Demonstrating Safety and Effective Delivery of Daily Oral Pre-exposure Prophylaxis (PrEP) for Sex Workers in India
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Female sex workers (FSWs) in India are at high risk of HIV infection, and while correct and
      consistent condom use is an effective means of preventing HIV transmission, many FSWs have
      difficulty insisting on their use. Alternative HIV prevention options are needed for FSWs who
      are unable to correctly and consistently use condoms with their clients or regular partners.
      Oral pre-exposure prophylaxis (PrEP) may be an important tool to fill this critical
      prevention gap, and a demonstration project is required to assess the impact and feasibility
      of the use of PrEP as an HIV prevention intervention among most at risk FSWs in India.

      The proposed project will take place at two sites in India and will assess the use of a risk
      assessment tool to identify FSWs who would most benefit from PrEP, collect information about
      the reasons why FSWs choose to accept or decline PrEP, evaluate two different PrEP delivery
      strategies (weekly clinic pick-up or home delivery by peer educators every second day),
      monitor adherence to and discontinuation of PrEP, and evaluate unintended consequences of the
      use of PrEP in these communities (e.g. reduction of condom use, drug side effects or adverse
      events, social harms or resistance). To ensure the safety of study participants, a community
      advisory board will be set up and will meet regularly to inform study staff of any concerns
      that the community may have related to the study, so that the study staff can respond in a
      timely manner. A data safety and monitoring board will also be established to monitor
      participant safety.
    

Detailed description: 
      This PrEP demonstration study is designed to assess the feasibility and impact of delivering
      PrEP in addition to the existing package of HIV prevention interventions available to female
      sex workers in India. The study aims to: 1) identify female sex workers in need of HIV
      prevention and willing to take PrEP; 2) evaluate sustained uptake and adherence to oral PrEP;
      3) assess safe delivery of PrEP; and 4) demonstrate effective delivery of PrEP within the
      context of the National Program of Targeted Interventions. The study will be implemented in
      two regions and among two typologies of female sex workers in India: brothel-based FSWs in
      Kolkata and FSWs operating from different settings in Mysore and Mandya.

      Outcome 1: Identification of female sex workers in need of HIV prevention and willing to take
      oral PrEP For optimal delivery with limited resources, it is critical to provide HIV
      prevention strategies such as PrEP to populations at greatest risk of infection. Female sex
      workers are an important population for HIV prevention in India, prioritized as a "core high
      risk group" for targeted interventions by the India National AIDS Control Organization (NACO)
      (NACO 2013 annual report). In particular, some FSWs report inconsistent condom use and have
      unmet needs for HIV prevention (Ramesh, 2010; Reza-Paul, 2008). For example, these women may
      be less empowered or able to consistently demand condom use by their clients or may wish to
      become pregnant. PrEP has the potential to be an additional, more acceptable and effective
      HIV prevention method for female sex workers who have difficulty using condoms consistently.

      This study proposes the development and use of a risk screening tool to identify female sex
      workers who are most vulnerable to HIV. This tool will guide recruitment into the
      demonstration study and could later assist health providers in deciding who will benefit most
      from PrEP for HIV prevention. In addition, this study will assess the proportion of FSWs
      identified by the risk screening tool who are willing to take PrEP. Quantitative and
      qualitative evaluations will identify factors related to the decision to initiate PrEP as
      well as reasons why FSWs decline PrEP.

      Outcome 2: Sustained uptake and adherence to oral PrEP among female sex workers Similar to
      all medications, sustained uptake and adherence to PrEP is fundamental for efficacy in
      preventing HIV acquisition. In the four clinical trials of oral PrEP that demonstrated
      efficacy, study participants with high adherence had the greatest protection from HIV (Baeten
      2012, Choopanya 2013, Grant 2010, Thigpen 2012). Likewise, across PrEP trials, there was a
      clear relationship between higher efficacy and a greater proportion of participants with
      study drug detectable in their blood. Two randomized clinical trials of daily oral PrEP among
      heterosexual women in Africa found no efficacy for HIV prevention; poor adherence to PrEP
      most likely explains these results (Marrazzo 2013, Van Damme 2012). For example, drug level
      testing in the FEM-PrEP Study found that less than 40% of a random sample of HIV negative
      women in the PrEP arm of the study had detectable levels of PrEP in their blood (Van Damme
      2012). Analyses of high-risk subgroups of study participants in the Partners PrEP Study found
      PrEP efficacy estimates ranged from 64 to 84%, showing consistently high efficacy of PrEP in
      preventing HIV across various higher risk groups, including women (Murnane 2013).

      Preliminary community awareness campaigns for PrEP among female sex workers in Kolkata found
      high interest in PrEP - approximately 80% reported willingness to take daily, oral PrEP. Sex
      workers in Mysore-Mandya are engaged in series of consultations where information related to
      PrEP as a tool for combination prevention is being discussed and questions or concerns
      related to PrEP addressed. In both places, initial observations show that there are some sex
      workers (e.g. those who are on long time contracts, those with overnight clients where
      sometimes the number of clients are not disclosed, those who want to be pregnant, and those
      who do not use condoms with their regular partners) expressed interest in being part of the
      demonstration project.

      This PrEP demonstration study will assess the acceptability and feasibility of two approaches
      to PrEP delivery: 1) peer educator delivery every other day; or 2) weekly clinic pick-up.
      Study staff will measure PrEP initiation, adherence and discontinuation. They will record
      these events in participant records, and quarterly visits will be used to assess adherence
      through biological tests and questionnaires. PrEP will be delivered as part of a package of
      HIV prevention services, and therefore use of other prevention strategies, such as condom
      use, will also be monitored. The full package of prevention services will continue to be
      provided to FSWs with the support of India's national government and in accordance with
      national guidelines.

      Data on drug adherence and condom use will be collected through various means. An
      ethnographic study will be designed to understand factors that may promote or impede
      adherence to PrEP, as well as changes in risk behaviour (reduction in condom use). In
      addition to this, peer educators will use a pictorial tool to document these items (e.g.,
      frequency and patterns of sexual activity, condom use, and PrEP use). The study will also
      include a biological measure of PrEP adherence through the assessment of drug-levels in the
      blood.

      Regular counselling about HIV prevention and PrEP will be provided to study participants to
      promote adherence. In a sub-sample of study participants, an electronic adherence monitoring
      device to measure and promote adherence, Helping Hands, will be tested (De Blaser 2010). The
      Helping Hands device is complimented by a web platform that illustrates patient-specific data
      to monitor dosing history and adherence patterns.

      Outcome 3: Oral HIV PrEP as part of a combined prevention package delivered safely for female
      sex workers Four randomized controlled trials have demonstrated that daily, oral PrEP is safe
      for HIV-uninfected women in a wide range of settings; these antiretrovirals have been proven
      safe for HIV-infected women for many years of use. The most common side effects of FTC/TDF
      are minor and short-lived (i.e. first several weeks). This study will provide evidence for
      the safe delivery of oral PrEP to female sex workers in brothel and street-based settings in
      India. Quarterly clinic visits will assess physical health, side effects, adverse events and
      any other social harms or concerns with PrEP use. This study will invest in continuous
      engagement with communities of female sex workers according to good participatory practice
      guidelines to provide correct information about PrEP, keep communities continuously engaged,
      and maintain adherence to PrEP.

      A community advisory board (CAB) and a Data Safety and Monitoring Board (DSMB) will be set
      up. The CAB will meet monthly and on an as needed basis. It will inform study staff of any
      concerns that the community may have related to the study, so that the study staff can
      respond in a timely manner. The CAB members will be close to the community and will be able
      to respond to community concerns by calling meetings to address issues in a timely manner.
      The DSMB will be set up to ensure that the rights of the study participants are safeguarded
      in a transparent fashion, and to monitor their safety by scrutinizing any adverse events. The
      DSMB will also help to respond to concerns raised by the CAB. The DSMB will include an
      ethicist, a human rights lawyer, representatives from University of Manitoba, WHO and UNAIDS,
      representatives from the global network of sex workers, and a statistician. In addition,
      ongoing qualitative research and monitoring by research staff, as well as outreach by peer
      educators, will attempt to identify any community resistance, rumours or actual harms, and
      respond in an appropriate manner.

      Outcome 4: Effective delivery of oral HIV PrEP demonstrated in context of National Program of
      Targeted Interventions This study proposes to deliver PrEP within the context of the National
      Program of Targeted Interventions in order to demonstrate that PrEP is feasible in "real
      world" settings. DMSC and Ashodaya currently implement targeted intervention programs for
      female sex workers in Kolkata and Mysore/Mandya, respectively. These programs provide
      outreach by peer educators and outreach workers, clinic services (e.g. HIV testing and
      counseling, STI screening and treatment), and referrals for HIV care and treatment for
      brothel- and street-based FSWs. This study will evaluate the addition of PrEP to this
      existing service delivery model. It will also show willingness of participants to enroll in a
      demonstration study and to use oral PrEP without reimbursements or incentives for
      participation.

      Study findings can inform national and local government's decision to adopt PrEP as a new HIV
      prevention strategy. Development of HIV prevention packages, provider training, quality
      management and service delivery guidelines in line with national systems will provide
      guidance for real life implementation of PrEP, and also contribute to the larger goal of
      providing standards for the delivery of HIV prevention interventions.

      Risk Mitigation Identification of willing participants: The development of a tool to
      correctly identify those FSWs at continued risk of HIV infection does not ensure that those
      women will be willing to take PrEP. Though initial interest in PrEP is strong in Sonagachi
      among FSWs in general, women at highest risk may be different. A feasibility study to
      identify levels of awareness about PrEP, perceptions and misconceptions about PrEP, and
      optimum ways to present PrEP accurately to identify those women at greatest need with
      greatest interest in using PrEP is about to begin in Mysore.

      Research ethics: All study materials will be submitted for approval by the institutional
      review boards of Durbar Mahila Samanwaya Committee (DMSC) Ethical Committee, the World Health
      Organization (WHO) Ethics Review Committee (ERC), the University of Manitoba (UM) Health
      Research Ethics Board (HREB), and by the Indian Council on Medical Research (ICMR) through
      the Health Ministry's Screening Committee (HMSC). The procedures, risks, and benefits of
      study participation will be explained to all potential study participants and informed
      consent will be obtained from those who are willing to participate prior to their
      participation in the study. The project will follow all guidelines for human subjects
      research as mandated by the Government of India, as this is the location of the proposed
      project. In addition to this, a Data Safety and Monitoring Board will be established at
      Ashodaya to monitor the safety of participants and the scientific integrity of the study
      across all study sites.

      Community advisory board (CAB): A community advisory board will be set up in each study site,
      and will meet regularly to inform study staff and the DSMB of any concerns that the community
      may have related to the study, so that the study staff can respond in a timely manner.

      Data Safety and Monitoring Board (DSMB): A DSMB will be established to ensure that the rights
      of all study participants from each site, Ashodaya and DMSC, are safeguarded, and to monitor
      their safety by scrutinizing any adverse events. They will also respond to concerns raised by
      the CABs from each site. The DSMB will include an ethicist, a human rights lawyer,
      representatives from the University of Manitoba, WHO and UNAIDS, representatives from the
      global network of sex workers, and a statistician.
    

Intervention name(s): Truvada
Intervention type(s): Drug
Intervention description(s): The demonstration project will use a prospective cohort design, enrolling individuals and following them up at multiple intervals over the course of 16 months. Study participants will be asked to take one tablet of Truvada daily, as HIV Pre-Exposure Prophylaxis, over this period. They will be asked to attend 7 regular visits at the project sites over the course of the project. In between visits, they will receive peer educator home visits every other day, as part of regular DMSC (Kolkata) and Ashodaya (Mysore/Mandya) outreach prevention activities. We plan to enroll 2000 female sex workers equally split between the two sites.
Other intervention name(s): emtricitabine and tenofovir disoproxil fumarate
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV; AIDS; India; Prevention; Female sex workers; PrEP; Pre-exposure prophylaxis; Truvada; Tenofovir