Ethics of Ancillary Care in Clinical Trials in Low Income Countries: A Nigerian Case Study

The ethical conduct of HIV prevention researchers is subject to scrutiny. Many clinical trials take place in low and middle income countries where HIV incidence is high, but the benefits of research are often first enjoyed in high income countries. The provision of ancillary care – medical care provided to clinical trial participants during a trial, which is not related to the research question – is one way in which trial  participants can receive direct benefits from their participation in research. We argue that such care is a legitimate benefit of research participation. This care does not constitute ‘undue inducement’ if the research study itself involves minimal risk and is subject to ethical and regulatory oversight. We also  argue that research teams working with populations who have sub-optimal healthcare access have a duty to provide ancillary care within agreed limits. These limits should be negotiated to ensure that the  research remains feasible and economically viable. (Afr J Reprod Health 2014; 18[3]: 135-142)Keywords: Ancillary care; ethics, HIV prevention, undue inducementLa conduite éthique des chercheurs dans le domaine de la prévention du VIH est soumise au contrôle. De nombreux essais cliniques ont lieu dans les pays à faible et moyen revenu où l'incidence du VIH est élevée, mais les avantages de la recherche sont souvent d'abord appréciés dans les pays à revenu élevé. La prestation de soins auxiliaires – les soins médicaux fournis aux participants des essais cliniques au cours d'un procès, qui n'est pas liée à la question de la recherche - est une façon pour les participants à l'essai de recevoir des prestations directes pour leur participation à la recherche. Nous soutenons que ces soins constituent un bénéfice légitime de participation à la recherche. Ce soin ne constitue pas «une incitation indue» si l'étude elle-même implique un risque minimal et elle est soumise à la surveillance éthique et réglementaire. Nous soutenons également qu’il incombe aux équipes de recherche qui  travaillent avec les populations qui ont accès à des soins de santé sous-optimal de leur fournir des soins auxiliaires dans les limites convenues. Ces limites doivent être négociées pour s'assurer que la recherche demeure réalisable et économiquement viable. (Afr J Reprod Health 2014; 18[3]: 135-142)Mots-clés: Soins auxiliaires, éthique, prévention du VIH, incitations indue

Development of Guidelines for the Conduct of HIV Research Monitoring by Ethics Committees in Nigeria

Nigerian research ethics committees are charged with the responsibility to monitor ongoing research to  ensure compliance with ethical standards. Recent evidence from qualitative studies on research conduct however, indicate that many research studies fail to implement their protocols as written, and that this is not  reported due to a failure of comprehensive monitoring. As Nigeria is in many respects a highly suitable country  in which to conduct HIV biomedical prevention research, we argue there is a need to reprioritise the  strengthening of the monitoring capacity of ethics committees so that such vital and ethically complex  research can be conducted with confidence. We identify the need for (i) improved resourcing and training of  ethics committee members, and (ii) comprehensive planning of research monitoring as part of the ethics  committee protocol review process. We also highlight the significance of community collaboration and the establishment of a central pool of national monitors, as essential components for reinvigorating monitoring capacity. (Afr J Reprod Health 2014; 18[3]: 66-73)Keywords: Ethics, monitoring, HIV prevention, complianc

Standards and Guidelines for HIV Prevention Research: Considerations for Local Context in the Interpretation of Global Ethical Standards

While international standards are important for conducting clinical research, they may require interpretation in particular contexts. Standard of care in HIV prevention research is now complicated, given that there are now two new biomedical prevention interventions – ‘treatment-as-prevention’, and pre-exposure prophylaxis – in addition to barrier protection, counselling, male circumcision and treatment of sexually transmissible  infections. Proper standards of care must be considered with regard to both normative guidance and the  circumstances of the particular stakeholders – the community, trial population, researchers and sponsors. In addition, the special circumstances of the lives of participants need to be acknowledged in designing trial protocols and study procedures. When researchers are faced with the dilemma of interpretation of  international ethics guidelines and the realities of the daily lives of persons and their practices, the decisions of the local ethics committee become crucial. The challenge then becomes how familiar ethics committee  members in these local settings are with these guidelines, and how their interpretation and use in the local  context ensures the respect for persons and communities. It also includes justice and the fair selection of  study participants without compromising data quality, and ensuring that the risks for study participants and their community do not outweigh the potential benefits. (Afr J Reprod Health 2014; 18[3]: 55-65)Keyword: Standards of prevention, ancillary care, local context, ethical guidelines, researc

Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15-1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555

Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15-1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555

Validation of participant eligibility for pre-exposure prophylaxis: Baseline data from the <i>PRELUDE</i> demonstration project

<div><p>Background</p><p>In Australia, pre-exposure prophylaxis (PrEP) is targeted to individuals at high risk for HIV infection. We describe the HIV risk profile and characteristics of <i>PRELUDE</i> participants, and evaluate the population validity of the sample in representing high-risk gay and bisexual men (GBM) eligible for PrEP.</p><p>Methods</p><p><i>PRELUDE</i> is an on-going, open-label, single-arm observational study. Participants were identified in clinics and screened for eligibility using a paper-based risk assessment tool which followed the New South Wales (NSW) PrEP guidelines. Selection was validated using an independent online behavioural survey, completed by study participants upon enrolment. Demographic information was analysed using descriptive statistics, and kappa tests were used to determine agreement between reporting of high-risk practices in the risk assessment and behavioural survey.</p><p>Results</p><p>During 2014–15, 471 individuals were targeted for enrolment; 341 were assessed for PrEP eligibility and 313 were enrolled. Of these, 303 (97%) identified as GBM. Overall, 85% of GBM met at least one high-risk criterion; 68% reported receptive intercourse with an HIV-positive or unknown status casual male partner, and 37% reported methamphetamine use in the three months preceding enrolment. The remaining 15% were enrolled based on medium-risk behaviours, or at the clinicians’ discretion. We found an 82% total agreement between self-reported high-risk behaviour and clinicians’ categorisation of GBM as being at high risk for HIV based on PrEP eligibility criteria.</p><p>Conclusions</p><p>Behavioural eligibility criteria used by clinicians successfully identified individuals at high risk for HIV infection. This targeted approach ensures that the greatest public health and HIV prevention benefits can be derived in a setting without universal access to PrEP.</p></div

Comparison of high-risk behaviours reported in the paper-based risk assessment and online behavioural survey (n = 305).

<p>HR1: Had an HIV-positive regular partner with whom condoms were not consistently used; HR2: Had receptive intercourse with a casual male partner of HIV-positive or unknown status; HR3: Been diagnosed rectal chlamydia or gonorrhoea; HR4: Methamphetamine use.</p

New South Wales HIV pre-exposure prophylaxis behavioural eligibility criteria for gay and bisexual men.

<p>New South Wales HIV pre-exposure prophylaxis behavioural eligibility criteria for gay and bisexual men.</p