The paradox of HIV prevention: did biomedical prevention trials show how effective behavioral prevention can be?

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access (PTA) to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale multicentre HIV prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA.

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Strengthening HIV-prevention trials: a dose of implementation science?

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(18)30567-x ◽

2018 ◽

Vol 18 (11) ◽

pp. 1166-1168 ◽

Cited By ~ 3

Author(s):

Elvin H Geng ◽

David V Glidden ◽

Nancy Padian

Keyword(s):

Hiv Prevention ◽

Implementation Science ◽

Prevention Trials

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Innovative Approaches to Obtain Minors’ Consent for Biomedical HIV Prevention Trials: Multi-Site Quasi-Experimental Study of Adolescent and Parent Perspectives

JMIR Research Protocols ◽

10.2196/16509 ◽

2020 ◽

Vol 9 (3) ◽

pp. e16509 ◽

Cited By ~ 1

Author(s):

Amelia Knopf ◽

Mary A Ott ◽

Claire Burke Draucker ◽

J Dennis Fortenberry ◽

Daniel H Reirden ◽

...

Keyword(s):

Hiv Prevention ◽

Parental Involvement ◽

Human Subjects ◽

Consent Process ◽

Parental Consent ◽

Open Label ◽

Open Label Study ◽

Biomedical Hiv Prevention ◽

Quasi Experimental ◽

Prevention Trials

Background Despite the high burden of new HIV infections in minor adolescents, they are often excluded from biomedical HIV prevention trials, largely owing to the ethical complexities of obtaining consent for enrollment. Researchers and ethics regulators have a duty to protect adolescents—as a special category of human subjects, they must have protection that extends beyond those afforded to all human subjects. Typically, additional protection includes parental consent for enrollment. However, parental consent can present a risk of harm for minor adolescents. Research involving minor adolescents indicate that they are unwilling to join biomedical trials for stigmatized health problems, such as HIV, when parental consent is required. This presents a significant barrier to progress in adolescent HIV prevention by creating delays in research and the translation of new scientific evidence generated in biomedical trials in adult populations. Objective This protocol aims to examine how parental involvement in the consent process affects the acceptability of hypothetical participation in biomedical HIV prevention trials from the perspectives of minor adolescents and parents of minor adolescents. Methods In this protocol, we use a quasi-experimental design that involves a simulated consent process for 2 different HIV prevention trials. The first trial is modeled after an open-label study of the use of tenofovir disoproxil fumarate and emtricitabine as preexposure prophylaxis for HIV. The second trial is modeled after a phase IIa trial of an injectable HIV integrase inhibitor. There are 2 groups in the study—minor adolescents aged 14 to 17 years, inclusive, and parents of minor adolescents in the same age range. The adolescent participants are randomized to 1 of 3 consent conditions with varying degrees of parental involvement. After undergoing a simulated consent process, they rate their willingness to participate (WTP) in each of the 2 trials if offered the opportunity. The primary outcome is WTP, given the consent condition. Parents undergo a similar process but are asked to rate the acceptability of each of the 3 consent conditions. The primary outcome is acceptability of the consent method for enrollment. The secondary outcomes include the following: capacity to consent among both participant groups, the prevalence of medical mistrust, and the effects of the study phase (eg, phase IIa vs the open-label study) and drug administration route (eg, oral vs injection) on WTP (adolescents) and acceptability (parents) of the consent method. Results Enrollment began in April 2018 and ended mid-September 2019. Data are being analyzed and dissemination is expected in April 2020. Conclusions The study will provide the needed empirical data about minor adolescents’ and parents’ perspectives on consent methods for minors. The evidence generated can be used to guide investigators and ethics regulators in the design of consent processes for biomedical HIV prevention trials. International Registered Report Identifier (IRRID) DERR1-10.2196/16509

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Tomorrow’s HIV Prevention Trials of Vaccines and Antibodies

Statistical Communications in Infectious Diseases ◽

10.1515/scid-2019-0007 ◽

2019 ◽

Vol 11 (1) ◽

Author(s):

Dean Follmann

Keyword(s):

Hiv Prevention ◽

Hiv Infection ◽

Infection Rate ◽

Infection Risk ◽

Effective Interventions ◽

Prevention Trials ◽

Prevention Methods ◽

Regression Adjustment ◽

Baseline Covariates ◽

Historical Controls

Abstract Effective HIV prevention has the potential to change the landscape of HIV prevention trials. Low infection rates will make superiority studies necessarily large while non-inferiority trials will need some evidence that a counterfactual placebo group had a meaningful HIV infection rate in order to provide evidence of effective interventions. This paper explores these challenges in the context of immune related interventions of mAbs and vaccines. We discuss the issue of effect modification in the presence of PrEP, where subjects on PrEP may have less of a benefit of a mAb or (vaccine) than subjects off PrEP. We also discuss different methods of placebo infection rate imputation. We estimate infection risk as a function of mAb level (or vaccine induced immune response) in the mAb (or vaccine) arm and then extrapolate this infection risk to zero mAbs as a proxy for the placebo infection rate. Important aspects are the use of triangulation or multiple methods to impute the placebo infection rate, concern about extrapolation if few mAbs are close to zero, and the use of currently available data with placebo groups to rigorously evaluate the accuracy of imputation methods. We also discuss use of historical controls and some generalizations of the idea of (DMurray, J. 2019. “Regulatory Perspectives for Streamlining HIV Prevention Trials.” Statistical Communications in Infectious Diseases.) to use rectal gonorrhea rates to impute HIV infection rate. Generalizations include regression adjustment to calibrate for potential differences in baseline covariates for ongoing vs historical studies and the use of the gonorrhea, HIV relationship in a contemporaneous observational study. Examples of recent and ongoing trials of malaria chemoprophylaxis and HPV vaccines, where extremely effect prevention methods are available, are provided.

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