Re: Pre-Exposure Prophylaxis for Mitigating Risk of HIV Transmission During HIV Cure–Related Clinical Trials With a Treatment Interruption

To the Editor—The article by Lelièvre [1] and his reference to that by Lelièvre and Hocqueloux [2] discuss whether preexposure prophylaxis (PrEP) should be provided to the partners of HIV-positive research participants who undergo analytical treatment interruptions (ATIs) in HIV cure research. Lelièvre and Hocqueloux argue that new analyses of data from the 2006 SMART study [3] show that ATIs do not compromise health when initiated in people with high CD4 counts and no previous HIV-related illness [1].

While the ethics of ATIs have been contested elsewhere [4], we argue that the evidence supporting U = U [5] makes it feasible for sexual partners of HIV-positive research participants to use their partners’ undetectable viral load to protect themselves against HIV transmission. Thus, the viral rebound that results from an ATI can place sexual partners at risk, as highlighted by Lelièvre and Hocqueloux [2].

The ethical questions raised here are whether sex partners of participants in the study should have been offered PrEP, and should PrEP be offered in future ATI studies. Lelièvre [1] argues that the provision of PrEP as a standard of prevention for partners may not be appropriate for several reasons; he claims there is lack of evidence on the efficacy of PrEP as an HIV prevention tool when there is viral rebound and he suggests PrEP has lower efficacy for women. He also claims that offering PrEP to trial participants who have multiple sex partners is challenging. Finally, he ponders whether offering PrEP to trial participants’ partners when they cannot otherwise access it might constitute an “unfair inequality”.

In response, although we accept that there are feasibility issues for PrEP access where trial participants have multiple sex partners, we argue that none of these issues justifies withholding PrEP from people placed at increased risk of HIV acquisition by their partners’ research participation. Studies providing PrEP for partners of trial participants enrolled in ATIs are unique opportunities to gather the needed data on the efficacy of PrEP when there is viral rebound, identified as a gray research area by Lelièvre [1].

Also, Lelièvre’s PrEP analysis does not compare like with like when he compares results from PROUD and IPERGAY studies, conducted predominantly in men who have sex with men after the time that PrEP efficacy was established, with Partners PrEP and TDF2 [6], which are studies conducted before this was established. Further, the low efficacy of PrEP reported in the studies that recruited women was only a result of poor adherence [7].

While PrEP access by sex partners of study participants with multiple sex partners might not be feasible, we argue that it is both feasible and obligatory to offer PrEP to their stable sex partner(s). Offering PrEP to sex partners is not an unfair inequality because were it not for the study, the undetectable viral load of their HIV-positive sexual partner would protect these individuals. Research participants and their spouses placed at increased risk of HIV acquisition by their partners’ research participation, are owed special protections because of their selfless act that ultimately results in global benefit.

Further, the contributions of HIV research participants justifies the inclusion of PrEP as part of the standard prevention package for all biomedical HIV prevention trials irrespective of the public health policies of countries where trials are being conducted. Ethics guidelines [8] requires they have “access to all state of the art HIV risk reduction methods” like PrEP. The Step and Phambili HIV vaccine trials [9] raised the moral consciousness of the need to protect all clinical trial participants by providing state of the art prevention tools as soon as possible, irrespective of national guidelines. Concerns about raising dichotomies through PrEP provision is not a valid ethical justification, as dichotomies are inherently created in biomedical HIV prevention trials [10]; the nonprovision of PrEP is not the remedy.

The possibility of HIV infection of sex partners of study participants enrolled in ATIs studies indicates that trialists need to institute practices that reduce the risk of harm. Trials should counsel participants about HIV infection transmission risk to sex partners, the need for their sex partners’ access to HIV prevention packages including PrEP, and arrange for sex partners’ counselling and access to the HIV prevention packages. In the absence of specific guidelines on third-party care in ATIs, the moral obligation of care to everyone at risk of HIV infection in any biomedical HIV clinical trial is enough reason to provide PrEP to study participants based on its proven efficacy for all sexes.

Note

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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