: The purpose of this study was to describe recent trends in folic acid awareness and use in the periconceptional period among pregnant women in relation to maternal sociodemographic and other relevant factors. Study design: From 1988 to 2002, 16,555 women from the Slone Epidemiology Center
Full Text Available Binta Sultan,1,2 Paul Benn,1 Laura Waters1 1Department of Genitourinary Medicine, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK; 2Centre for Sexual Health and HIV Research, University College London, London, UK Abstract: The incidence of human immunodeficiency virus (HIV infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP is the use of short-term antiretroviral therapy (ART to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE, has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines. Keywords: post-exposure prophylaxis, pre-exposure prophylaxis, treatment as prevention, human immunodeficiency virus
Zhang, S; Rattanatray, L; McMillen, I C; Suter, C M; Morrison, J L
Women entering pregnancy with a high body weight and fat mass have babies at increased risk of becoming overweight or obese in childhood and later life. It is not known, whether exposure to a high level of maternal nutrition before pregnancy and exposure to a high transplacental nutrient supply in later pregnancy act through similar mechanisms to program later obesity. Using the pregnant sheep we have shown that maternal overnutrition in late pregnancy results in an upregulation of PPARγ activated genes in fetal visceral fat and a subsequent increase in the mass of subcutaneous fat in the postnatal lamb. Exposure to maternal overnutrition during the periconceptional period alone, however, results in an increase in total body fat mass in female lambs only with a dominant effect on visceral fat depots. Thus the early programming of later obesity may result from 'two hits', the first occurring as a result of maternal overnutrition during the periconceptional period and the second occurring as a result of increased fetal nutrition in late pregnancy. Whilst a short period of dietary restriction during the periconceptional period reverses the impact of periconceptional overnutrition on the programming of obesity, it also results in an increased lamb adrenal weight and cortisol stress response, together with changes in the epigenetic state of the insulin like growth factor 2 (IGF2) gene in the adrenal. Thus, not all of the effects of dietary restriction in overweight or obese mother in the periconceptional period may be beneficial in the longer term. Copyright © 2010 Elsevier Ltd. All rights reserved.
Koning, I V; Baken, L; Groenenberg, I A L; Husen, S C; Dudink, J; Willemsen, S P; Gijtenbeek, M; Koning, A H J; Reiss, I K M; Steegers, E A P; Steegers-Theunissen, R P M
Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. Fetal growth is influenced by periconceptional maternal conditions. We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P head measured by HC and HV (All ITALIC! P head may be of benefit in future early antenatal care. This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email
Bertucci, Frédéric; Matos, Ricardo Jorge Santa Clara; Dabelsteen, Torben
aggressively during subsequent disputes. This phenomenon is known as aggressive priming. The aim of our study was to investigate if this priming response follows a step function, i.e. appears only above a threshold level of aggression witnessed by a bystander. We found that bystanders behaved more aggressively...... in subsequent interactions when pre-exposed to an aggressive conspecific that was engaged in a fight whatever the level of aggression this fight reached. However, bystanders’ behaviour after pre-exposure was not correlated to the previously witnessed level of aggressiveness. These results suggest...... that individuals alter their behaviour in an aggressive social environment and indicate that priming effect follows a step function where aggression is triggered by an aggressive context. We discuss our results and the effect of pre-exposure on agonistic interactions in a communication network perspective....
Zhang Lianzhen; Deng Zhicheng
The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)
Nguyen, David; Schumacher, Anett; Erb, Suzanne; Ito, Rutsuko
Addiction is characterized by persistence to seek drug reinforcement despite negative consequences. Drug-induced aberrations in approach and avoidance processing likely facilitate the sustenance of addiction pathology. Currently, the effects of repeated drug exposure on the resolution of conflicting approach and avoidance motivational signals have yet to be thoroughly investigated. The present study sought to investigate the effects of cocaine pre-exposure on conflict resolution using novel approach-avoidance paradigms. We used a novel mixed-valence conditioning paradigm to condition cocaine-pre-exposed rats to associate visuo-tactile cues with either the delivery of sucrose reward or shock punishment in the arms in which the cues were presented. Following training, exploration of an arm containing a superimposition of the cues was assessed as a measure of conflict resolution behavior. We also used a mixed-valence runway paradigm wherein cocaine-pre-exposed rats traversed an alleyway toward a goal compartment to receive a pairing of sucrose reward and shock punishment. Latency to enter the goal compartment across trials was taken as a measure of motivational conflict. Our results reveal that cocaine pre-exposure attenuated learning for the aversive cue association in our conditioning paradigm and enhanced preference for mixed-valence stimuli in both paradigms. Repeated cocaine pre-exposure allows appetitive approach motivations to gain greater influence over behavioral output in the context of motivational conflict, due to aberrant positive and negative incentive motivational processing.
Goldhaber, Samuel Z.
Mechanical measures such as graduated compression stockings and intermittent compression boots are available for venous thrombosis prophylaxis, but compliance may be limited. Plantar venous pneumatic compression devices have attained widespread acceptance by both patients and nurses because of their comfort and compact size, but their track record for efficacy is poor. Inferior vena cava filters prevent pulmonary embolism, but do not halt the thrombotic process or prevent venous thrombosis. Pharmacologic prophylaxis traditionally has relied upon minidose unfractionated heparin; however, re-examination is warranted in the face of increasingly ill and complex patients. My opinion is that small, fixed doses of once-daily low molecular weight heparin will eventually replace minidose unfractionated heparin as the standard pharmacologic prophylaxis regimen for most surgical and medical patients. Prolongation of prophylaxis after hospital discharge should receive increased emphasis. Most patients being transferred to a skilled nursing facility should receive venous thromboembolism prophylaxis. Similarly, most patients undergoing total hip or knee replacement should receive prolonged preventive regimens, with at least 1 month of anticoagulation. Despite advances, certain aspects of venous thrombosis prophylaxis remain problematic. First, a surprisingly high number of hospitalized patients develop venous thrombosis because of failed (rather than omitted) prophylaxis. Second, many patients in intensive care have a combination of peripheral vascular disease and active bleeding (usually gastrointestinal) that precludes mechanical or pharmacologic prophylaxis. Third, neurosurgical patients undergoing craniotomy for brain tumors suffer a high rate of venous thrombosis and major pulmonary embolism despite the routine use of combined mechanical and pharmacologic prophylaxis. My opinion is that these three areas, in addition to the hospital culture of prophylaxis, should receive
Allen, Michael Todd; Miller, Daniel P
Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from conditioned stimulus (CS) or unconditioned stimulus (US) alone pre-exposures (Holloway et al., 2012). US alone pre-exposures disrupt subsequent conditioned response (CR) acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al. (2012) reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioral Inhibition (AMBI). Sixty-six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI) individuals exhibited enhanced proactive interference as compared to non-inhibited (NI) individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible
Full Text Available Abstract Background Despite strong evidence of the benefits of preconception interventions to improve pregnancy outcomes, the delivery and uptake of preconception care in general and periconceptional folate supplementation in particular remains low. The aim of this study was to determine women's views of the barriers and enablers to the uptake of preconception care and periconceptional folate supplementation. Methods Focus groups were undertaken in 2007 with 17 women of reproductive age (18-45 years. To identify key issues and themes within the data, focus groups were analysed using an inductive process of thematic analysis. Results Most women were unaware of the need to attend for preconception care and were surprised at the breadth of issues involved. Women also felt general practitioners (GPs should be more proactive in promoting preconception care availability but acknowledged that they themselves had to be thinking about pregnancy or becoming pregnant to be receptive to it. Barriers to periconceptional folate supplementation included confusion about reasons for use, dose, duration, timing and efficacy of folate use. Enablers included the desire to do anything they could to ensure optimum pregnancy outcomes, and promotional material and letters of invitation from their GP to advise them of the availability and the need for preconception care. Conclusion A number of important barriers and enablers exist for women regarding the delivery and uptake of preconception care and periconceptional folate supplementation. It is essential that these patient perspectives are addressed in both the implementation of evidence based clinical practice guidelines and in the systematic design of an intervention to improve preconception care delivery.
Investigating Potential Effects of Dengue Virus Infection and Pre-exposure to DEET on Aedes aegypti Behaviors by Victor A...exposure to DEET on Aedes aegypti Behaviors" Name of Candidate: Victor Sugiharto Doctor of Philosophy Degree February 5, 2016 DISSERTATION AND...Infection and Pre-exposure to DEET on Aedes aegypti Behaviors" is appropriately acknowledged and. beyond brief excerpts , is with the permission of
Full Text Available The study reported four experiments aiming to test the effects of the pre-exposure schedule and water deprivation on the generalization of a conditioned taste aversion in rats, with a particular focus on testing whether or not the concurrent schedule might enhance generalization. In two experiments, non-water-deprived rats received concurrent, intermixed, or blocked exposure to a sweet-acid solution and a salty-acid solution before conditioning of one of these compounds and testing of both flavors. During pre-exposure, the rats consumed a greater amount of the sweet-acid solution than the salty-acid solution (Experiments 1 and 2, consumption of the former increasing during pre-exposure while consumption of the latter decreased (Experiment 1. Furthermore, consumption of the salty-acid solution was lower during concurrent than intermixed or blocked pre-exposure (Experiment 1 and 2 while consumption of the sweet-acid solution was greater during intermixed than concurrent or blocked pre-exposure (Experiment 1. It is discussed whether the pre-exposure schedule might modify stimulus perception beyond the mere enhancement of stimulus differentiation, by, for instance, affecting the palatability of gustatory stimuli. Evidence for enhanced generalization after concurrent pre-exposure was not found for either deprived (Experiments 1, 2, and 3 or non-deprived rats (Experiments 3 and 4, with deprivation leading to a general increase in consumption of both the conditioned and test flavors. This then raised the question of whether or not concurrent pre-exposure to flavors always increases generalization between them. The present study highlights the importance of this issue for various accounts of perceptual learning.
Sandoval-Chagoya, Gloria Alejandra; Laniado-Laborín, Rafael
Background: despite the proven effectiveness of preventive therapy for deep vein thrombosis, a significant proportion of patients at risk for thromboembolism do not receive prophylaxis during hospitalization. Our objective was to determine the adherence to thrombosis prophylaxis guidelines in a general hospital as a quality control strategy. Methods: a random audit of clinical charts was conducted at the Tijuana General Hospital, Baja California, Mexico, to determine the degree of adherence to deep vein thrombosis prophylaxis guidelines. The instrument used was the Caprini's checklist for thrombosis risk assessment in adult patients. Results: the sample included 300 patient charts; 182 (60.7 %) were surgical patients and 118 were medical patients. Forty six patients (15.3 %) received deep vein thrombosis pharmacologic prophylaxis; 27.1 % of medical patients received deep vein thrombosis prophylaxis versus 8.3 % of surgical patients (p < 0.0001). Conclusions: our results show that adherence to DVT prophylaxis at our hospital is extremely low. Only 15.3 % of our patients at risk received treatment, and even patients with very high risk received treatment in less than 25 % of the cases. We have implemented strategies to increase compliance with clinical guidelines.
Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.
In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607
Matthews, Lynn T; Ribaudo, Heather B; Kaida, Angela; Bennett, Kara; Musinguzi, Nicholas; Siedner, Mark J; Kabakyenga, Jerome; Hunt, Peter W; Martin, Jeffrey N; Boum, Yap; Haberer, Jessica E; Bangsberg, David R
HIV-infected women risk sexual and perinatal HIV transmission during conception, pregnancy, childbirth, and breastfeeding. We compared HIV-1 RNA suppression and medication adherence across periconception, pregnancy, and postpartum periods, among women on antiretroviral therapy (ART) in Uganda. We analyzed data from women in a prospective cohort study, aged 18-49 years, enrolled at ART initiation and with ≥1 pregnancy between 2005 and 2011. Participants were seen quarterly. The primary exposure of interest was pregnancy period, including periconception (3 quarters before pregnancy), pregnancy, postpartum (6 months after pregnancy outcome), or nonpregnancy related. Regression models using generalized estimating equations compared the likelihood of HIV-1 RNA ≤400 copies per milliliter, pregnancy, and 89% of postpartum visits, and was more likely during periconception (adjusted odds ratio, 2.15) compared with nonpregnant periods. Average ART adherence was 90% [interquartile range (IQR), 70%-98%], 93% (IQR, 82%-98%), 92% (IQR, 72%-98%), and 88% (IQR, 63%-97%) during nonpregnant, periconception, pregnant, and postpartum periods, respectively. Average adherence pregnancy were virologically suppressed at most visits, with an increased likelihood of suppression and high adherence during periconception follow-up. Increased frequency of 72-hour gaps suggests a need for increased adherence support during postpartum periods.
Freitas, Rosa; Coppola, Francesca; Henriques, Bruno; Wrona, Fredrick; Figueira, Etelvina; Pereira, Eduarda; Soares, Amadeu M V M
The degree to which marine invertebrate populations can tolerate extreme weather events, such as short-term exposure to high temperatures, and the underlying biochemical response mechanisms are not yet fully understood. Furthermore, scarce information is available on how marine organisms respond to the presence of pollutants after exposure to heat stress conditions. Therefore, the present study aimed to understand how the mussel Mytilus galloprovincialis responds to Hg pollution after pre-exposure to warming conditions. Mussels were exposed to control (17°C) and warming (21°C) conditions during 14days, followed by Hg contamination during 28days under different temperature regimes (17 and 21°C). The results obtained demonstrated significantly higher Hg concentrations in mussels under 17°C during the entire experiment than in organisms exposed to 21°C during the same period, which resulted in higher oxidative stress in mussels under control temperature. Significantly higher Hg concentrations were also observed in mussels pre-exposed to 21°C followed by a 17°C exposure comparing with organisms maintained the entire experiment at 21°C. These results may be explained by higher metabolic capacity in organisms exposed to 17°C after pre-exposure to 21°C that although induced antioxidant defences were not enough to prevent oxidative stress. No significant differences in terms of Hg concentration were found between mussels exposed to 17°C during the entire experiment and organisms pre-exposed to 21°C followed by a 17°C exposure, leading to similar oxidative stress levels in mussels exposed to both conditions. Therefore, our findings demonstrated that pre-exposure to warming conditions did not change mussels' accumulation and tolerance to Hg in comparison to Hg contaminated mussels maintained at control temperature. Furthermore, the present study indicate that organisms maintained under warming conditions for long periods may prevent the accumulation of
Duh, Helen Inseng; Grubliauskiene, Aiste; Dewitte, Siegfried
It has been suggested that the consumption of unhealthy Westernized diet in a context of poverty and resultant food insecurity may have contributed to South-Africa's status of the third fattest country in the World. Considering that a number of South-Africans are reported to have experienced, or are still experiencing food insecurity, procedures which have been shown to reduce the consumption of unhealthy food in higher income countries may be ineffective in South-Africa. We thus tested the robustness of the so called pre-exposure procedure in South-Africa. We also tested the moderating role of childhood poverty in the pre-exposure procedure. With the pre-exposure procedure, a respondent is exposed to a tempting unhealthy food (e.g. candy) in a context that is designed such that eating the food interferes with a task goal. The typical result is that this procedure spills over and reduces consumption of similar tempting food later on. An experimental study conducted in a South-African laboratory showed that the pre-exposure effect is robust even with a sample, where food insecurity prevails. Childhood poverty did not moderate the effect. This study proves that behavioral procedures aimed at reducing the consumption of unhealthy food would be valuable in less rich non-Western countries. Further testing of the robustness of the pre-exposure effect is however recommended in other poorer food insecure countries. Copyright © 2015 Elsevier Ltd. All rights reserved.
Barot, Sabiha K; Bernstein, Ilene L
Taste novelty can strongly modulate the speed and efficacy of taste aversion learning. Novel sweet tastes enhance c-Fos-like immunoreactivity (FLI) in the central amygdala and insular cortex. The present studies examined whether this neural correlate of novelty extends to different taste types by measuring FLI signals after exposure to novel and familiar polysaccharide (Polycose) and salt (NaCl) tastes. Novel Polycose not only failed to elevate FLI expression in central amygdala and insular cortex, but also failed to induce stronger taste aversion learning than familiar Polycose. Novel NaCl, on the other hand, showed patterns of FLI activation and aversion learning similar to that of novel sweet tastes. Possible reasons for the resistance of Polycose to typical pre-exposure effects are discussed. Copyright (c) 2006 APA, all rights reserved.
Nohr, Ellen A; Olsen, Jorn; Bech, Bodil H; Bodnar, Lisa M; Olsen, Sjurdur F; Catov, Janet M
Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known. We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (excess risk further. Whereas regular users of multivitamins (4-6 weeks of 6) before conception had more early losses [HR 1.29 (1.12-1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39-1.09)]. Folate-only use was not associated with fetal death. Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations.
ten Haaft, P.; Cornelissen, M.; Goudsmit, J.; Koornstra, W.; Dubbes, R.; Niphuis, H.; Peeters, M.; Thiriart, C.; Bruck, C.; Heeney, J. L.
Many reports indicate that a long-term asymptomatic state following human immunodeficiency virus type 1 (HIV-1) infection is associated with a low amount of circulating virus. To evaluate the possible effect of stabilizing a low virus load by non-sterilizing pre-exposure vaccination, a quantitative
Grangeiro, Alexandre; Couto, Márcia Thereza; Peres, Maria Fernanda; Luiz, Olinda; Zucchi, Eliana Miura; de Castilho, Euclides Ayres; Estevam, Denize Lotufo; Alencar, Rosa; Wolffenbüttel, Karina; Escuder, Maria Mercedes; Calazans, Gabriela; Ferraz, Dulce; Arruda, Érico; Corrêa, Maria da Gloria; Amaral, Fabiana Rezende; Santos, Juliane Cardoso Villela; Alvarez, Vivian Salles; Kietzmann, Tiago
Few results from programmes based on combination prevention methods are available. We propose to analyse the degree of protection provided by postexposure prophylaxis (PEP) for consensual sexual activity at healthcare clinics, its compensatory effects on sexual behaviour; and the effectiveness of combination prevention methods and pre-exposure prophylaxis (PrEP), compared with exclusively using traditional methods. A total of 3200 individuals aged 16 years or older presenting for PEP at 5 sexually transmitted disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two groups: the PEP group-individuals who come to the clinic within 72 h after a sexual exposure and start PEP; and the non-PEP group-individuals who come after 72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will be conducted initially for 6 months and comprise educational interventions based on information and counselling for using prevention methods, including PrEP. In the second study phase, individuals who remain HIV negative will be regrouped according to the reported use of prevention methods and observed for 18 months: only traditional methods; combined methods; and PrEP. Effectiveness will be analysed according to the incidence of HIV, syphilis and hepatitis B and C and protected sexual behaviour. A structured questionnaire will be administered to participants at baseline and every 6 months thereafter. Qualitative methods will be employed to provide a comprehensive understanding of PEP-seeking behaviour, preventive choices and exposure to HIV. This study will be conducted in accordance with the resolution of the School of Medicine Research Ethics Commission of Universidade de São Paulo (protocol no. 251/14). The databases will be available for specific studies, after management committee approval. Findings will be presented to researchers, health managers and civil society members by means of newspapers, electronic media and scientific journals
Catov, Janet M; Bodnar, Lisa M; Olsen, Jorn; Olsen, Sjurdur; Nohr, Ellen A
The intake of periconceptional multivitamins may decrease the risk of preterm births (PTBs) or small-for-gestational-age (SGA) births. We related the timing and frequency of periconceptional multivitamin use to SGA births and PTBs and its clinical presentations (ie, preterm labor, premature rupture of membranes, and medical induction). Women in the Danish National Birth Cohort (n = 35,897) reported the number of weeks of multivitamin use during a 12-wk periconceptional period. Cox regression was used to estimate the relation between any multivitamin use and PTBs (2 SDs below the mean on the basis of fetal growth curves). The timing (preconception and postconception) and frequency of use were also analyzed. Regular users (4-6 wk) and partial users (1-3 wk) in each period were compared with nonusers. The association between periconceptional multivitamin use and PTBs varied according to prepregnancy overweight status (P-interaction = 0.07). Regular preconception and postconception multivitamin use in women with a prepregnancy BMI (in kg/m(2)) PTBs in nonoverweight women.
Correa, Adolfo; Gilboa, Suzanne M; Botto, Lorenzo D; Moore, Cynthia A; Hobbs, Charlotte A; Cleves, Mario A; Riehle-Colarusso, Tiffany J; Waller, D Kim; Reece, E Albert
The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus. Published by Mosby, Inc.
Jong-van den Berg, L.T.W. de; Walle, H.E.K. de; Pal-de Bruin, K.M. van der; Buitendijk, S.E.; Cornel, M.C.
Objective: In November 1993, Dutch health authorities advised that women planning a pregnancy should take folic acid in the periconceptional period to reduce the risk of fetal neural tube defects. In the autumn of 1995 a national campaign was organized to inform women and health care professionals
de Jong-van den Berg, L. T.; de Walle, H. E.; van der Pal-de Bruin, K. M.; Buitendijk, S. E.; Cornel, M. C.
OBJECTIVE: In November 1993, Dutch health authorities advised that women planning a pregnancy should take folic acid in the periconceptional period to reduce the risk of fetal neural tube defects. In the autumn of 1995 a national campaign was organized to inform women and health care professionals
de Jong-van den Berg, Lolkje Theodora Wilhelmina; de Walle, H.EK; van der Pal-de Bruin, K.M.; Buitendijk, S.E; Cornel, M.C
Objective: In November 1993, Dutch health authorities advised that women planning a pregnancy should take folic acid in the periconceptional period to reduce the risk of fetal neural tube defects. In the autumn of 1995 a national campaign was organized to inform women and health care professionals
Irene V Koning
Full Text Available We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA. Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD, left and right cerebellar diameters (LCD, RCD. Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032-0.280, p<0.05 and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/CRL:β = 0.011mm/mm, 95%CI = 0.005-0.017, p<0.01. Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538-1813 nmol/L. These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child's neurodevelopmental outcome are yet unknown and warrant further investigation.
Emily A Arnold
Full Text Available 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.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.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.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.
Gomez, Gabriela B.; Borquez, Annick; Case, Kelsey K.; Wheelock, Ana; Vassall, Anna; Hankins, Catherine
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
Rena C Patel
Full Text Available The World Health Organization now recommends antiretroviral therapy (ART initiation for all HIV-infected individuals regardless of CD4 cell count or disease status. Understanding the facilitators and barriers to initiation of and adherence to ART is essential to successful scale-up of "universal" ART.To investigate facilitators and barriers to ART initiation, we conducted 44 in-depth individual or couple interviews with 63 participants (33 participants with HIV and 30 without HIV already enrolled in a prospective implementation study of oral antiretroviral-based prevention in Kisumu, Kenya between August and September 2014. A semi-structured interview guided discussions on: 1 perceived advantages and disadvantages of ART; 2 reasons for accepting or declining ART initiation; and 3 influence of prevention of transmission to partner or infant influencing ART use. Transcripts from the interviews were iteratively analyzed using inductive content analysis.HIV-infected participants indicated that living a healthier life, preventing HIV transmission to others, and appearing "normal" or "healthy" again facilitated their initiation of ART. While appearing "normal" allowed these individuals to interact with their communities without stigmatization, they also perceived community opposition to their initiating ART, because appearing "normal" again prevented community members from easily identifying infected individuals in their community. Denial of diagnosis, disclosure stigma, perceived side-effects, and challenges in obtaining refills were additional barriers to ART initiation.Community perceptions play an important role in both facilitating and inhibiting ART initiation. Perceived stigma, including perceived community opposition to widespread ART use, is an important barrier to ART initiation. Addressing such barriers, while capitalizing on facilitators, to ART initiation should be central to universal ART scale-up efforts.
Full Text Available Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM and female sex workers (FSW.MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS. Sexual activity data were collected via daily text message (SMS queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003, while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen.Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens.ClinicalTrials.gov NCT00971230.
Hoornenborg, Elske; Achterbergh, Roel Ca; van der Loeff, Maarten F Schim; Davidovich, Udi; van der Helm, Jannie J; Hogewoning, Arjan; van Duijnhoven, Yvonne Thp; Sonder, Gerard Jb; de Vries, Henry Jc; Prins, Maria
The Amsterdam PrEP project is a prospective, open-label demonstration study at a large sexually transmitted infection (STI) clinic. We examined the uptake of PrEP; the baseline characteristics of men who have sex with men (MSM) and transgender persons initiating PrEP; their choices of daily versus
Arnold, Emily A; Hazelton, Patrick; Lane, Tim; Christopoulos, Katerina A; Galindo, Gabriel R; Steward, Wayne T; Morin, Stephen F
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. 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. 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. 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.
Morin, Stephen; Arnold, EA; Hazelton, P; Lane, T; Christopoulos, KA; Galindo, GR; Steward, WT; Morin, SF
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.
Mutua, Gaudensia; Sanders, Eduard; Mugo, Peter; Anzala, Omu; Haberer, Jessica E; Bangsberg, David; Barin, Burc; Rooney, James F; Mark, David; Chetty, Paramesh; Fast, Patricia; Priddy, Frances H
Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. ClinicalTrials.gov NCT00971230.
Full Text Available With a global estimate of 2.5 million new infections of HIV occurring yearly, discovering novel methods to help stem the spread of the virus is critical. The use of antiretroviral chemoprophylaxis for preventing HIV after accidental or occupational exposure and in maternal to fetal transmission has become a widely accepted method to combat HIV. Based on this success, pre-exposure chemoprophylaxis (PrEP is being explored in at-risk patient populations such as injecting drug users, female sex workers and men who have sex with men. This off-label and unmonitored use has created a need for education and intervention by pharmacists and other healthcare professionals. Pharmacists should educate themselves on PrEP and be prepared to counsel patients about their means of obtaining it (e.g. borrowing or sharing medications and ordering from disreputable Internet pharmacies. They should also be proactive about medication therapy management in these patients due to clinically important drug interactions with PrEP medications. Only one trial exploring the safety and efficacy of tenofovir as PrEP has been completed thus far. However, five ongoing trials are in various stages and two additional studies are scheduled for the near future. Unfortunately, studies in this arena have met with many challenges that have threatened to derail progress. Ethical controversy surrounding post-trial care of participants who seroconvert during studies, as well as concerns over emerging viral resistance and logistical site problems, have already halted several PrEP trials. Information about these early trials has already filtered down to affected individuals who are experimenting with this unproven therapy as an “evening before pill”. The potential for PrEP is promising; however, more extensive trials are necessary to establish its safety and efficacy. Pharmacists are well-positioned to play a key role in helping patients make choices about PrEP, managing their therapy
Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.
Hoyt, Adrienne T; Canfield, Mark A; Romitti, Paul A; Botto, Lorenzo D; Anderka, Marlene T; Krikov, Sergey V; Tarpey, Morgan K; Feldkamp, Marcia L
While associations between secondhand smoke and a few birth defects (namely, oral clefts and neural tube defects) have been noted in the scientific literature, to our knowledge, there is no single or comprehensive source of population-based information on its associations with a range of birth defects among nonsmoking mothers. We utilized data from the National Birth Defects Prevention Study, a large population-based multisite case-control study, to examine associations between maternal reports of periconceptional exposure to secondhand smoke in the household or workplace/school and major birth defects. The multisite National Birth Defects Prevention Study is the largest case-control study of birth defects to date in the United States. We selected cases from birth defect groups having >100 total cases, as well as all nonmalformed controls (10,200), from delivery years 1997 through 2009; 44 birth defects were examined. After excluding cases and controls from multiple births and whose mothers reported active smoking or pregestational diabetes, we analyzed data on periconceptional secondhand smoke exposure-encompassing the period 1 month prior to conception through the first trimester. For the birth defect craniosynostosis, we additionally examined the effect of exposure in the second and third trimesters as well due to the potential sensitivity to teratogens for this defect throughout pregnancy. Covariates included in all final models of birth defects with ≥5 exposed mothers were study site, previous live births, time between estimated date of delivery and interview date, maternal age at estimated date of delivery, race/ethnicity, education, body mass index, nativity, household income divided by number of people supported by this income, periconceptional alcohol consumption, and folic acid supplementation. For each birth defect examined, we used logistic regression analyses to estimate both crude and adjusted odds ratios and 95% confidence intervals for both
Friberg, Anne Katrine Holflod; Jørgensen, Finn Stener
INTRODUCTION: Approximately 60-70 pregnancies are affected by neural tube defects (NTD) in Denmark annually. Folic acid (FA) deficiency can cause NTD. Periconceptional FA supplementation reduces the risk of NTD by up to 70-80%. Danish women planning pregnancy are recommended 0.4 mg of FA daily from...... at least one month before planned conception and continuing throughout the first 12 weeks of pregnancy. The aim of the present study was to examine the knowledge about and use of FA supplementation among Danish pregnant women. METHODS: From 11 October 2012 to 15 November 2012, all women attending...... for a routine nuchal translucency scan were given a questionnaire regarding their knowledge and use of FA supplementation during their current pregnancy. RESULTS: A total of 462 women answered the questionnaire. 95% had taken FA supplements at some point during their pregnancy, but only 10.4% as recommended...
Bülow, Steffen; Kronborg, O
Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....
Parisi, F; Rousian, M; Koning, A H J; Willemsen, S P; Cetin, I; Steegers-Theunissen, R P M
Is periconceptional maternal one-carbon (I-C) metabolism associated with embryonic morphological development in non-malformed ongoing pregnancies? Serum vitamin B12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) are associated with embryonic development according to the Carnegie stages. Derangements in maternal I-C metabolism affect reproductive and pregnancy outcomes, as well as future health of the offspring. Between 2010 and 2014, women with singleton ongoing pregnancies were enrolled in a prospective periconceptional cohort study. A total of 234 pregnancies, including 138 spontaneous or IUI pregnancies with strict pregnancy dating and 96 pregnancies derived from IVF, ICSI or cryopreserved embryo transfer (IVF/ICSI pregnancies), underwent longitudinal transvaginal three-dimensional ultrasound (3D US) scans from 6+0 up to 10+2 weeks of gestation. Carnegie stages were defined using internal and external morphologic criteria in a virtual reality system. Maternal venous blood samples were collected at enrollment for serum vitamin B12, RBC folate and plasma tHcy assessment. Associations between biomarker concentrations and longitudinal Carnegie stages were investigated using linear mixed models. We performed a median of three 3D US scans per pregnancy (range 1-5) resulting in 600 good quality data sets for the Carnegie stage annotation (80.5%). Vitamin B12 was positively associated with embryonic development in the total study population (β = 0.001 (95% CI: 0.000; 0.002), P Carnegie stages only in IVF/ICSI pregnancies (β = 0.001 (95% CI: 0.0005; 0.0015), P < 0.05). In this group, low RBC folate concentrations (-2SD, 875.4 nmol/l) were associated with a 1.8-day delay (95% CI: 1.7-1.8) in development compared with high concentrations (+2SD, 2119.9 nmol/l). tHcy was negatively associated with embryonic development in the total study population (β = -0.08 (95% CI: -0.14; -0.02), P < 0.01), as well as in the IVF/ICSI subgroup (β = -0.08 (95% CI: -0
Heterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1–7 nights. At 1–6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70–100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2′,3′-dideoxcytidine (ddC or tenofovir largely prevented their EcoHIV/NDK infection by mating (P<0.05 and P<0.003, respectively. In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003 but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.
Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil
Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Nilupa S Gunaratna
Full Text Available Women's nutritional status during conception and early pregnancy can influence maternal and infant outcomes. This study examined the efficacy of pre-pregnancy supplementation with iron and multivitamins to reduce the prevalence of anemia during the periconceptional period among rural Tanzanian women and adolescent girls.A double-blind, randomized controlled trial was conducted in which participants were individually randomized to receive daily oral supplements of folic acid alone, folic acid and iron, or folic acid, iron, and vitamins A, B-complex, C, and E at approximately single recommended dietary allowance (RDA doses for six months.Rural Rufiji District, Tanzania.Non-pregnant women and adolescent girls aged 15-29 years (n = 802.The study arms were comparable in demographic and socioeconomic characteristics, food security, nutritional status, pregnancy history, and compliance with the regimen (p>0.05. In total, 561 participants (70% completed the study and were included in the intention-to-treat analysis. Hemoglobin levels were not different across treatments (median: 11.1 g/dL, Q1-Q3: 10.0-12.4 g/dL, p = 0.65. However, compared with the folic acid arm (28%, there was a significant reduction in the risk of hypochromic microcytic anemia in the folic acid and iron arm (17%, RR: 0.61, 95% CI: 0.42-0.90, p = 0.01 and the folic acid, iron, and multivitamin arm (19%, RR: 0.66, 95% CI: 0.45-0.96, p = 0.03. Inverse probability of treatment weighting (IPTW to adjust for potential selection bias due to loss to follow-up did not materially change these results. The effect of the regimens was not modified by frequency of household meat consumption, baseline underweight status, parity, breastfeeding status, or level of compliance (in all cases, p for interaction>0.2.Daily oral supplementation with iron and folic acid among women and adolescents prior to pregnancy reduces risk of anemia. The potential benefits of supplementation on the risk of
Bülow, Steffen; Kronborg, O
Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a w......Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....
Sezik, M; Aslan, M; Orhan, D D; Erdemoglu, E; Pekcan, M; Mungan, T; Sezik, E
Our aim was to investigate the hypoglycaemic and antioxidant effects of the Helichrysum plicatum ssp. plicatum (HPsP) plant extract in the streptozotocin-induced type 1 diabetes rat model during pregnancy. Five groups (n = 8, each) were formed: (1) diabetic non-mated control, (2) non-diabetic mated control, (3) diabetic mated control, (4) diabetic non-mated treatment and (5) diabetic mated treatment. The HPsP extract was administered orally for 15 days (250 mg/kg body weight), beginning 3 days before mating. The extract led to decreased blood glucose, increased serum insulin, and decreased serum triglycerides in pregnant and non-pregnant diabetic animals. Liver thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) measurements in extract-treated diabetics were similar to non-diabetic pregnant controls, indicating probable reversal of increased lipid peroxidation in the liver. The mean pup number tended to increase (p = 0.06) with extract administration. In conclusion, the beneficial effects we encountered with the periconception use of the studied herbal extract warrant further investigation.
Kwok, Dorothy W S; Boakes, Robert A
This experiment tested whether pre-exposing a taste would reduce its ability to overshadow conditioning to a target taste and whether this effect would depend on the delay between pre-exposure and conditioning. Two groups of rats were pre-exposed to an interfering taste (HCl) either a week before conditioning (Group Distal) or the day preceding conditioning (Group Proximal). In the single conditioning trial, rats were given the target taste (sucrose) and 65min later were injected with lithium. The groups differed as to what they were given to drink 50min after sucrose: The Distal, Proximal and Novel groups were given HCl, while the Control group was given water. Pre-exposure to HCl reduced overshadowing of the sucrose aversion by HCl in Group Proximal but not in Group Distal. Possible explanations for the latter result include extinction of the context-HCl association and loss of context control over an HCl-no outcome association. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available ABSTRACT BACKGROUND: Acupuncture is often used for migraine prophylaxis but its effectiveness is still controversial. This review (along with a companion review on 'Acupuncture for tension-type headache' represents an updated version of a Cochrane review originally published in Issue 1, 2001, of The Cochrane Library. OBJECTIVES: To investigate whether acupuncture is a more effective than no prophylactic treatment/routine care only; b more effective than 'sham' (placebo acupuncture; and c as effective as other interventions in reducing headache frequency in patients with migraine. METHODS: Search methods: The Cochrane Pain, Palliative & Supportive Care Trials Register, CENTRAL, MEDLINE, EMBASE and the Cochrane Complementary Medicine Field Trials Register were searched to January 2008. Selection criteria: We included randomized trials with a post-randomization observation period of at least 8 weeks that compared the clinical effects of an acupuncture intervention with a control (no prophylactic treatment or routine care only, a sham acupuncture intervention or another intervention in patients with migraine. Data collection and analysis: Two reviewers checked eligibility; extracted information on patients, interventions, methods and results; and assessed risk of bias and quality of the acupuncture intervention. Outcomes extracted included response (outcome of primary interest, migraine attacks, migraine days, headache days and analgesic use. Pooled effect size estimates were calculated using a random-effects model. MAIN RESULTS: Twenty-two trials with 4419 participants (mean 201, median 42, range 27 to 1715 met the inclusion criteria. Six trials (including two large trials with 401 and 1715 patients compared acupuncture to no prophylactic treatment or routine care only. After 3 to 4 months patients receiving acupuncture had higher response rates and fewer headaches. The only study with long-term follow up saw no evidence that effects dissipated up
Full Text Available The article presents medical and social aspects of immune prophylaxis of infectious diseases; the history of vaccines and vaccination is presented, as well as perspectives of development of vaccine prophylaxis.
Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography. M Brand, D Bisoz. Abstract. Background. Antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is controversial. We set out to assess the current antibiotic prescribing practice among ...
MacLaughlin, Severence M; Walker, Simon K; Kleemann, David O; Tosh, Darran N; McMillen, I Caroline
Adaptive growth responses of the embryo and fetus to nutritional restraint are important in ensuring early survival, but they are implicated in the programming of hypertension. It has been demonstrated that kidney growth and nephrogenesis are each regulated by intrarenal factors, including the insulin-like growth factors, glucocorticoids, and the renin-angiotensin system. Therefore, we have investigated the impact of periconceptional undernutrition (PCUN; from approximately 6 wk before to 7 days after conception) in singleton (control, n = 18; PCUN, n = 16) and twin pregnancies (control, n = 6; PCUN, n = 5) on the renal mRNA expression of 11beta- hydroxysteroid dehydrogensase type 1 and type 2 (11beta-HSD-1 and -2), the glucocorticoid (GR), and mineralocorticoid receptors, angiotensinogen, angiotensin receptor type 1 (AT1R) and 2 (AT2R), IGF-1 and IGF-2, and IGF1R and IGF2R at approximately 55 days gestation. There was no effect of PCUN or fetal number on fetal weight on relative kidney weight at approximately day 55 of gestation. There was an inverse relationship between the relative weight of the fetal kidney at approximately day 55 and maternal weight loss during the periconceptional period in fetuses exposed to PCUN. Exposure to PCUN resulted in a higher expression of IGF1 in the fetal kidney in singleton and twin pregnancies. Being a twin resulted in higher intrarenal expression of IGF-1 and IGF-2, GR, angiotensinogen, AT1R, and AT2R mRNA at 55 days gestation. Renal 11beta-HSD-2 mRNA expression was higher in PCUN singletons, but not PCUN twins, compared with controls. Thus, there may be an adaptive response in the kidney to the early environment of a twin pregnancy, which precedes the fetal growth restriction that occurs later in pregnancy. The kidney of the twin fetus exposed to periconceptional undernutrition may also be less protected from the consequences of glucocorticoid exposure.
Wijnands, K P J; van Uitert, E M; Roeters van Lennep, J E; Koning, A H J; Mulders, A G M G J; Laven, J S E; Steegers, E A P; Steegers-Theunissen, R P M
Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association? This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies. Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life. In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated. Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses. From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly
Porucznik, Christina A; Cox, Kyley J; Schliep, Karen C; Wilkins, Diana G; Stanford, Joseph B
To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid. Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points. Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data.
McMillen, I Caroline; MacLaughlin, Severence M; Muhlhausler, Beverly S; Gentili, Sheridan; Duffield, Jaime L; Morrison, Janna L
The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of
Koch, J M; Wilmoth, T A; Wilson, M E
Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P brain weights were obtained, as well as left and right ventricular wall thicknesses. On postnatal d 100, a subset of ewe lambs were weighed and challenged with an intravenous injection of GHRH. Lambs from treated ewes had increased (P left ventricular wall was thinner (P development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prophylaxis cup. 872.6290 Section 872.6290 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing...
Glaesner, Nadia; Baelum, Jacob; Strobel, Bjarne W.; Jacobsen, Carsten S.
Mineralisation of atrazine in soil has been shown to depend on previous exposure of the herbicide. In this study, 24 Danish soils were collected and screened for potential to mineralise atrazine. Six soils were chosen, because they had never been exposed to atrazine, whereas 18 soils were chosen because of their history of application of atrazine or the related compound terbuthylazine. None of the 24 soils revealed a mineralisation potential of more than 4% of the added atrazine within a 60 day timeframe. In an atrazine adapted French soil, we found 60% mineralisation of atrazine in 30 days. Cattle manure was applied in order to boost the microbial activity, and a 2-3% increase in the atrazine mineralisation was found in some of the temperate soils, while in the highly adapted French soil it caused a 5% reduction. - The study highlights that pre-exposure of soils to triazine herbicides do not result in rapid mineralization in temperate soils.
El-Dawy, H.A.; Aly El-Sayed, S.M.
This study was performed to evaluate the potency of zinc chloride injected subcutaneously (30 mg/kg b.w.) in male albino mice as a radio-protective agent pre exposure to gamma-irradiation. The investigation of the radio-protective role of zinc chloride was accomplished through measuring the levels of sex hormones, and observation of the chromosomal aberrations and sperm-head abnormalities after exposure to gamma-irradiation. The average of abnormal cells with chromosomal aberration and abnormal sperm % on the 7 th and 21 th days were 32% and 40%, and 14% and 22% respectively in mice exposed to radiation alone compared to 12% and 16%, and 5% and 12% respectively in mice treated with zinc chloride pre-irradiation. Treatment of mice with zinc chloride pre-irradiation induced significant amelioration in FSH and LH hormone levels on the 7 th day only of experimentation period, and showed non-significant amelioration in testosterone level
Sager, Tina; Wolfarth, Michael; Keane, Michael; Porter, Dale; Castranova, Vincent; Holian, Andrij
Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical-chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20 min or 5 min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0-80 µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood-gas barrier in the lung.
Brown, Hannah M; Green, Ella S; Tan, Tiffany C Y; Gonzalez, Macarena B; Rumbold, Alice R; Hull, M Louise; Norman, Robert J; Packer, Nicolle H; Robertson, Sarah A; Thompson, Jeremy G
Diabetes has been linked with impaired fertility but the underlying mechanisms are not well defined. Here we use a streptozotocin-induced diabetes mouse model to investigate the cellular and biochemical changes in conceptus and maternal tissues that accompany hyperglycaemia. We report that streptozotocin treatment before conception induces profound intra-cellular protein β-O-glycosylation (O-GlcNAc) in the oviduct and uterine epithelium, prominent in early pregnancy. Diabetic mice have impaired blastocyst development and reduced embryo implantation rates, and delayed mid-gestation growth and development. Peri-conception changes are accompanied by increased expression of pro-inflammatory cytokine Trail, and a trend towards increased Il1a, Tnf and Ifng in the uterus, and changes in local T-cell dynamics that skew the adaptive immune response to pregnancy, resulting in 60% fewer anti-inflammatory regulatory T-cells within the uterus-draining lymph nodes. Activation of the heat shock chaperones, a mechanism for stress deflection, was evident in the reproductive tract. Additionally, we show that the embryo exhibits elevated hyper-O-GlcNAcylation of both cytoplasmic and nuclear proteins, associated with activation of DNA damage (ɣH2AX) pathways. These results advance understanding of the impact of peri-conception diabetes, and provide a foundation for designing interventions to support healthy conception without propagation of disease legacy to offspring.
Bodnar, Lisa M; Olsen, Jorn; Olsen, Sjurdur; Nohr, Ellen A
Background: The intake of periconceptional multivitamins may decrease the risk of preterm births (PTBs) or small-for-gestational-age (SGA) births. Objective: We related the timing and frequency of periconceptional multivitamin use to SGA births and PTBs and its clinical presentations (ie, preterm labor, premature rupture of membranes, and medical induction). Design: Women in the Danish National Birth Cohort (n = 35,897) reported the number of weeks of multivitamin use during a 12-wk periconceptional period. Cox regression was used to estimate the relation between any multivitamin use and PTBs (2 SDs below the mean on the basis of fetal growth curves). The timing (preconception and postconception) and frequency of use were also analyzed. Regular users (4–6 wk) and partial users (1–3 wk) in each period were compared with nonusers. Results: The association between periconceptional multivitamin use and PTBs varied according to prepregnancy overweight status (P-interaction = 0.07). Regular preconception and postconception multivitamin use in women with a prepregnancy BMI (in kg/m2) PTBs in nonoverweight women. PMID:21795441
Liu, Min; Chen, Jing; Liu, Jue; Zhang, Shikun; Wang, Qiaomei; Shen, Haiping; Zhang, Yiping
To assess socioeconomic inequality in periconceptional folic acid supplementation in China. We used data of periconceptional folic acid (FA) supplementation of rural Chinese women from the National Free Preconception Health Examination Project from 2010 to 2012 and socioeconomic level data from the National Bureau of Statistics. We used logistic models to assess the associations between the prevalence of taking FA and the sociodemographic characteristics of the participants, the couples, and the socioeconomic levels of their region of residence. Of the 907,720 included women, 682,315 (75.62%) of the women reported taking FA. The prevalence of FA supplementation was significantly higher in participants aged 21-29 (75.87%) than in those women aged 40-49 (68.44%, p < 0.01). The prevalence of FA supplementation was significantly higher in the region with the highest Per Capita Gross Regional Product than in the regions with lower Per Capita Gross Regional Product (aOR = 12.20 [95% CI:9.54-15.61]). The higher the per capita net income of farmer households in the region, the higher the prevalence of FA supplementation (aOR = 1.95 [95% CI:1.74-2.18]). The rate of periconceptional FA supplementation among rural Chinese women has increased with the support of China's Health System Reform policy. However, socioeconomic disparities in periconceptional folic acid supplementation remain.
Robert D Herbert
Full Text Available Prophylactic injections of factor VIII reduce the incidence of bleeds and slow the development of joint damage in people with hemophilia. The aim of this study was to identify optimal person-specific prophylaxis regimens for children with hemophilia A.Analytic and numerical methods were used to identify prophylaxis regimens which maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds.It was demonstrated analytically that, for any injection schedule, the regimen that maximizes the lowest factor VIII concentration involves sharing doses between injections so that all of the trough concentrations in a prophylaxis cycle are equal. Numerical methods were used to identify optimal prophylaxis schedules and explore the trade-offs between efficacy and acceptability of different prophylaxis regimens. The prophylaxis regimen which minimizes risk of bleeds depends on the person's pattern of physical activity and may differ greatly from prophylaxis regimens that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize risk of bleeds also differ from prophylaxis regimens that are typically prescribed. Predictions about which regimen is optimal are sensitive to estimates of the effects on risk of bleeds of factor VIII concentration and physical activity.The methods described here can be used to identify optimal, person-specific prophylaxis regimens for children with hemophilia A.
Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M
Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.
Klein, Shannon G.; Pitt, Kylie A.; Carroll, Anthony R.
Researchers have investigated the immediate effects of end-of-century climate change scenarios on many marine species, yet it remains unclear whether we can reliably predict how marine species may respond to future conditions because biota may become either more or less resistant over time. Here, we examined the role of pre-exposure to elevated temperature and reduced pH in mitigating the potential negative effects of future ocean conditions on polyps of a dangerous Irukandji jellyfish Alatina alata. We pre-exposed polyps to elevated temperature (28 °C) and reduced pH (7.6), in a full factorial experiment that ran for 14 d. We secondarily exposed original polyps and their daughter polyps to either current (pH 8.0, 25 °C) or future conditions (pH 7.6, 28 °C) for a further 34 d to assess potential phenotypic plastic responses and whether asexual offspring could benefit from parental pre-exposure. Polyp fitness was characterised as asexual reproduction, respiration, feeding, and protein concentrations. Pre-exposure to elevated temperature alone partially mitigated the negative effects of future conditions on polyp fitness, while pre-exposure to reduced pH in isolation completely mitigated the negative effects of future conditions on polyp fitness. Pre-exposure to the dual stressors, however, reduced fitness under future conditions relative to those in the control treatment. Under future conditions, polyps had higher respiration rates regardless of the conditions they were pre-exposed to, suggesting that metabolic rates will be higher under future conditions. Parent and daughter polyps responded similarly to the various treatments tested, demonstrating that parental pre-exposure did not confer any benefit to asexual offspring under future conditions. Importantly, we demonstrate that while pre-exposure to the stressors individually may allow Irukandji polyps to acclimate over short timescales, the stressors are unlikely to occur in isolation in the long term, and
Klein, Shannon G.
Researchers have investigated the immediate effects of end-of-century climate change scenarios on many marine species, yet it remains unclear whether we can reliably predict how marine species may respond to future conditions because biota may become either more or less resistant over time. Here, we examined the role of pre-exposure to elevated temperature and reduced pH in mitigating the potential negative effects of future ocean conditions on polyps of a dangerous Irukandji jellyfish Alatina alata. We pre-exposed polyps to elevated temperature (28 °C) and reduced pH (7.6), in a full factorial experiment that ran for 14 d. We secondarily exposed original polyps and their daughter polyps to either current (pH 8.0, 25 °C) or future conditions (pH 7.6, 28 °C) for a further 34 d to assess potential phenotypic plastic responses and whether asexual offspring could benefit from parental pre-exposure. Polyp fitness was characterised as asexual reproduction, respiration, feeding, and protein concentrations. Pre-exposure to elevated temperature alone partially mitigated the negative effects of future conditions on polyp fitness, while pre-exposure to reduced pH in isolation completely mitigated the negative effects of future conditions on polyp fitness. Pre-exposure to the dual stressors, however, reduced fitness under future conditions relative to those in the control treatment. Under future conditions, polyps had higher respiration rates regardless of the conditions they were pre-exposed to, suggesting that metabolic rates will be higher under future conditions. Parent and daughter polyps responded similarly to the various treatments tested, demonstrating that parental pre-exposure did not confer any benefit to asexual offspring under future conditions. Importantly, we demonstrate that while pre-exposure to the stressors individually may allow Irukandji polyps to acclimate over short timescales, the stressors are unlikely to occur in isolation in the long term, and
Klein, Shannon G.; Pitt, Kylie A.; Carroll, Anthony R.
Researchers have investigated the immediate effects of end-of-century climate change scenarios on many marine species, yet it remains unclear whether we can reliably predict how marine species may respond to future conditions because biota may become either more or less resistant over time. Here, we examined the role of pre-exposure to elevated temperature and reduced pH in mitigating the potential negative effects of future ocean conditions on polyps of a dangerous Irukandji jellyfish Alatina alata. We pre-exposed polyps to elevated temperature (28 °C) and reduced pH (7.6), in a full factorial experiment that ran for 14 d. We secondarily exposed original polyps and their daughter polyps to either current (pH 8.0, 25 °C) or future conditions (pH 7.6, 28 °C) for a further 34 d to assess potential phenotypic plastic responses and whether asexual offspring could benefit from parental pre-exposure. Polyp fitness was characterised as asexual reproduction, respiration, feeding, and protein concentrations. Pre-exposure to elevated temperature alone partially mitigated the negative effects of future conditions on polyp fitness, while pre-exposure to reduced pH in isolation completely mitigated the negative effects of future conditions on polyp fitness. Pre-exposure to the dual stressors, however, reduced fitness under future conditions relative to those in the control treatment. Under future conditions, polyps had higher respiration rates regardless of the conditions they were pre-exposed to, suggesting that metabolic rates will be higher under future conditions. Parent and daughter polyps responded similarly to the various treatments tested, demonstrating that parental pre-exposure did not confer any benefit to asexual offspring under future conditions. Importantly, we demonstrate that while pre-exposure to the stressors individually may allow Irukandji polyps to acclimate over short timescales, the stressors are unlikely to occur in isolation in the long term, and
BACKGROUND: Neural tube defects (NTDs) are severe abnormalities of the central nervous system that occur as a result of abnormal development in the third and fourth weeks of gestation. Studies have shown that periconceptional folic acid (FA) can reduce both the incidence and recurrence of NTDs. METHODS: A cohort study was carried out using the electronic hospital booking records of women delivering in a large Dublin maternity hospital between 2000 and 2007. Logistic regression analyses were performed to measure the associations between maternal factors and optimal FA use. RESULTS: Of the 61,252 women in the cohort, 85% reported taking FA at some point during the periconceptional period; however, only 28% took FA as recommended. Factors associated with taking the recommended amount of FA included nulliparity [adjusted OR: 1.35 (95% CI: 1.28-1.43)], early booking (<12 weeks) [OR: 1.24 (95% CI: 1.17-1.31)], increasing maternal age (e.g. 30-34 years) [OR: 1.39 (95% CI: 1.30-1.48)], private health care [OR: 4.32 (95% CI: 4.1-4.6)] and fertility treatment [OR: 2.88 (95% CI: 2.44-3.40)]. Factors associated with taking less than recommended or no FA included unplanned pregnancy [OR: 0.08 (0.07-0.08)], lower socio-economic status (e.g. unemployed) [OR: 0.63 (95% CI: 0.55-0.71)], non-Irish nationality [OR: 0.82 (0.74-0.90)] and smokers [OR: 0.51 (95% CI: 0.47-0.55)]. CONCLUSIONS: Social, demographic and economic factors have an important influence on the FA uptake. Vulnerable groups who report limited uptake of FA need to be specifically targeted in future Public Health campaigns and further consideration needs to be given to the debate on food fortification in countries where this is currently not available.
Britni M Brown
Full Text Available Heat stress at the time of conception affects the subsequent milk production of primiparous Holstein cows; however, it is unknown whether these effects are maintained across multiple lactations. Therefore, the objective of the current study was to examine the relationship between periconceptional heat stress and measurements of milk production and composition in cows retained within a herd for multiple lactations. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included milk production data and milk composition data from over 75,000 and 44,000 Holstein cows, respectively, born between 2000 and 2010 in Florida, Georgia, and Texas. Conception dates were calculated by subtracting 276 d from the recorded birth date. Records for cows conceived within the months of June, July, and August were retained as heat stress conceived (HSC cows; cows conceived within the months of December, January, and February were retained as thermoneutral conceived (TNC contemporaries. Adjusted 305-d mature equivalent milk, protein percent and fat percent were evaluated with a mixed model ANOVA using SAS. Milk production was significantly affected by periconceptional heat stress. When a significant difference or tendency for a difference was detected between the HSC and TNC cows, the TNC produced more milk in all but one comparison. The advantage in milk production for the TNC cows over the HSC cows ranged from 82 ± 42 to 399 ± 61 kg per lactation. Alterations in fat and protein percentage were variable and most often detected in first lactations (first > second or third. Overall, the most striking result of this study is the consistency of the relationship between HSC and milk production. The nature of this relationship suggests that heat stress at or around the time of conception impairs cow milk yield throughout her lifetime.
Reid, James M; Jacklin, Derek L; Winters, Boyer D
The neural mechanisms and brain circuitry involved in the formation, storage, and utilization of multisensory object representations are poorly understood. We have recently introduced a crossmodal object recognition (CMOR) task that enables the study of such questions in rats. Our previous research has indicated that the perirhinal and posterior parietal cortices functionally interact to mediate spontaneous (tactile-to-visual) CMOR performance in rats; however, it remains to be seen whether other brain regions, particularly those receiving polymodal sensory inputs, contribute to this cognitive function. In the current study, we assessed the potential contribution of one such polymodal region, the hippocampus (HPC), to crossmodal object recognition memory. Rats with bilateral excitotoxic HPC lesions were tested in two versions of crossmodal object recognition: (1) the original CMOR task, which requires rats to compare between a stored tactile object representation and visually-presented objects to discriminate the novel and familiar stimuli; and (2) a novel 'multimodal pre-exposure' version of the CMOR task (PE/CMOR), in which simultaneous exploration of the tactile and visual sensory features of an object 24 h prior to the sample phase enhances CMOR performance across longer retention delays. Hippocampus-lesioned rats performed normally on both crossmodal object recognition tasks, but were impaired on a radial arm maze test of spatial memory, demonstrating the functional effectiveness of the lesions. These results strongly suggest that the HPC, despite its polymodal anatomical connections, is not critically involved in tactile-to-visual crossmodal object recognition memory. Copyright © 2012 Elsevier Inc. All rights reserved.
Souza, Silvia R.; Blande, James D.; Holopainen, Jarmo K.
The roles that ozone and nitric oxide (NO), the chief O 3 precursor, play in the antioxidative balance and inducible volatile emissions of lima bean were assessed. Exposure to O 3 inhibited APX, CAT, and GR, decreased GSH content and induced emissions of (E)-β-ocimene, limonene, 1,8-cineole, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene (E)-DMNT, 2-butanone and nonanal. O 3 did not induce emissions of (E)-β-caryophyllene and appeared to reduce the antioxidative capacity of plants to a greater extent than NO and NO followed by O 3 (NO/O 3 ) treatments. There were significant differences in emissions of (E)-β-ocimene and linalool between NO/O 3 treated plants and controls, but no differences in antioxidant concentrations. A model to explain the relationships between the ascorbate–glutathione cycle and O 3 and NO inducible volatiles was proposed. Our findings suggest that prior exposure to NO modulates the oxidative effect of ozone by the process of cross-tolerance, which might regulate the antioxidative system and induction of volatile organic compounds. -- Highlights: •NO and O 3 disturb antioxidant defenses and cause lipid peroxidation in lima bean plants. •Exposure to NO before exposure to O 3 does not alter the antioxidant defenses and malondialdehyde levels. •The total sum of induced volatiles is reduced in plants that are exposed to NO and then O 3 . •The antioxidant system and induced VOC emission were balanced by pre-exposure to NO before O 3 . -- Capsule: Nitric oxide modulates the ozone-induced oxidative stress in lima bean by cross-tolerance effect
Peake, Jordana N; Copp, Andrew J; Shawe, Jill
It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.
Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori
Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (Phemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).
Iodine is a highly volatile element therefore being very mobile in the environment. It enters the metabolism of living organisms and is selectively taken up and concentrated in the thyroid gland. The plume (cloud-like formation) of radioactive material that might be released in the environment in the case of a serious nuclear accident, primarily consists of the radioactive isotopes of iodine. Among those, due to its decay properties, is the most important 131 I. The effective means of protecting the thyroid gland against exposure to radioactive iodine is an intake of stable iodine. Therefore, one of the central issues in the emergency planning is to determine whether and at which projected thyroid radiation dose stable iodine should be given to the population. The International Atomic Energy Agency (IAEA) set the generic optimized intervention value for iodine prophylaxis to 100 mGy of avertable committed dose to a thyroid.The prophylaxis is implemented by utilizing the pills of pills of potassium iodine (KI). The efficacy of KI in protecting the thyroid gland depends upon the time of intake relative to the start of exposure to radioactive iodine. The best results are obtained if KI is taken 1-2 hours before or immediately after the start of exposure. The recommended dosage, based upon the study performed by Il'in et.al. is 130 mg/day. KI should be taken at least three days after the acute exposure to radioiodine, to prevent accumulation in a thyroid gland of radioiodine excreted from the other compartments of the body. The largest epidemiological study on the effects of KI prophylaxis ever performed was the one in Poland after the Chernobyl accident. Stable iodine was given as single dose of KI solution to 10.5 million of children and 7 millions of adults. Among children no serious side effects were seen while only two adults (with previously recorded iodine sensitivity) had severe respiratory distresses. Polish experiences showed that rapid response to such
Full Text Available BACKGROUNDS: The etiology of congenital heart defect (CHD is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese population. METHODS: An age and gender matched case-control study with standardized data collection involving 201 pairs was conducted. Periconceptional toxicants exposure was obtained through a structured questionnaire. A job exposure matrix (JEM was used for toxicants exposure assessment. Genotyping of the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of the ABCB1 gene C3435T polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and umbilical cords were collected to investigate the impact of C3435T polymorphism on the transcription and translation activities of ABCB1 gene. RESULTS: MATERNAL PERICONCEPTIONAL EXPOSURES TO PHTHALATES (ADJUSTED OR: 1.6; 95%CI: 1.0-2.6 and alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1-3.0 were associated with a higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT genotypes (OR: 2.0, 95%CI: 1.1-3.5, P-value: 0.021. Children carrying the CC/CT genotype and periconceptionally exposed to phthalates and alkylphenolic compounds suffered almost 3.5-fold increased risk of having CHD than non-exposed children with TT genotype (adjusted OR: 3.5, 95%CI: 1.5-7.9, P-value: 0.003, and the OR changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8-10.9,P-value:0.001. The ABCB1 mRNA expression of the TT genotype was significantly higher than that of the CC genotype (P = 0.03. Compared with TT genotype, lower P-glycoprotein expression was observed for the CC/CT genotypes. CONCLUSION: The C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a Han Chinese
ABSTRACT. Background: There are no local guidelines for prophylaxis against Venous Thrombo-Embolism (VTE). .... of leg ulceration in the age matched general population. (9.6% to ... number of deaths and its cause amongst these patients.
In this podcast, Dr. David Swerdlow discusses prophylaxis after exposure to Coxiella burnetii. It is important to know who should be treated and how they should be treated after an intentional release with possible bioterrorism agents, including Coxiella burnetii.
Nielsen, Lea Juul; Matzen, Steen H
BACKGROUND: Venous thromboembolism is a well-documented complication of surgery, including plastic surgery. However, few consensus guidelines on thromboembolism prophylaxis exist in plastic surgery and, thus, the different approaches in the public as well as the private clinics in Denmark were...... investigated using a web-based survey. METHODS: Forty-two clinics were contacted and 45% responded. RESULTS: The collected data reveals a lack of consensus in plastic surgery in Denmark, not only regarding the use of mechanical and chemical prophylaxis, but also which type of prophylaxis to apply, the duration...... of prophylaxis, and how to risk stratify the patients. CONCLUSION: The development of a guideline, based on plastic surgical data, using a validated risk assessment model, which combines the surgical risk with the patient related risk and recommends guidelines for mechanical as well as chemoprophylaxis...
Stevens, Adam; Begum, Ghazala; Cook, Alice; Connor, Kristin; Rumball, Christopher; Oliver, Mark; Challis, John; Bloomfield, Frank; White, Anne
Maternal food restriction is associated with the development of obesity in offspring. This study examined how maternal undernutrition in sheep affects the fetal hypothalamic glucocorticoid receptor (GR) and the appetite-regulating neuropeptides, proopiomelanocortin (POMC) and neuropeptide Y, which it regulates. In fetuses from ewes undernourished from -60 to +30 d around conception, there was increased histone H3K9 acetylation (1.63-fold) and marked hypomethylation (62% decrease) of the POMC gene promoter but no change in POMC expression. In the same group, acetylation of histone H3K9 associated with the hypothalamic GR gene was increased 1.60-fold and the GR promoter region was hypomethylated (53% decrease). In addition, there was a 4.7-fold increase in hypothalamic GR expression but no change in methylation of GR gene expression in the anterior pituitary or hippocampus. Interestingly, hypomethylation of both POMC and GR promoter markers in fetal hypothalami was also identified after maternal undernutrition from -60 to 0 d and -2 to +30 d. In comparison, the Oct4 gene, was hypermethylated in both control and underfed groups. Periconceptional undernutrition is therefore associated with marked epigenetic changes in hypothalamic genes. Increase in GR expression in the undernourished group may contribute to fetal programming of a predisposition to obesity, via altered GR regulation of POMC and neuropeptide Y. These epigenetic changes in GR and POMC in the hypothalamus may also predispose the offspring to altered regulation of food intake, energy expenditure, and glucose homeostasis later in life.
van Schalkwyk, Julie; Van Eyk, Nancy
To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June 2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. SUMMARY STATEMENTS: 1. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following operative vaginal delivery. (II-1) 2. There is insufficient evidence to argue for or against the use of prophylactic antibiotics to reduce infectious morbidity for manual removal of the placenta. (III) 3. There is insufficient evidence to argue for or against the use of
Full Text Available BACKGROUND: Extremely low frequency (ELF magnetic fields (MF are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells. METHODOLOGY/PRINCIPAL FINDINGS: Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS. Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone. CONCLUSIONS: The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.
Luukkonen, Jukka; Liimatainen, Anu; Höytö, Anne; Juutilainen, Jukka; Naarala, Jonne
Extremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells. Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone. The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.
Dolan, Samantha B.; Sotir, Mark J.; Han, Pauline; Blanton, Jesse D.; Rao, Sowmya R.; LaRocque, Regina C.; Ryan, Edward T.
strength of the vaccine recommendation at the destination country, duration of stay, availability of postexposure prophylaxis, potential for exposure to animals, and likelihood of recurrent travel to high-risk destinations. PMID:24359420
Dolan, Samantha B; Jentes, Emily S; Sotir, Mark J; Han, Pauline; Blanton, Jesse D; Rao, Sowmya R; LaRocque, Regina C; Ryan, Edward T; Abraham, George M; Alvarez, Salvador; Ansdell, Vernon; Yates, Johnnie A; Atkins, Elisha H; Cahill, John; Birich, Holly K; Vitek, Dagmar; Connor, Bradley A; Dismukes, Roberta; Kozarsky, Phyllis; Dosunmu, Rone; Goad, Jeffrey A; Hagmann, Stefan; Hale, DeVon; Hynes, Noreen A; Jacquerioz, Frederique; McLellan, Susan; Knouse, Mark; Lee, Jennifer; LaRocque, Regina C; Ryan, Edward T; Oladele, Alawode; Demeke, Hanna; Pasinski, Roger; Wheeler, Amy E; Rao, Sowmya R; Rosen, Jessica; Schwartz, Brian S; Stauffer, William; Walker, Patricia; Vinetz, Joseph
of stay, availability of postexposure prophylaxis, potential for exposure to animals, and likelihood of recurrent travel to high-risk destinations.
Schrijvers, L H; Kars, M C; Beijlevelt-van der Zande, M; Peters, M; Schuurmans, M J; Fischer, K
Given the lifelong therapy in haemophilia patients, insight in non-adherence behaviour from a patient perspective is important to understand patients' difficulties with the following treatment recommendations. The aim of this study was to clarify the process underlying adherence (behaviour) to prophylactic treatment, from a patients' perspective. To develop a grounded theory, a qualitative study using individual in-depth interviews was performed to understand experiences, perceptions and beliefs concerning adherence to prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using prophylaxis were interviewed. Patients were asked how they experience their task to administer prophylaxis and how they adhere to this. The interviews were transcribed, coded and analysed in an iterative process, leading to the development of the grounded theory. Adherence was determined by the position of prophylaxis in life. The position of prophylaxis was determined by the perception of prophylaxis and the ability to exert prophylaxis. Patients' perception was influenced by two main factors: acceptance of haemophilia and feeling/fearing symptoms. The ability to exert prophylaxis was influenced by understanding haemophilia and prophylaxis and planning/infusion skills. The combination of different perceptions and skills led to four main positions of prophylaxis in life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors' advice, struggling with irregular situations, (iii) prophylaxis is too much to handle, (iv) prophylaxis is a confrontation with illness. The adherence level gradually decreased from position 1 to 4. This information can be used to design tailored interventions to promote adherence. © 2015 John Wiley & Sons Ltd.
Whitlock, G; McCormack, C; Fearnley, J; McOwan, A
There are limited outcome data for men who have sex with men (MSM) who have received HIV postexposure prophylaxis (PEP). The objective of this service evaluation was to determine HIV incidence and repeat PEP use among MSM PEP recipients in London, UK. Retrospective electronic case-note review of all MSM who were prescribed PEP between January and April 2013 at a central London sexual health service. 530 MSM received PEP between 1 January and 30 June 2013. Of these, 449 had more than 30 days subsequent follow-up at our service. Median age was 31 years. PEP indication was unprotected anal intercourse, 98% (receptive 88% and insertive 10%) and other, 2%. Up to 1 November 2015, total follow-up was 756 person-years. 183 users received repeat PEP. The total number of repeat PEP courses was 442. 57 MSM newly acquired HIV: the HIV incidence was 7.6 per 100 person-years. PEP was associated with a high risk of subsequent HIV seroconversion in this cohort; this group may be appropriate candidates for pre-exposure prophylaxis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Fahey Tom P
Full Text Available Abstract Background Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption. Methods A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week, moderate (6-20 units per week and high (>20 units per week. Results Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80, Irish nationality OR 16.5 (95% CI 14.9 to 18.3, private health care OR 5.83 (95% CI 5.38 to 6.31 and smoking OR 1.86 (95% CI 1.73 to 2.01. Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91 and illicit drug use OR 6.46 (95% CI 3.32 to 12.60. High consumption was associated with very preterm birth ( Conclusions Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.
Abstract Background Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption. Methods A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week). Results Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups. Conclusions Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.
Gomes, Sandra; Lopes, Carla; Pinto, Elisabete
To summarize the recommendations on folate intake and folic acid supplementation and fortification in the periconceptional period, aimed at prevention of neural tube defects (NTD), provided by official health organizations in different countries worldwide and WHO. Information on recommendations for folate and folic acid intake in the periconceptional period was gathered from the websites of official national health organizations of several countries worldwide and from the WHO website. WHO, selected developed countries and emerging economies, totalling thirty-six countries worldwide (some European, BRICS, G8, Asian Tiger/Asian Dragon and Australia). Recommendations differ between countries, although the majority (69·4 %) recommend a healthy diet plus a folic acid supplement of 400 µg/d from preconception (4-12 weeks) until the end of the first trimester of pregnancy (8-12 weeks). The same recommendation is issued by the WHO. Dosages for women at high risk of NTD are up to 4-5 mg/d (for 41·7 % of studied countries). The recommended intake for folate is in the range of 300-400 µg/d for women of childbearing age and 500-600 µg/d for pregnant women in different countries and WHO. Five countries emphasize the importance of a healthy diet rendering supplementation needless. By contrast, five others advise a healthy diet and supplementation plus mandatory fortification. Only one mentions the importance of ensuring an adequate folate status and refers to checking with a health-care provider on the need for supplements. Different recommendations regarding folate and folic acid, seeking NTD prevention, are available worldwide; however, most countries and WHO focus on a healthy diet and folic acid supplementation of 400 µg/d periconceptionally.
Palich, Romain; Martin-Blondel, Guillaume; Cuzin, Lise; Le Talec, Jean-Yves; Boyer, Pierre; Massip, Patrice; Delobel, Pierre
HIV postexposure prophylaxis (PEP) is indicated after sexual exposure with high risk of transmission. Men who have sex with men (MSM) are the main target of PEP. The aim of our study was to investigate the experience and shortcomings of PEP among people with a high risk of HIV exposure. Subjects with ongoing follow-up for HIV infection and PEP history were selected for the qualitative study. Semistructured interviews were conducted at the patients' homes. They were audio-recorded, transcribed and deidentified before data analysis, double coding and thematic analysis with an inductive approach. Twenty-three patients were eligible for the qualitative study. Thirteen interviews were carried out. All patients were 20-60-year-old MSM. The median time between PEP and HIV diagnosis was 3.3 years (interquartile range (IQR) 25-75 =0.9-4.9). Many participants reported negative PEP experiences: awkward access to the PEP clinic, uneasiness and shame in the hospital setting, unpleasant interaction and moral disapprobation from the medical staff, treatment intolerance and prevention messages that were 'inconsistent with real life' CONCLUSION: Our data highlight PEP management failures among its target population that may have compromised any subsequent attempts to seek out PEP. Practitioners should be more aware of MSM sexual contexts and practices. PEP consultations should provide the opportunity to discuss prevention strategies with highly exposed HIV-negative subjects, which may include pre-exposure prophylaxis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Full Text Available Obesity has become a severe worldwide problem. Compared to healthy-weight individuals, obese individuals seem to show an increased sensitivity to tempting food. In the present study, we test the pre-exposure effect, which implies that consumption of tempting food is decreased after exposure to tempting food cues in a context of a task that discourages food consumption. Healthy-weight and obese-weight participants were recruited via social media and university channels. Participants took part in a scrabble task with either candy letters or foam letters and subsequently engaged in a taste test. Results showed that in healthy-weight participants, consumption was reduced after solving the scrabble task with candy letters in comparison to foam letters. In obese-weight participants, consumption was reduced in the condition using foam letters (in comparison with healthy-weight participants. The pre-exposure effect was replicated in healthy-weight participants, but could not be observed in participants with obesity, since consumption was reduced in general in this group. Our results suggest that more work should be done to understand how food nudges work in the context of obesity.
Jensen, Dorte M; Korsholm, Lars; Ovesen, Per
Objectives : To study the association between peri-conceptional HbA1c and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). Methods: Prospective data collection in 933 singleton pregnancies complicated by type 1 diabetes. Results: The risk of serious adverse ou...... malformation rate increased significantly at HbA1c above 10.4% whereas perinatal mortality was increased even at Hba1c below 6.9%. Conclusions: These results support recent guidelines of pre-conceptional HbA1c levels below 7% in women with type 1 diabetes....
McGowan, Ian; Dezzutti, Charlene S; Siegel, Aaron; Engstrom, Jarret; Nikiforov, Alexiy; Duffill, Kathryn; Shetler, Cory; Richardson-Harman, Nicola; Abebe, Kaleab; Back, David; Else, Laura; Egan, Deidre; Khoo, Saye; Egan, James E; Stall, Ronald; Williams, Peter E; Rehman, Khaleel K; Adler, Amy; Brand, Rhonda M; Chen, Beatrice; Achilles, Sharon; Cranston, Ross D
Long-acting injectable antiretroviral agents are being developed for HIV-1 prevention. The MWRI-01 study was done to characterise the safety, acceptability, and pharmacokinetic and pharmacodynamic profile of long-acting rilpivirine. We did a phase 1 open-label study at the University of Pittsburgh. We enrolled healthy individuals (aged 18-45 years) who were seronegative for HIV-1. Participants were assigned alternately one intramuscular dose of either 1200 mg or 600 mg long-acting rilpivirine, beginning with the 1200 mg dose. We obtained plasma specimens, genital and rectal fluids, and tissue samples (rectal, cervical, and vaginal) before and after exposure to long-acting rilpivirine for assessment of pharmacokinetics and ex-vivo biopsy challenge with HIV-1. Our primary objective was to characterise product safety, and the analysis included all enrolled participants. This trial is registered with ClinicalTrials.gov, number NCT01656018. 36 participants were enrolled into the study, of whom 24 were women and 12 men. 12 women and six men received each dose. 204 adverse events were reported among the 36 participants, of which 200 (98%) were grade 1-2. The most common adverse event was injection site reaction. All grade 3 and 4 adverse events were deemed not related to rilpivirine. Geometric mean (90% CI) concentrations in plasma of rilpivirine at day 28 post dose were 53 ng/mL (38-67) in women and 43 ng/mL (23-63) in men for the 1200 mg dose and 28 ng/mL (19-37) in women and 17 ng/mL (9-24) in men for the 600 mg dose. The tissue-to-plasma ratio for rilpivirine in rectal tissue was about two-fold higher than in vaginal and cervical tissue (1·10-1·53 vs 0·61-0·72 and 0·50-0·71, respectively). Exposure to long-acting rilpivirine suppressed viral replication significantly in rectal tissue (psuppression persisted for up to 4 months. By contrast, no viral suppression was seen in cervical or vaginal tissue. Ongoing research will characterise longer term safety and acceptability of multiple injections and help ascertain whether long-acting rilpivirine should advance to assessment of efficacy in preventing HIV-1 infection. Bill & Melinda Gates Foundation. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Calabrese, Sarah K; Earnshaw, Valerie A; Krakower, Douglas S; Underhill, Kristen; Vincent, Wilson; Magnus, Manya; Hansen, Nathan B; Kershaw, Trace S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F
Social biases among healthcare providers could limit PrEP access. In this survey study of 115 US medical students, we examined associations between biases (racism and heterosexism) and PrEP clinical decision-making and explored prior PrEP education as a potential buffer. After viewing a vignette about a PrEP-seeking MSM patient, participants reported anticipated patient behavior (condomless sex, extra-relational sex, and adherence), intention to prescribe PrEP to the patient, biases, and background characteristics. Minimal evidence for racism affecting clinical decision-making emerged. In unadjusted analyses, heterosexism indirectly affected prescribing intention via all anticipated behaviors, tested as parallel mediators. Participants expressing greater heterosexism more strongly anticipated increased risk behavior and adherence problems, which were associated with lower prescribing intention. The indirect effect via condomless sex remained significant adjusting for background characteristics. Prior PrEP education did not buffer any indirect effects. Heterosexism may compromise PrEP provision to MSM and should be addressed in PrEP-related medical education.
Underhill, Kristen; Morrow, Kathleen M; Colleran, Christopher; Calabrese, Sarah K; Operario, Don; Salovey, Peter; Mayer, Kenneth H
We investigated message comprehension and message framing preferences for communicating about PrEP efficacy with US MSM. We conducted eight focus groups (n = 38) and n = 56 individual interviews with MSM in Providence, RI. Facilitators probed comprehension, credibility, and acceptability of efficacy messages, including percentages, non-numerical paraphrases, efficacy ranges versus point estimates, and success- versus failure-framed messages. Our findings indicated a range of comprehension and operational understandings of efficacy messages. Participants tended to prefer percentage-based and success-framed messages, although preferences varied for communicating about efficacy using a single percentage versus a range. Participants reported uncertainty about how to interpret numerical estimates, and many questioned whether trial results would predict personal effectiveness. These results suggest that providers and researchers implementing PrEP may face challenges in communicating with users about efficacy. Efforts to educate MSM about PrEP should incorporate percentage-based information, and message framing decisions may influence message credibility and overall PrEP acceptability.
Carballo-Diéguez, Alex; Balán, Ivan C; Brown, William; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Marzinke, Mark A; Hendrix, Craig W; Piper, Jeanna M; Richardson, Barbra A; Grossman, Cynthia; Johnson, Sherri; Gomez, Kailazarid; Horn, Stephanie; Kunjara Na Ayudhya, Ratiya Pamela; Patterson, Karen; Jacobson, Cindy; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen; Lama, Javier; McGowan, Ian; Cranston, Ross D
Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.
Full Text Available Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1 daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, 2 daily use of reduced-glycerin 1% tenofovir (RG-TFV gel applied rectally, and 3 RG-TFV gel applied before and after receptive anal intercourse (RAI-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187 were men who have sex with men and transgender women enrolled in the United States (42%, Thailand (29%, Peru (19% and South Africa (10%. Mean age was 31.4 years (range 18-64 years. Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.
Kari S Anderson
Full Text Available Kari S Anderson, Victoria M Mullally, Linda M Fredrick, Andrew L CampbellAbbott Laboratories, Abbott Park, IL, USAAbstract: Respiratory syncytial virus (RSV is a significant cause of morbidity in high-risk infants. Palivizumab is proven to prevent serious RSV disease, but compliance with prophylaxis (monthly doses during the RSV season is essential to ensure protection. We invited 453 pediatricians to participate in a survey to identify their perspectives of barriers to compliance and interventions to improve compliance with palivizumab prophylaxis schedules. One hundred physicians from five continents completed the survey, identifying caregiver inconvenience, distance to clinic, cost of prophylaxis, and lack of understanding of the severity of RSV as the most common reasons for noncompliance. They recommended provision of educational materials about RSV, reminders from hospital or clinic, and administration of prophylaxis at home to increase compliance. Globally, physicians recognize several obstacles to prophylaxis compliance. This survey suggests that focused proactive interventions such as empowering caregivers with educational materials and reducing caregiver inconvenience may be instrumental to increase compliance.Keywords: medication adherence, respiratory syncytial virus infections, infant, premature, immunization, passive
Full Text Available During the period of neutropenia due to chemotherapy, patients have high risk of infections. The use of antibiotic prophylaxis to reduce neutropenia-related complications in oncologic patients is still disputed. Recent meta-analysis and clinical trials demonstrated that antibiotic prophylaxis with chinolons reduces fever episodes, bacterial infections and mortality in adult oncologic patients with neutropenia due to chemotherapy for acute leukaemia. In paediatric patients, the only randomized, double-blind, prospective study up till now suggested that Amoxicillin clavulanate may represent an effective prophylactic treatment to reduce fever and infections in oncologic children with neutropenia, with an efficacy statistically demonstrated only in patients with acute leukaemia. Considering the risk of resistances, antibiotic-prophylaxis should be used only in selected patients.
Cole, Catherine H
Venous thromboembolism (VTE) is rare in children and young adolescents, and occurs predominantly in those with congenital heart disease in whom guidelines exist for VTE prophylaxis. For other paediatric patients, the rarity of the event makes writing an evidence-based clinical practice guideline difficult because each of the known risk factors contributes only a small increase in risk. Thrombophilia screening is controversial because few results assist with prediction of likely thrombosis and may not alter recommendations for prophylaxis. Recent publications highlight the importance of non-pharmacological prevention of VTE in children and adolescents undergoing surgery and the importance of liaison among surgeon, anaesthetist and haematologist. This annotation was written with the aim of collating current evidence for VTE prophylaxis and emphasising the need for further research in vulnerable subgroups.
Full Text Available The article is dedicated to the actual problem of modern health care — pneumococcal infections and opportunities of its prophylaxis. Authors describe risk groups of development of invasive pneumococcal infections. A characteristics of available at the present times in Russia and all over the world vaccines, including pneumococcal 7-valent vaccine (PCV7 Prevenar, intended to the prophylaxis of pneumococcal infections in children under the age 2 months — 5 years old. An experience of PCV7 use in the world in analyzed. The article gives an estimation of perspectives of inclusion of PCV7 to the national immunizations schedule.Key words: children, pneumococcal infections, prophylaxis, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:62-69
showing the clear picture about HIV post exposure prophylaxis in the work place were non-existent. ... formal (separate) HIV post-exposure prophylaxis centre with proper guideline was non-existent in ..... related challenges at work and home.
Khanna, Aditya S; Schumm, Phil; Schneider, John A
Young Black men who have sex with men (YBMSM) are the only population in the United States who have experienced rising human immunodeficiency virus incidence over the past decade. Consistent pre-exposure prophylaxis (PrEP) use can substantially reduce the risk of human immunodeficiency virus acquisition. What differentiates those who become aware of PrEP, and those who do not, remains largely unknown. The social networks of YBMSM can impact their awareness of PrEP; to examine this impact, we used two waves of Facebook data from "uConnect"-a longitudinal cohort study of YBMSM in Chicago (n = 266). While PrEP awareness increased from 45% at baseline to 75% at follow-up, its use remained low (4% and 6%). There were 88 PrEP-unaware individuals at baseline who became aware (BA) by follow-up, and 56 who remained persistently unaware. While the persistently unawares had a higher median number of total Facebook friends, the BAs had a higher median numbers of friends who participated in uConnect, who were PrEP-aware, and who practiced behaviors previously found to be associated with individual-level awareness of PrEP at baseline. The BAs also had substantially more "influential" friends. These findings demonstrate the potential of social networks in raising PrEP awareness and use among YBMSM. Copyright © 2016 Elsevier Inc. All rights reserved.
Perez, M.R.; Gisone, P.; Rojo, A.M.; Dubner, D.; Bruno, H.
The indication for the blockade of thyroid gland by the administration of stable iodide is the main countermeasure for diminishing the thyroid uptake of radioiodine following radiological accidents with potential release of radioiodine into the environment in order to avoid deterministic effects and to decrease the probability of stochastic effects. Iodine prophylaxis should be considered along with other countermeasures like sheltering indoors, evacuation and control on contaminated foods. In this communication different factors related to accidental situations regarding iodine prophylaxis are evaluated. A therapeutical scheme is proposed in order to be applied in countries of this region. (author). 4 refs
Sri Widayati; Tedjasari, R. S.; Elfida
Study of iodine prophylaxis following nuclear accidents has been done. Giving stable iodine to a population exposed by I-131 is one of preventive action from internal radiation to the thyroid gland. Stable iodine could be given as Kl tablet in a range of dose of 30 mg/day to 130 mg/day. Improper giving of stable iodine could cause side effect to health, so then some factors should be considered i. e. dose estimation, age, dose of stable iodine to be given, duration of stable iodine prophylaxis and risk of health. (author)
Aly, S.M.; Eldawy, H.A.E.; Ragab, E.A.
The present study was prepared to evaluate the potency of methoxy dimethylamino phenyl epiandrosterone (an anabolic agent animal in origin with an additive side chain) in a dose of 35 μ/g/kg b.wt in male albino mice as a radio-protective agent pre-exposure to gamma irradiation. This was accomplished through measuring follicular stimulating hormone (FSH), luteinizing hormone (LH) and prostaglandin-E 2 (PGE 2 ) and endothelin in plasma of mice. Meanwhile, observations of the chromosomal aberrations and sperm head abnormalities were recorded. The administration of the anabolic agent pre-irradiation resulted in slightly non-significant amelioration in the pituitary hormone levels and in levels of PGE 2 and endothelin
In this podcast, Dr. David Swerdlow discusses prophylaxis after exposure to Coxiella burnetii. It is important to know who should be treated and how they should be treated after an intentional release with possible bioterrorism agents, including Coxiella burnetii. Created: 10/2/2008 by Emerging Infectious Diseases. Date Released: 10/2/2008.
Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1. Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID). Date Released: 7/18/2011.
The factors upon which the efficacy of stable iodine prophylaxis depends are reviewed, with particular reference to the dose of stable iodine, the timing of the dose, the influence of dietary iodine and the impact of the other prospective actions. The risks of stable iodine ingestion are estimated, and their application to the principle of Justification in outlined. (Author)
Objective: To determine the level of awareness, knowledge and practice of human immunodeficiency virus post exposure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnairebased survey conducted among paediatrcians that attended the Paediatric ...
Nov 23, 2015 ... Abstract: Objective: To deter- mine the level of awareness, knowledge and practice of human immunodeficiency virus post ex- posure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnaire- based survey conducted among paediatrcians that ...
Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian
Mallard, Simonette R; Gray, Andrew R; Houghton, Lisa A
In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a
Brown, Britni M; Stallings, Jon W; Clay, John S; Rhoads, Michelle L
The fertility of lactating Holstein cows is severely reduced during periods of heat stress. Despite this reduction in fertility, however, some inseminations conducted during heat stress result in successful pregnancies from which heifer calves are born. Many of these heifer calves are retained and raised to enter the milking herd as replacement animals. Heat stress experienced by these females around the time they were conceived may confer long-lasting effects that alter subsequent milk production capacity. The objective of this study was to examine the relationship between periconceptional heat stress and subsequent milk production of primiparous cows. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included Holstein cows that had completed at least one lactation in one of three states with large populations of dairy cattle and which are known for having hot, humid summers: Georgia, Florida or Texas. Dates of conception were calculated by subtracting 276 d from the recorded birth date of each individual cow. Records for cows conceived within the months of June, July, and August were retained as heat stress-conceived (HSC) cows (n = 94,440); cows conceived within the months of December, January, and February were retained as thermoneutral-conceived (TNC) contemporaries (n = 141,365). In order to account for the effects of environmental conditions on total milk production for a given lactation, cows were blocked by season of calving (winter, spring, summer or fall). Adjusted 305-day mature-equivalent milk production was evaluated with a mixed model ANOVA using SAS, in which random effects were used to account for variability between herds. Of the cows that calved in the summer, fall and winter, TNC cows had higher milk yield than the HSC cows in all states. Interestingly, the cows that calved in the spring presented a unique relationship, with HSC cows producing more milk. Overall however, heat stress at
Britni M Brown
Full Text Available The fertility of lactating Holstein cows is severely reduced during periods of heat stress. Despite this reduction in fertility, however, some inseminations conducted during heat stress result in successful pregnancies from which heifer calves are born. Many of these heifer calves are retained and raised to enter the milking herd as replacement animals. Heat stress experienced by these females around the time they were conceived may confer long-lasting effects that alter subsequent milk production capacity. The objective of this study was to examine the relationship between periconceptional heat stress and subsequent milk production of primiparous cows. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included Holstein cows that had completed at least one lactation in one of three states with large populations of dairy cattle and which are known for having hot, humid summers: Georgia, Florida or Texas. Dates of conception were calculated by subtracting 276 d from the recorded birth date of each individual cow. Records for cows conceived within the months of June, July, and August were retained as heat stress-conceived (HSC cows (n = 94,440; cows conceived within the months of December, January, and February were retained as thermoneutral-conceived (TNC contemporaries (n = 141,365. In order to account for the effects of environmental conditions on total milk production for a given lactation, cows were blocked by season of calving (winter, spring, summer or fall. Adjusted 305-day mature-equivalent milk production was evaluated with a mixed model ANOVA using SAS, in which random effects were used to account for variability between herds. Of the cows that calved in the summer, fall and winter, TNC cows had higher milk yield than the HSC cows in all states. Interestingly, the cows that calved in the spring presented a unique relationship, with HSC cows producing more milk. Overall however
Silver, A; Eichorn, A; Kral, J; Pickett, G; Barie, P; Pryor, V; Dearie, M B
Twenty-five percent of all nosocomial infections are wound infections. Professional guidelines support the timely use of preoperative prophylaxis for prevention of postoperative wound infections. Barriers exist in implementing this practice. IPRO, the New York State peer review organization, as part of the Health Care Financing Administration's Health Care Quality Improvement Program, sought to determine the proportion of patients receiving timely antibiotic prophylaxis for aortic grafts, hip replacements and colon resections in 44 hospitals in New York State. IPRO conducted a retrospective medical record review of 44 hospitals through out New York State stratified for teaching, nonteaching status. A sample was drawn of 2651 patients, 2256 from Medicare and 395 from Medicaid, undergoing either abdominal aortic aneurysm repair, partial or total hip replacement or large bowel resection. The study determined the proportion of patients who had documentation of receiving antibiotics and those who received antibiotics timely, that is less than or equal to 2 hours preoperatively. Eighty-six percent of patients had documentation of receiving an antibiotic. Forty-six percent of aneurysm repairs and 60% of hip replacements had evidence of receiving timely antibiotic prophylaxis, that is within 2 hours prior to surgery. For colon resections, 73% of cases had either oral prophylaxis or timely parenteral therapy. An increased proportion of patients had received parenteral antibiotics prematurely as the surgical start time occurred later in the day. A total of 44 different antibiotics were recorded for prophylaxis. Antibiotic prophylaxis was performed in 81% to 94% of cases, however, anywhere from 27% to 54% of all cases did not receive antibiotics in a timely fashion. By delegating implementation of ordered antibiotic prophylaxis to the anesthesia team, timing may be improved and the incidence of postoperative wound infections may decrease.
Thromboembolic events are a post-operative complication of arthroplasty surgery for up to 3 months. The incidence however, is not fully known. Some form of prophylaxis should be provided to all arthroplasty patients. Clinicians are wary of side effects, compliance profile and the associated cost. The objective of this study is to investigate practice patterns and their relevance to 3 risk groups. Ninety questionnaires were sent to orthopaedic surgeons with 3 hypothetical clinical scenarios and 10 prophylaxis regimes for thromboembolism across different risk groups. The response rate was 81\\/90 (90%). The most popular options in all 3 cases were early mobilisation, thrombo-embolism deterrant (TED) stockings and low molecular weight heparin (LMWH) (51\\/81, 62% of all cases). An inconsistent relationship exists between preferred practice and relevant guidelines. Preferred practice does not correlate with each level of risk.
Alberer, Martin; Löscher, Thomas
The prevention of infectious diseases by vaccination and by counselling about malaria prophylaxis is a central aspect of travel medicine. Besides mandatory vaccinations required for entry to certain countries various vaccinations may be indicated depending on destination and type of travel as well as on individual risks of the traveler. In addition, pre-travel counselling should always include a check-up of standard vaccinations. Protection against mosquito bites is the basis of malaria prophylaxis. The addition of chemoprophylaxis is warranted in high risk areas. When regular chemoprophylaxis is not applied it is recommended to carry an appropriate antimalarial drug which can be used for emergency stand-by treatment in case of unexplained fever and when medical attention is not available within 24 hours. Travelers should realize that self-treatment is a first-aid measure and that they should still seek medical advice as soon as possible. © Georg Thieme Verlag KG Stuttgart · New York.
Goodson, J Max; Palys, Michael D; Carpino, Elizabeth; Regan, Elizabeth O; Sweeney, Michael; Socransky, Sigmund S
Despite the common application of dental prophylaxis as part of patient therapy, there is little reported that describes the microbiological impact of this treatment. The authors gave 20 healthy college-aged subjects three dental prophylaxes with a fluoride-containing prophylaxis paste during a two-week period and instructed them in oral hygiene. They evaluated the microbiological composition of dental plaque samples collected before and after treatment using DNA probe analysis. They analyzed 40 representative bacterial species in seven bacterial complexes by checkerboard DNA-DNA hybridization assay techniques. After three dental prophylaxes, the patients' mean Gingival Index score decreased from 0.82 to 0.77, the mean Plaque Index score decreased from 0.72 to zero, and the total number of bacteria per tooth decreased to approximately one-third of the original number. The authors computed two different measures of bacterial presence. The reduction in bacterial numbers was statistically significant and occurred in many species. Bacterial proportion (DNA percentage or percentage of the bacteria per tooth) did not change significantly. Greater reductions in bacterial count occurred in species that showed high numbers before treatment. The total bacterial count decreased by approximately 72 percent of its original level before prophylaxis was initiated. Professional dental prophylaxis did not target any particular bacteria or bacterial groups but removed bacteria nonspecifically and in proportion to their initial numbers. Repeated dental prophylaxes effect a reduction in bacterial amount that is commensurate with the initial amount, but they do does not alter composition. This suggests that mild gingivitis may be a bacterially nonspecific effect of plaque accumulation and emphasizes the need for regular plaque removal to maintain optimal gingival health.
Lie, Shervi; Morrison, Janna L; Williams-Wyss, Olivia; Ozanne, Susan E; Zhang, Song; Walker, Simon K; Kleemann, David O; MacLaughlin, Severence M; Roberts, Claire T; McMillen, I Caroline
Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We hypothesized that maternal undernutrition during the periconceptional (PCUN: -60 to 7 days) and/or preimplantation (PIUN: 0-7 days) periods would result in a decrease in UCP1 expression and the abundance of insulin signaling molecules and an increase in the abundance of factors that regulate adipogenesis and lipogenesis in fetal perirenal adipose tissue (PAT) and that these effects would be different in singletons and twins. Maternal PCUN and PIUN resulted in a decrease in UCP1 expression in PAT, and PIUN resulted in higher circulating insulin concentrations, an increased abundance of pPKCζ and PDK4, and a decreased abundance of Akt1, phosphorylated mTOR, and PPARγ in PAT in singleton and twin fetuses. In singletons, there was also a decrease in the abundance of p110β in PAT in the PCUN and PIUN groups and an increase in total AMPKα in PAT in the PIUN group. In twins, however, there was an increase in the abundance of mTOR in the PCUN group and an increase in PDK2 and decrease in total AMPKα in the PIUN group. Thus exposure to periconceptional undernutrition programs changes in the thermogenic capacity and the insulin and fatty acid oxidation signaling pathway in visceral fat, and these effects are different in singletons and twins. These findings are important, as the thermogenic capacity of brown fat and the insulin sensitivity of visceral fat are important determinants of the risk of developing obesity and an insulin resistance phenotype in later life.
Chin-Pampillo, Juan Salvador; Masís-Mora, Mario; Ruiz-Hidalgo, Karla; Carazo-Rojas, Elizabeth; Rodríguez-Rodríguez, Carlos E
Biomixtures constitute the biologically active part of biopurification systems (BPS), which are used to treat pesticide-containing wastewater. The aim of this work was to determine whether co-application of chlorpyrifos (CLP) affects the removal of carbofuran (CFN) (both insecticide/nematicides) in a coconut fiber-compost-soil biomixture (FCS biomixture), after aging or previous exposure to CFN. Removal of CFN and two of its transformation products (3-hydroxycarbofuran and 3-ketocarbofuran) was enhanced in pre-exposed biomixtures in comparison to aged biomixtures. The co-application of CLP did not affect CFN removal, which suggests that CLP does not inhibit microbial populations in charge of CFN transformation. Contrary to the removal behavior, mineralization of radiolabeled (14)C-pesticides showed higher mineralization rates of CFN in aged biomixtures (with respect to freshly prepared or pre-exposed biomixtures). In the case of CLP, mineralization was favored in freshly prepared biomixtures, which could be ascribed to high sorption during aging and microbial inhibition by CFN in pre-exposure. Regardless of removal and mineralization results, toxicological assays revealed a steep decrease in the acute toxicity of the matrix on the microcrustacean Daphnia magna (over 97%) after 8days of treatment of individual pesticides or the mixture CFN/CLP. Results suggest that FCS biomixtures are suitable to be used in BPS for the treatment of wastewater in fields where both pesticides are employed. Copyright © 2016. Published by Elsevier B.V.
Lee, Seung Joo; Cha, Jihae; Lee, Jung Won
Pyelonephritis in infants is considered as a major factor for the formation of renal scar. To prevent recurrent pyelonephritis and renal damage, prophylaxis is extremely important. The aim of this study was to compare the effectiveness of probiotic and antibiotic prophylaxis or no-prophylaxis in infants with pyelonephritis and normal urinary tract. Altogether 191 infants, who were diagnosed with acute pyelonephritis, proven to have normal urinary tracts and followed up for 6 months on prophylaxis, were retrospectively evaluated. According to the types of prophylaxis, the infants were divided into three groups [probiotics (Lactobacillus species), antibiotics (trimethoprim/sulfamethoxazole, TMP/SMX), and noprophylaxis]. The incidence of recurrent urinary tract infection (UTI) during 6 months after the development of pyelonephritis, main causative uropathogens, and its antimicrobial sensitivities were compared. The incidence of recurrent UTI in the probiotic group was 8.2%, which was significantly lower than 20.6% in the no-prophylaxis group (P=0.035) and was not significantly different from 10.0% of the antibiotic group (P=0.532). The significant difference between the probiotic and no-prophylaxis groups was seen only in male infants (P=0.032). The main causative organism of recurrent UTI was Escherichia coli (E.coli), which was not different among the three groups (P=0.305). The resistance rate of E. coli to TMP/SMX was 100% in the antibiotic group, which was significantly higher than 25.0% in the probiotic group and 41.7% in the no-prophylaxis group (P=0.008). Probiotic prophylaxis was more effective in infants with pyelonephritis and normal urinary tract than in those with no-prophylaxis. It could be used as a natural alternative to antibiotic prophylaxis.
Chambers, H E; Pelish, P; Qiu, F; Florescu, D F
Practice variation regarding perioperative antimicrobial prophylaxis in total artificial heart transplantations (TAH-t) across institutions is unknown. The aim of our survey was to assess the current practices for prevention of infection in TAH-t recipients among different programs. An electronic survey was sent to programs that implant Syncardia TAH (Syncardia Systems, Tuscon, Ariz, USA). Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. The majority of centers (80.8%) had a formal surgical infection prophylaxis protocol. For non-penicillin-allergic patients, five (20.1%) institutions reported using a 4-drug regimen, seven (29.2%) used a 3-drug regimen, five (20.1%) used a 2-drug regimen, and seven (29.2%) used a cephalosporin alone. Similar data was seen in the penicillin-allergic patients. Infections were reported to occur postoperatively in 52.2% centers. During the first month after TAH-t, bacteremia represented 27.3%, driveline infections 27.2%, pulmonary infections 9%, and mediastinal infections 18.2%. The most common organisms seen within the first month were Candida spp., Escherichia coli, and Pseudomonas aeruginosa (21.4%). In 65% of centers, the mean rate of death post-TAH-t due to infection was 14.5% (SD, 22.3%). The mean rate of patients surviving until orthotopic heart transplantation was 58.6% (SD, 27.7%). Preventing infections post-TAH-t is key to decreasing morbidity and mortality. All institutions administered perioperative prophylaxis for TAH-t with significant variation among the centers. The majority of the centers have a formal perioperative prophylactic protocol. Copyright © 2017. Published by Elsevier Inc.
Beliakin, S A
Military doctors should have a uniform position to the use of alcohol. Now alcohol is the basic pathogenic factor in development of a lethal cirrhosis of a liver. The most known sayings justifying the use of alcohol, are insolvent. Useful doses of alcohol does not exist. The quantity of used alcohol has the great value. Only at achievement of age 21 year it is possible to use safe doses of alcohol. A safe dose of pure alcohol (ethanol) less than 30,0 in day. In a basis of prophylaxis of a cirrhosis of a liver there is a medical educational activity.
Jessica E Haberer
Full Text Available Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda, we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to 80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.
Oomens, Marjolijn A. E.; Forouzanfar, Tymour
Objective. Controversy exists about the efficacy of antibiotic prophylaxis in preventing complications after lower third molar surgery. For evidence-based recommendation, a review was performed on clinical trials reporting the use of antibiotic prophylaxis compared with no treatment or placebo with
Oomens, M.A.E.; Forouzanfar, T.
Objective Controversy exists about the efficacy of antibiotic prophylaxis in preventing complications after lower third molar surgery. For evidence-based recommendation, a review was performed on clinical trials reporting the use of antibiotic prophylaxis compared with no treatment or placebo with
Oomens, M.A.E.; Verlinden, C.; Goey, Y.; Forouzanfar, T.
There is no consensus on the use of antibiotic prophylaxis in orthognathic surgery to prevent infections. A systematic review of randomized controlled trials investigating the efficacy of antibiotic prophylaxis was performed to make evidence-based recommendations. A search of Embase, Ovid Medline,
Full Text Available The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology.THE STUDY WAS COMPLETED IN THREE PHASES: 1 An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2 A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3 In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach.A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration.Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.
Diorio, Caroline; Tomlinson, Deborah; Boydell, Katherine M; Regier, Dean A; Ethier, Marie-Chantal; Alli, Amanda; Alexander, Sarah; Gassas, Adam; Taylor, Jonathan; Kellow, Charis; Mills, Denise; Sung, Lillian
The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.
Conclusion: The high incidence of VTE-related complications indicates that the use of thromboprophylaxis is either insufficient or not matched to the level of risk. Updated guidelines on VTE prophylaxis should be used so that a standardized approach can ensure that patients receive adequate prophylaxis where indicated.
Kasteren, M.E.E. van
This thesis comprises several studies on the implementation of guidelines for antimicrobial use in prophylaxis as well as in therapy. The main part focuses on the data of the CHIPS-study; a quality improvement project of surgical prophylaxis in the Netherlands promoting prudent use of antibiotics
Juliana Ferreira da Silva Rios
Conclusion: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.
Huiras, Paul; Logan, Jill K; Papadopoulos, Stella; Whitney, Dana
Despite a lack of consensus guidelines, local antibiotic administration for prophylaxis of surgical site infections is used during many surgical procedures. The rationale behind this practice is to provide high antibiotic concentrations at the site of surgery while minimizing systemic exposure and adverse effects. Local antibiotic administration for surgical site prophylaxis has inherent limitations in that antibiotics are applied after the incision is made, rather than the current standard for surgical site prophylaxis that recommends providing adequate antibiotic concentrations at the site before the incision. The efficacy and safety of local application of antibiotics for surgical site prophylaxis have been assessed in different types of surgery with a variety of antibiotic agents and methods of application. We identified 22 prospective, randomized, controlled trials that evaluated local application of antibiotics for surgical site prophylaxis. These trials were subsequently divided and analyzed based on the type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and cardiothoracic. Methods of local application analyzed included irrigations, powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a significant lack of level I evidence supporting this practice for any of the surgical genres evaluated. In addition, the literature spans several decades, and changes in surgical procedures, systemic antibiotic prophylaxis, and microbial flora make conclusions difficult to determine. Based on available data, the efficacy of local antibiotic administration for the prophylaxis of surgical site infections remains uncertain, and recommendations supporting this practice for surgical site prophylaxis cannot be made. © 2012 Pharmacotherapy Publications, Inc.
ROSS, D E; KRAUT, J J
Cleansing and debridement is paramount in dealing with tetanus-prone wounds (severe crushing injuries, piercing wounds, blisters and burns are outstanding examples, particularly if contaminated with dirt, grass or other debris). Prophylaxis then is relatively easy in persons who have been actively immunized by toxoid injections. For them, a "booster" injection is indicated. Use of antitoxin, however, is hazardous, whether for prophylaxis or for treatment of the disease. Since it may in itself cause severe disease, including anaphylactic reaction and serum sickness, decision to use it must be weighed against the possibility of the development of tetanus in each case. To prepare for use of it, careful history should be taken, with particular reference to sensitivity to horse dander. Dermal tests, and perhaps ophthalmic tests, for sensitivity to the serum should be carried out. Even the tests may be hazardous and precautions should be taken accordingly. If it is decided that the use of antitoxin is necessary even though the patient is sensitive to the material, desensitization must be carried out promptly, with adequate preparation for severe reaction. There is experimental evidence that antibiotics of the tetracycline group, given soon after injury, may have prophylactic effect against tetanus.
Smythe, M A; Zarowitz, B J
To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent. Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles. Emphasis was placed on controlled trials conducted within the last 5 years. All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized. Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause-effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly. Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.
Pringsheim, Tamara; Davenport, W Jeptha; Mackie, Gordon; Worthington, Irene; Aubé, Michel; Christie, Suzanne N; Gladstone, Jonathan; Becker, Werner J
The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. This guideline is focused on patients with episodic migraine (headache on ≤ 14 days a month). Through a comprehensive search strategy, randomized, double blind, controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane reviews were identified. Studies were graded according to criteria developed by the US Preventive Services Task Force. Recommendations were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. In addition, a general literature review and expert consensus were used for aspects of prophylactic therapy for which randomized controlled trials are not available. Prophylactic drug choice should be based on evidence for efficacy, side-effect profile, migraine clinical features, and co-existing disorders. Based on our review, 11 prophylactic drugs received a strong recommendation for use (topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, butterbur, riboflavin, coenzyme Q10, and magnesium citrate) and 6 received a weak recommendation (divalproex sodium, flunarizine, pizotifen, venlafaxine, verapamil, and lisinopril). Quality of evidence for different medications varied from high to low. Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations. These strategies included: first time strategies for patients who have not had prophylaxis before (a beta-blocker and a tricyclic strategy), low side effect strategies (including both drug and herbal/vitamin/mineral strategies), a strategy for patients with high body mass index, strategies for patients with co-existent hypertension or with co-existent depression and /or
D G Deshmukh
Full Text Available Only sporadic reports of failure of post-exposure prophylaxis for rabies exist in the published literature. We are reporting such a case in a 3-year-old boy. The child had Category III dog bite on his right thigh. He presented with progressive ascending paralysis, finally developing quadriplegia and respiratory paralysis. Typical hydrophobia and aerophobia were absent. He received four doses of antirabies cell culture vaccine. He did not receive antirabies immunoglobulin. The boy succumbed on the 23 rd day of the dog bite. Diagnosis of rabies was confirmed in the laboratory by demonstration of Negri bodies, direct fluorescent antibody test and reverse transcriptase-polymerase chain reaction either on impression smear of brain or a piece of brain taken during autopsy.
Surgical site infections (SSI) are very common, and represent more than 20% of all hospital-acquired infections. SSIs are associated with a higher mortality, as well as to an extended hospital stay and costs, depending on the surgical procedure and type of SSI. Advances in control practices for these infections include improvement in operating room ventilation, sterilization methods, barriers, and surgical techniques, as well as in surgical antimicrobial prophylaxis. For the latter, the antimicrobial agent should: be active against the most common pathogens, be administered in an appropriate dosage and in a time frame to ensure serum and tissue concentrations over the period of potential contamination, be safe, and be administered over the shortest effective time period to minimize adverse events, development of resistances, and cost. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Clayton, Edward H; Lamb, Tracy A; Refshauge, Gordon; Kerr, Matthew J; Bailes, Kristy L; Ponnampalam, Eric N; Friend, Michael A; Hopkins, David L
Algae high in docosahexaenoic acid (DHA) may provide a source of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) for inclusion in the diet of lambs to improve the LCn-3PUFA status of meat. The effect of background LCn-3PUFA status on the metabolism of high DHA algae is, however, unknown. The aim of the current study was to determine whether the response to a high in DHA algae supplement fed to lambs for six weeks prior to slaughter was mediated by a maternal periconceptional diet. Forty Poll Dorset × Border Leicester × Merino weaner lambs were allocated to receive either a ration based on oat grain, lupin grain, and chopped lucerne (control) or the control ration with DHA-Gold™ algae included at 1.92 % DM (Algae) based on whether the dams of lambs had previously been fed a diet high in n-3 or n-6 around conception. LCn-3PUFA concentration was determined in plasma and red blood cells (RBC) prior to and following feeding. The concentrations of EPA and DHA in the plasma and RBC of lambs receiving the control ration were significantly (p DHA were also significantly (p DHA was, however, significantly (p DHA.
Ord, James; Fazeli, Alireza; Watt, Penelope J
Stress represents an unavoidable aspect of human life, and pathologies associated with dysregulation of stress mechanisms - particularly psychiatric disorders - represent a significant global health problem. While it has long been observed that levels of stress experienced in the periconception period may greatly affect the offspring's risk of psychiatric disorders, the mechanisms underlying these associations are not yet comprehensively understood. In order to address this question, this chapter will take a 'top-down' approach, by first defining stress and associated concepts, before exploring the mechanistic basis of the stress response in the form of the hypothalamic-pituitary-adrenal (HPA) axis, and how dysregulation of the HPA axis can impede our mental and physical health, primarily via imbalances in glucocorticoids (GCs) and their corresponding receptors (GRs) in the brain. The current extent of knowledge pertaining to the impact of stress on developmental programming and epigenetic inheritance is then extensively discussed, including the role of chromatin remodelling associated with specific HPA axis-related genes and the possible role of regulatory RNAs as messengers of environmental stress both in the intrauterine environment and across the germ line. Furthering our understanding of the role of stress on embryonic development is crucial if we are to increase our predictive power of disease risk and devise-effective treatments and intervention strategies.
GAO Lei; CUI Shan Shan; HAN Yu; DAI Wei; SU Yuan Yuan; ZHANG Xin
Objective This study aimed to explore the association between periconceptional fish consumption by parents and autism spectrum disorder (ASD) and intelligence deficiency (ID). Methods A case-control study was conducted through a questionnaire with 108 ASD cases, 79 ID cases, and 108 controls. The ASD and ID cases were students from special educational schools in Tianjin from 2012 to 2014. The age- and sex-matched controls were from a high school, three primary schools, and a kindergarten in Tianjin. Multivariate logistic regression was performed. Results Paternal habit of eating hairtail before fertilization, maternal preference for fruits during pregnancy, and maternal habit of eating grass carp during pregnancy were preventive factors for ASD. Paternal habit of drinking alcohol before fertilization was a risk factor for ID, whereas maternal preference for fruits during pregnancy and maternal habit of eating crucian carp during pregnancy were protective factors for ID. Conclusion Parental fish consumption is beneficial for the prevention of ASD and ID. Meanwhile, the protective effects of fish consumption on ASD and ID differ. More attention should be paid to the combined effect of other food when eating fish.
Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M
To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.
Full Text Available Infective endocarditis (IE is an infection of the endocardium and/or heart valves with the formation of a thrombus and secondary damage of the involved tissue, with significant mortality and severe complications. The prevention of bacterial endocarditis is of great controversy. Antimicrobial prophylaxis is usable in the prevention of endocarditis by killing bacteria before or after their extension to the damaged endocardium. No human studies offer strong evidence to support the efficacy of antibiotic prophylaxis so far, thus it could be potentially dangerous. Therefore, the European Society of Cardiology (ESC may need to reconsider and update the previous guidelines with the proposal of reducing the prophylactic approach of IE. The 2015 Task Force recommends prophylaxis for highest risk patients undergoing highest risk procedures, focused on prevention rather than prophylaxis of IE, especially in nosocomial endocarditis.
William F. Griffith
Full Text Available The objective of this report is to describe an urban county hospital human immunodeficiency virus (HIV infection prevention protocol offering prophylactic combination antiretroviral medications to female victims of sexual assault. A retrospective chart review was conducted from June, 2007 through June, 2008 of 151 women who were prescribed antiretroviral prophylaxis by protocol. All women receiving HIV prophylaxis initially screened HIV seronegative. Of the 58 women who reported taking any HIV prophylaxis, 36 (62% were HIV screened at 12 and/or 24 weeks and none had HIV seroconverted. Although the initiation of an HIV post exposure prophylaxis protocol for sexual assault in a county hospital population is feasible, patient follow-up for counseling and HIV serostatus evaluation is an identified barrier
Full Text Available We conducted a retrospective case series study to evaluate the safety of fosfluconazole prophylaxis for preventing invasive fungal infection in VLBW infants with a central vascular access. Fosfluconazole was administered intravenously at a dose of 6 mg/kg everyday during which time a central venous catheter was placed. A total of 23 infants met the criteria for enrollment in our study. No cases of fungal infection were detected during the central venous catheter placement in the group. None of the infants had an elevated β-D-glucan, and all of them were still alive at discharge. Regarding the liver and renal function, no statistically significant differences were observed before and at the end of fosfluconazole prophylaxis. The results of this study demonstrate that fosfluconazole prophylaxis in preventing invasive fungal infection was well tolerated by VLBW infants. This is a first report to describe antifungal prophylaxis using fosfluconazole for VLBW infants.
MacFarlane, T W; McGowan, D A; Hunter, K; MacKenzie, D
The antibiotic sensitivity pattern of bacteria isolated from bacteraemia after dental extraction was compared with that of bacteria isolated from dental plaque samples from the same patient. The results supported the current practice of using penicillin and erythromycin empirically for prophylaxis. The prediction of the most appropriate antibiotic for prophylaxis using dental plaque samples was most accurate when the minimum inhibitory concentration (MIC) of plaque isolates were used. It appe...
Byrne, Stephen; Weaver, Daniel Timothy
Although preventable, venous thromboembolism remains a common cause of hospital acquired morbidity and mortality. Guidelines, such as the one produced by the American College of Chest Physicians (ACCP), are aimed at reducing hospital associated venous thromboemboli. Unfortunately the majority of studies have revealed inadequate adherence to these guidelines. The objective of this study was to evaluate the use of venous thromboembolism prophylaxis at Cork University Hospital. Cork University Hospital, Wilton, Cork, Ireland. Data from the patient's chart, drug kardex and laboratory results were recorded during April 2010. A Caprini score, a venous thromboembolism risk factor assessment tool, was subsequently calculated for each patient based on data collected. Appropriate prophylaxis was determined after examining data collected, Caprini score and prophylactic regime according to the ACCP 8th edition guidelines. Primary outcome was to analyse adherence to VTE prophylaxis guidelines. A total of 394 patients met the inclusion criteria and were reviewed, of which, 60% (n = 236) were medical and 37% (n = 146) were surgical patients. In total 63% of patients received some form of venous thromboembolism prophylaxis. Furthermore, 54% of medical and 76% of surgical patients received prophylaxis. However only 37% of the patients studied received appropriate thromboprophylaxis according to the ACCP 8th edition guidelines (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). Additionally 51% of surgical and 27% of medical patients received appropriate prophylaxis. Data collected from Cork University Hospital revealed poor adherence to international venous thromboembolism prophylaxis guidelines. As stated in the ACCP 8th edition guidelines, every hospital should develop a formal strategy for venous thromboembolism prevention (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). In order to improve adherence to guidelines, Cork University Hospital should develop, implement and
Bonnar, Paul E; Senthinathan, Arrani; Nakamachi, Yoshiko; Backstein, David J; Steinberg, Marilyn; Morris, Andrew M
Abstract Background Surgical site infections are common causes of healthcare-associated infections. Using surgical antimicrobial prophylaxis (SAP) is a complex process that can reduce these rates if performed correctly. While antimicrobial stewardship programs have developed guidelines for SAP, there has been less focus on understanding and modifying the behavioral and contextual factors required to optimize prophylaxis use. We performed chart reviews and workflow analyses to develop interven...
Jonker, Emile F F; Visser, Leonardus G
The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: email@example.com
Full Text Available BACKGROUND: The appropriate use of antibiotics prophylaxis in the prevention and reduction in the incidence of surgical site infection is widespread. This study evaluates the appropriateness of the prescription of antibiotics prophylaxis prior to surgery amongst hospitalized patients in the geographic area of Avellino, Caserta, and Naples (Italy and the factors associated with a poor adherence. METHODS: A sample of 382 patients admitted to 23 surgical wards and undergoing surgery in five hospitals were randomly selected. RESULTS: Perioperative antibiotic prophylaxis was appropriate in 18.1% of cases. The multivariate logistic regression analysis showed that patients with hypoalbuminemia, with a clinical infection, with a wound clean were more likely to receive an appropriate antibiotic prophylaxis. Compared with patients with an American Society of Anesthesiologists (ASA score ≥4, those with a score of 2 were correlated with a 64% reduction in the odds of having an appropriate prophylaxis. The appropriateness of the timing of prophylactic antibiotic administration was observed in 53.4% of the procedures. Multivariate logistic regression model showed that such appropriateness was more frequent in older patients, in those admitted in general surgery wards, in those not having been underwent an endoscopic surgery, in those with a higher length of surgery, and in patients with ASA score 1 when a score ≥4 was chosen as the reference category. The most common antibiotics used inappropriately were ceftazidime, sultamicillin, levofloxacin, and teicoplanin. CONCLUSIONS: Educational interventions are needed to improve perioperative appropriate antibiotic prophylaxis.
Tagliaferri, A; Franchini, M; Coppola, A; Rivolta, G F; Santoro, C; Rossetti, G; Feola, G; Zanon, E; Dragani, A; Iannaccaro, P; Radossi, P; Mannucci, P M
While primary prophylaxis is a well-established and recommended method of care delivery for children with severe haemophilia, fewer studies have documented the benefits of secondary prophylaxis started in adolescence or adulthood. To evaluate the role of secondary prophylaxis started in adolescent and adult severe haemophiliacs, a retrospective observational cohort study was conducted in 10 Italian Centres that investigated 84 haemophiliacs who had bled frequently and had thus switched from on-demand to prophylactic treatment during adolescence (n = 30) or adulthood (n = 54). The consumption of clotting factor concentrates, the orthopaedic and radiological scores, quality of life and disease-related morbidity were compared before and after starting secondary prophylaxis. Prophylaxis reduced the mean annual number of total and joint bleeds (35.8 vs. 4.2 and 32.4 vs. 3.3; P work/school (34.6 vs. 3.0, P life. With respect to on-demand treatment, higher factor consumption and cost of secondary prophylaxis were balanced by marked clinical benefits and greater well-being in this cohort of adolescent/adult haemophiliacs.
Rios, Juliana Ferreira da Silva; Camargos, Paulo Augusto Moreira; Corrêa, Luísa Petri; Romanelli, Roberta Maia de Castro
This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.
Schürks, Markus; Diener, Hans-Christoph; Goadsby, Peter
Migraine prophylaxis is a stepwise procedure with lifestyle advice followed by consideration of medications. Patients should be advised to try to maintain a regular lifestyle, with regular sleep, meals, exercise, and management of stress, perhaps through relaxation techniques or other ways that are sensible for them. If this regimen does not adequately control their migraines, preventatives are indicated. Patients can choose between evidence-based nutraceuticals such as riboflavin, feverfew, butterbur, or coenzyme Q10, or more traditional pharmacotherapeutics. Medicine choices are somewhat limited by what is available in each country, but from the full range, the medicines of first choice are beta-adrenoceptor blockers, flunarizine, topiramate, and valproic acid. Beta-adrenoceptor blockers are particularly useful in patients also suffering from hypertension or tachycardia. Following recent studies, topiramate has become a first choice for episodic as well as chronic migraine. It is the only prophylactic drug that may lead to weight loss, but it is sometimes associated with adverse cognitive effects. Valproic acid and flunarizine also have very good prophylactic properties. However, valproic acid is often associated with adverse effects, and flunarizine is unavailable in many countries, including the United States. If sequential monotherapies are ineffective, combinations of first-line drugs should be tried before advancing to drugs of second choice, which are associated with more adverse effects or have less well-established prophylactic properties. Amitriptyline should be used carefully because of its anticholinergic effects, although it is useful in comorbid tension-type headache, depression, and sleep disorders. Methysergide is very effective, but it has been supplanted or even made unavailable in many countries because of its well-described association with retroperitoneal fibrosis. Pizotifen has a slightly better safety profile but is unavailable in the United
Rozendaal, Anna M.; Essen, Anthonie J. van; Meerman, Gerard J. te; Bakker, Marian K.; Biezen, Jan J. van der; Goorhuis-Brouwer, Sieneke M.; Vermeij-Keers, Christl; Walle, Hermien E. K. de
Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0–12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19–2.49), especially of cleft lip/alveolus (3.16, 1.69–5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects—mainly clefts of the lip/alveolus—with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to
Pellegrini, Vincent D
Venous thromboembolism remains the most common cause of hospital readmission and death after total joint arthroplasty. The 2008 American College of Chest Physicians (ACCP) guidelines, based on prospective randomized clinical trials with a venography endpoint, endorse the use of low-molecular-weight heparin, fondaparinux, or adjusted dose warfarin (target international normalized ratio, 2.5; range, 2-3) for up to 35 days after total hip arthroplasty (THA) and total knee arthroplasty (TKA). In the past, the ACCP has recommended against the use of aspirin, graduated compression stockings, or venous compression devices as the sole means of prophylaxis, but in 2008 they first recommended the "optimal use of mechanical thromboprophylaxis with venous foot pumps or intermittent pneumatic compression devices" in patients undergoing total joint arthroplasty who "have a high risk of bleeding." When the high risk subsides, pharmacologic thromboprophylaxis is substituted for, or added to, mechanical methods. Fractionated heparins and pentasaccharide are the most effective agents in reducing venographic deep venous thrombosis (DVT) after total joint arthroplasty with residual clot rates rates. Low-intensity warfarin (target international normalized ratio, 2.0) combines safety (bleeding rates exchange for a lower bleeding rate; genetic testing will likely simplify warfarin use and reduce outlier responders. Copyright 2010, SLACK Incorporated.
Ahmed, M.; Asghar, I.; Mansoor, N.
To find out the incidence of surgical site infection in clean general surgery cases operated without prophylactic antibiotics. One hundred and twenty-four clean surgical cases operated without antibiotic prophylaxis between July 2003 and December 2004, were studied and these were compared with similar number of cases who received antibiotics. The data was collected and analyzed using software SPSS (version 10.0). Chi-square and student-t test were used to analyze the association between antibiotics and wound infection. The most frequent operation was repair of various hernias, 69.3% in group A and 75% in group B. More operations were carried out between 21-30 years, 38.7% in group A and 41.9% in group B. Surgical site infection occurred in one patient (0.8%) in each group. Chi-square test (0.636) applied to group A and B showed no association of infection and administration/ no administration of antibiotics (p > 0.25). The t-test applied on group A and B (t=0) also showed no significant difference between administration of antibiotics/ no-antibiotics and infection (p > 0.25). The use of prophylactic antibiotic in clean, non implant and elective cases is unnecessary. (author)
Cundiff David K