The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing.

BACKGROUND: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. METHODS: This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. RESULTS: The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7). CONCLUSION: The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed.

Advancing the regulatory path on hepatitis B virus treatment and curative research: a stakeholders consultation.

Hepatitis B infection remains a significant disease burden around the world, with an estimated two billion individuals infected and 350 million living with chronic hepatitis B. Current antivirals are efficacious, but require lifelong treatment for the majority of infected individuals. The field is galvanised to improve diagnostics and treatment with the goal to develop shorter, finite treatments leading to viral control after treatment discontinuation. Achievement of complete and functional cure is challenged by the complexity of the virus life cycle, the lack of adequate preclinical models, the cccDNA-mediated persistence of HBV in liver cells, the lack of validated biomarkers to predict viral control and cure, and the probable need for combination treatment involving antiviral- and immune-based strategies. Experts from diverse stakeholder groups participating in the HBV Forum (a project of the Forum for Collaborative Research) contributed their expertise and perspective to resolving issues and overcoming barriers in the regulatory path for novel HBV therapeutic strategies; addressing gaps in preclinical models, diagnostics, clinical trial design, biomarkers and endpoints, and public health efforts. Interviewees highlighted the need for open and collaborative ongoing dialogues among stakeholders in a neutral space as a critical process to move the field forwards. The Forum model facilitates dialogue and deliberation of this nature, with dedicated experts from all stakeholder groups participating. The promise of an HBV cure is exciting. Now is the time to work together toward that goal.

PrEP: controversy, agency and ownership.

Pre-exposure prophylaxis (PrEP) has been and continues to be an intervention that causes controversy and debate between stakeholders involved in providing or advocating for it, and within communities in need of it. These controversies extend beyond the intrinsically complex issues of making it available. In this commentary, some of the possible roots of the air of dissent and drama that accompanies PrEP are explored. The similarities between the controversies that dogged the earliest human trials of PrEP and the ones we see today in the era of licensing and implementation are explored. We outline five mediating principles or cultural norms that may influence arguments about PrEP differently. Three areas of specific concern are identified: medical risk versus benefit, distrust and fear of healthcare interventions, and fears for individual responsibility and community cohesion. The fear that PrEP may somehow represent a loss of control over one or more of these domains is suggested as an underlying factor. The development of countervailing measures, to institute greater community "ownership" of PrEP, and concomitant improvements in the sense of individual agency over sexual risk are outlined and recommended.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention.

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 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. DISCUSSION: 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. CONCLUSIONS: 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.

Acceptability of drug detection monitoring among participants in an open-label pre-exposure prophylaxis study.

In the world of HIV pre-exposure prophylaxis (PrEP) research, there is emerging interest in providing study participants with pharmacokinetic results from drug level testing to guide adherence counseling. The iPrEx randomized control trial was the first study to produce meaningful results of PrEP in humans. In the iPrEx open-label extension (OLE) study, blood plasma samples collected in the first 12 weeks of study participation were tested for the presence of tenofovir/emtricitabine--the drugs which compromise PrEP. Study clinicians shared results (detectable/undetectable) with participants at their 24-week visit. We evaluated the acceptability of receiving these results among a subset of iPrEx OLE participants. We conducted in-depth interviews (n = 59) with participants (those with and those without drug detected) enrolled in Boston, Chicago, and San Francisco to assess their experiences with receiving drug detection feedback. Incorporating drug detection results into the clinical study visit was well received and no negative reactions were expressed. For about half of participants, receiving their drug detection lab result was useful while for others it was not important. In a few cases, no drug detected results led to increased efforts to take PrEP consistently and in most cases enhanced open discussion of missed doses. Participants reported a desire for greater specificity, particularly quantitative drug levels needed for protection. We recommend exploring strategies to increase the salience of drug level results, including using feedback to target adherence counseling, and reducing the time between specimen collection, testing, and receipt of results. Future studies should evaluate the feasibility and impact of providing more specific quantitative drug levels using biomarkers of longer term PrEP exposure, i.e., hair/dried blood spots.

Study product adherence measurement in the iPrEx placebo-controlled trial: concordance with drug detection.

OBJECTIVE: To evaluate the concordance between adherence estimated by self-report (in-person interview or computer-assisted self-interview), in-clinic pill counts, and pharmacy dispensation records and drug detection among participants in a placebo-controlled pre-exposure prophylaxis HIV prevention trial (iPrEx). DESIGN: Cross-sectional evaluation of 510 participants who had drug concentration data and matched adherence assessments from their week-24 study visit. METHODS: Self-reported adherence collected through (1) interview and (2) computer-assisted self-interview surveys, (3) adherence estimated by pill count, and (4) medication possession ratio was contrasted to having a detectable level of drug concentrations [either tenofovir diphosphate (TFV-DP) or emtricitabine triphosphate (FTC-TP)], as well as to having evidence of consistent dosing (tenofovir diphosphate ≥ 16 fmol/106 cells), focusing on positive predictive values, overall and by research site. RESULTS: Overall, self-report and pharmacy records suggested high rates of product use (over 90% adherence); however, large discrepancies between these measures and drug detection were noted, which varied considerably between sites (positive predictive values from 34% to 62%). Measures of adherence performed generally well in the US sites but had poor accuracy in other research locations. Medication possession ratio outperformed other measures but still had relatively low discrimination. CONCLUSIONS: The sizable discrepancy between adherence measures and drug detection in certain regions highlights the potential contribution of factors that may have incentivized efforts to seem adherent. Understanding the processes driving adherence reporting in some settings, but not others, is essential for finding effective ways to increase accuracy in measurement of product use and may generalize to promotion efforts for open-label pre-exposure prophylaxis.

HIV pre-exposure prophylaxis in men who have sex with men and transgender women: a secondary analysis of a phase 3 randomised controlled efficacy trial.

BACKGROUND: For maximum effect pre-exposure prophylaxis should be targeted to the subpopulations that account for the largest proportion of infections (population-attributable fraction [PAF]) and for whom the number needed to treat (NNT) to prevent infection is lowest. We aimed to estimate the PAF and NNT of participants in the iPrEx (Pre-Exposure Prophylaxis Initiative) trial. METHODS: The iPrEx study was a randomised controlled efficacy trial of pre-exposure prophylaxis with coformulated tenofovir disoproxil fumarate and emtricitabine in 2499 men who have sex with men (MSM) and transgender women. Participants aged 18 years or older who were male at birth were enrolled from 11 trial sites in Brazil, Ecuador, Peru, South Africa, Thailand, and the USA. Participants were randomly assigned (1:1) to receive either a pill with active pre-exposure prophylaxis or placebo, taken daily. We calculated the association between demographic and risk behaviour during screening and subsequent seroconversion among placebo recipients using a Poisson model, and we calculated the PAF and NNT for risk behaviour subgroups. The iPrEx trial is registered with ClinicalTrials.gov, NCT00458393. FINDINGS: Patients were enrolled between July 10, 2007, and Dec 17, 2009, and were followed up until Nov 21, 2010. Of the 2499 MSM and transgender women in the iPrEx trial, 1251 were assigned to pre-exposure prophylaxis and 1248 to placebo. 83 of 1248 patients in the placebo group became infected with HIV during follow-up. Participants reporting receptive anal intercourse without a condom seroconverted significantly more often than those reporting no anal sex without a condom (adjusted hazard ratio [AHR] 5·11, 95% CI 1·55-16·79). The overall PAF for MSM and transgender women reporting receptive anal intercourse without a condom was 64% (prevalence 60%). Most of this risk came from receptive anal intercourse without a condom with partners with unknown serostatus (PAF 53%, prevalence 54%, AHR 4·76, 95% CI 1·44-15·71); by contrast, the PAF for receptive anal intercourse without a condom with an HIV-positive partner was 1% (prevalence 1%, AHR 7·11, 95% CI 0·70-72·75). The overall NNT per year for the cohort was 62 (95% CI 44-147). NNTs were lowest for MSM and transgender women self-reporting receptive anal intercourse without a condom (NNT 36), cocaine use (12), or a sexually transmitted infection (41). Having one partner and insertive anal sex without a condom had the highest NNTs (100 and 77, respectively). INTERPRETATION: Pre-exposure prophylaxis may be most effective at a population level if targeted toward MSM and transgender women who report receptive anal intercourse without a condom, even if they perceive their partners to be HIV negative. Substance use history and testing for STIs should also inform individual decisions to start pre-exposure prophylaxis. Consideration of the PAF and NNT can aid in discussion of the benefits and risks of pre-exposure prophylaxis with MSM and transgender women. FUNDING: National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation.

Participant experiences and facilitators and barriers to pill use among men who have sex with men in the iPrEx pre-exposure prophylaxis trial in San Francisco.

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.

Facilitators and barriers to medication adherence in an HIV prevention study among men who have sex with men in the iPrEx study in Chiang Mai, Thailand.

In 2008, the Pre-exposure Prophylaxis Initiative (iPrEx) study expanded to include men who have sex with men (MSM) in Chiang Mai, Thailand. In full, 114 participants from Chiang Mai joined this international double-blinded trial of daily FTC-TDF (Truvada®) or placebo as a pre-exposure prophylaxis (PrEP) HIV prevention strategy. To better understand the characteristics of iPrEx participants specifically from this underserved population in Thailand, and gain insights into their experiences of trying to take a daily tablet as part of this blinded PrEP trial, we conducted a qualitative study. In 2010, 32 MSM iPrEx participants provided in-depth interviews and an additional 14 joined focus group discussions. Results of the qualitative analyzes suggested that participants held generally positive attitudes toward the iPrEx study and study medication and related this to high rates of adherence to the daily regimen. Participants also reflected on the provision of quality health care as part of participation in the trial, as well as support from clinical research staff, family and friends as helpful in supporting high rates of study medication adherence. Discourse concerning challenges to adherence included medication taking behavior, which was contextualized by lifestyle, living arrangement, social life, social stigma in terms of being mistakenly identified as HIV positive or unintentional disclosure of sexual identity to family and friends, and relationship conflicts with partners. The results provide broader perspectives of participant experiences of the study medication and daily adherence in the larger contexts of the MSM community, close relationships, and the study climate, and can be leveraged in constructing PrEP adherence support approaches within these communities.

Supporting study product use and accuracy in self-report in the iPrEx study: next step counseling and neutral assessment.

The recent successes of biomedical HIV prevention approaches have sparked considerable debate over the scalability, feasibility, and acceptability of pre-exposure prophylaxis (PrEP) as a widespread prevention strategy for men who have sex with men and trans-gender. Anticipated difficulties with PrEP adherence and concerns about resources required to best support it have tempered enthusiasm of PrEP demonstration projects and roll-out. While no evidence-based approach for supporting PrEP use is presently available, a number of approaches have been developed in the context of double-blind, randomized, placebo-controlled trials of PrEP that can provide guidance in moving forward with real world support of open label PrEP use. We present the development, implementation and evaluation of feasibility and acceptability of next-step counseling (NSC) and neutral assessment (NA), the adherence support and promotion of accurate reporting approaches used in the late phases of the iPrEx study. Evaluation of the approach from the perspective of implementers of over 15,000 NSC sessions in seven different countries with almost 2,000 iPrEx participants provided support for NSC, its brevity (averaging ~14 min per follow-up session) and overall acceptability and feasibility. NA also was generally well supported, with a majority of study staff believing this approach was feasible and acceptable; however, lower acceptability for certain aspects of NA was noted amongst staff reporting NA was different from their previous interview approach. Quantitative and qualitative data gathered from implementers were used to make modifications for supporting PrEP use in the open-label extension of iPrEx.

Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.

BACKGROUND: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. METHODS: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. RESULTS: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). CONCLUSIONS: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).

Building community partnerships: case studies of Community Advisory Boards at research sites in Peru, Zimbabwe, and Thailand.

BACKGROUND: Differences in resources, knowledge, and infrastructure between countries initiating and countries hosting HIV prevention research trials frequently yield ethical dilemmas. Community Advisory Boards (CABs) have emerged as one strategy for establishing partnerships between researchers and host communities to promote community consultation in socially sensitive research. PURPOSE: To understand the evolution of CABs and community partnerships at international research sites conducting HIV prevention trials. METHODS: Three research sites of the HIV Prevention Trials Network (HPTN) were selected to include geographical representation and diverse populations at risk for HIV/AIDS - in Lima, Peru; Chitungwiza, Zimbabwe; and Chiang Mai, Thailand. Data collection included review of secondary data, including academic publications and site-specific progress reports; observations at the research sites; face-to-face interviews with CAB members, research staff, and other key informants; and focus groups with study participants. Rapid assessment techniques were used for data analysis. RESULTS: Two of the three CABs developed new strategies for community representation in response to new studies. All three CABs expanded their original function and became advocates for broader community interests beyond HIV prevention. The participation and input of community representatives, in response to critical incidents that occurred at the sites over the past five years, helped to solidify partnerships between researchers and communities. LIMITATIONS: Rapid Assessment is an exploratory methodology designed to provide an understanding of a situation based on the integration of multiple data sources, collected within a short period of time, without a formal examination of transcribed and coded data. Case studies, as a method, are meant to draw out what can be learned from a single case but are not, in the scientific sense, generalizable. CONCLUSIONS: In developing countries, CABs can be dynamic entities that enhance the HIV research process, assist in responding to issues involving research ethics, and prepare communities for HIV research.

Role versatility among men who have sex with men in urban Peru.

Role versatility refers to the practice in which individual men who have sex with men (MSM) play both insertive and receptive sexual roles over time. Versatility has been thought to be relatively uncommon among Latin American MSM but possibly rising. Versatility has also been shown to be a potentially large population-level risk factor for HIV infection. In this study we examine the correlates of versatile behavior and identity among 2,655 MSM in six Peruvian cities. Versatile behavior with recent male partners was found in 9% of men and versatile ("moderno") identity was reported by 16%. Significant predictors included high education, white-collar occupation, sex work, and residence in Lima. Age was not significant in any analysis. Since sex work is negatively correlated with other predictors, versatile men appear to comprise two distinct sub-populations. Insertive-only men appear to play a strong role in bridging the HIV epidemic between MSM and women.

HIV-1, sexually transmitted infections, and sexual behavior trends among men who have sex with men in Lima, Peru.

OBJECTIVE: To assess and estimate trends in HIV, sexually transmitted infections (STIs), and sexual behavior among men who have sex with men (MSM) in Lima, Peru. DESIGN: Second-generation HIV sentinel surveillance surveys conducted in 1996, 1998, 2000, and 2002. METHODS: Adult men reporting sex with at least 1 man during the previous year were eligible to participate. Sexual behavior and serum HIV-1 and syphilis antibodies were assessed. HIV seroincidence was estimated by a sensitive/less-sensitive enzyme immunoassay strategy. Rectal and pharyngeal swabs for Neisseria gonorrhoeae culture and a first-void urine sample for urethral leukocytes for presumptive diagnosis of urethritis were obtained. Herpes simplex virus 2 (HSV-2) antibodies were measured in 2002. RESULTS: Although HIV prevalence increased from 18.5% to 22.3% from 1996 through 2002, bacterial prevalence declined significantly for syphilis (16.0% to 12.4%), early syphilis (8.6% to 3.4%), and rectal gonorrhea (5.1% to 0.2%). High HIV seroincidence was estimated, with the lowest (4.8%) incidence in 1998. In 2002, HSV-2 seroprevalence was 51.0%. After adjustment for age, education, and self-reported sexual identity, our data suggest that a yearly increase by 6% in the prevalence of HIV occurred among MSM in Lima, with a corresponding decline in syphilis (by 9%), early syphilis (by 18%), and rectal gonorrhea (by 64%). Condom use during last sexual intercourse increased by 26% each year with the most recent male steady partner and, among non-sex workers, by 11% with the most recent casual partner. CONCLUSIONS: HIV continued to spread among MSM in Lima even when a decline in bacterial STIs and increase in condom use were estimated to occur. Intensification of medical and behavior prevention interventions is warranted for MSM in Peru.

HIV, syphilis and heterosexual bridging among Peruvian men who have sex with men.

OBJECTIVES: To determine prevalence of and risk factors associated with HIV and syphilis seropositivity and estimate incidence of HIV infection among Peruvian men who have sex with men (MSM) and characterize behaviors of men who report sex with both men and women ('bridgers'). DESIGN: Cross-sectional study of MSM in Lima, Peru. METHODS: Four-hundred and fifty-one MSM (of whom 442 responded to the question regarding sexual orientation) recruited through street outreach. Each was interviewed and underwent serologic testing for syphilis and HIV, including the less sensitive enzyme immunoassay test to estimate HIV incidence. RESULTS: Overall, HIV and syphilis prevalence were 18.5% and 16.0%, respectively, with highest prevalence among cross-dressers (33.3% and 51.1%, respectively). The estimated overall HIV seroincidence was 11.2% per year (95% confidence interval, 4.8-23.6). Overall, 47.1% of men reported ever having sex with a woman: 78.6% of men self-identifying as heterosexuals, 85.1% of bisexuals, 35.5% of homosexuals, and 12.5% of cross-dressers. Of these, 26.5% were 'bridgers', of whom 55% reported two or more female partners during the last year. 'Bridgers' were less likely to have always used condoms during the past year for vaginal sex (17%) than for insertive anal sex with men (25.5%). CONCLUSIONS: Among MSM in Peru, HIV and syphilis prevalence and HIV incidence were high, especially among cross-dressers. The high prevalence of bisexuality and low rates of consistent condom use, especially with female sexual partners indicates potential HIV transmission into the heterosexual population.

Entrenando a profesores de secundaria en educación sexual y prevención de SIDA y enfermedades de transmisión sexual en Lima / Training high-school teachers in sexual education and AIDS/STD prevention in Lima, Peru

Presenta los resultados del Taller piloto de capacitación en educación sexual y para la prevención del SIDA, ETS y embarazo no deseado, que tuvo lugar en Lima en abril de 1990 para profesores de secundaria. Fue presentado en el Encuentro Latinoamericano sobre Intervenciones Educativas para la Prevención de SIDA y Enfermedades de Transmisión Sexual, llevado a cabo en Kingston, Jamaica del 11 al 14 de diciembre de 1990