HIV Seroconversion Despite PrEP Therapy

The study evaluated a cohort of 14 young black, men who have sex with men in Atlanta, Georgia, who had HIV seroconversion despite treatment with PrEP.

The tragedy of continued HIV transmission in the era of pre-exposure prophylaxis (PrEP) is explored in detail in a viewpoint article published in Clinical Infectious Diseases.1 The study evaluated a cohort of 14 young black men who have sex with men (MSM) in Atlanta, Georgia, who experienced HIV seroconversion despite administration of PrEP as part of the EleMENt Study.

The EleMENt Study is an ongoing prospective observational cohort design that looks specifically at young black MSM. Recruiting since 2015, the study aims to better understand the complex relationship between substances and sexual risk behaviors. Young black MSM are known to have a particularly high incidence of HIV and suboptimal levels of PrEP uptake. To date, the study has reported a 6.2% annual incidence of HIV at an interim analysis despite access to free PrEP services.

Real-world reasons for HIV seroconversion in the setting of free or low-cost PrEP access are categorized into 5 distinct typologies in this study. All 300 young black MSM currently enrolled were offered PrEP at their first visit. Of the 14 individuals with incident HIV infections identified, 1 experienced biomedical failure (likely seroconversion at the time of PrEP initiation), 1 had low PrEP adherence, 2 discontinued PrEP, 5 were in the contemplation phase, and another 5 refused treatment.

Maintaining adequate protection requires 4 or more doses of tenofovir/emtricitabine a week. The individual with low adherence did not maintain his treatment as a result of travel and forgetting to take his medication. Adequate PrEP adherence in other individuals was likely maintained via enrollment in a text message reminder service and the use of a keychain pill holder for emergency doses.

Of the 2 individuals who seroconverted after PrEP discontinuation, 1 stopped PrEP due to a medical illness and was unable to restart immediately following recovery due to expiration of his patient assistance program. Other reasons given included drug adverse effects, a change in perception of risk, and “pill fatigue.”

Pre-contemplation is defined as patient unwillingness to believe they are appropriate candidates for PrEP. Remaining in the PrEP contemplation stage was a common scenario in patients who seroconverted. Previous investigations of the PrEP Motivational Cascade have suggested that “pre-contemplation” on the Transtheoretical Model of Change occurred in 53% of eligible individuals (23% contemplation, 11% preparation, 4% PrEP action, 9% maintenance and adherence).4

The 5 individuals who refused PrEP gave as reasons such as concern regarding medication adverse effects, a mistrust of the medical establishment, or an aversion to taking pills. In other studies, participants also reported a fear of sexual disinhibition and stigma.

These typologies suggest that interventions are best targeted to the early stages of the PrEP care cascade. Public health activity to improve awareness of risk in young black MSM communities is essential and advocacy for the safety and benefits of PrEP should be paramount at the individual level.

Infectious Disease Advisor talked to Dr David Serota of the department of medicine, division of infectious diseases, Emory University School of Medicine in Atlanta, Georgia.

Infectious Disease Advisor: Your study highlights that the fact that PrEP failures are rarely biomedical and far more frequently related to part of the PrEP care continuum. What part of this continuum is most amenable to intervention?

David Serota, MD: There are things we can do to mitigate each of the contributing typologies of PrEP failure. To truly optimize PrEP, we need to make progress in all of these areas. In our study, we have had the best success as the result of our research staff using a “PrEP navigator” to avoid systems failures, PrEP contemplation, and PrEP discontinuation-related seroconversions. They are responsible for managing prescriptions, lab testing, and patient assistance program paperwork/renewals. They also re-offer PrEP to participants who have previously stated they weren’t interested and follow up with participants who have stopped taking PrEP. We are also studying a smartphone app to support adherence in individuals who have started PrEP.

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Infectious Disease Advisor: PrEP Contemplation and PrEP Refusal typologies account for 10 of the 14 HIV seroconversions observed. Are there evidence-based approaches to support these individuals and encourage initiation of treatment?

Dr Serota: PrEP refusal has heterogeneous causes, and many are difficult to address, including broad societal forces such as stigma, low health literacy, misperception of HIV risk, and competing life priorities. I think motivational interviewing techniques can be implemented in this space. I am interested in ongoing research evaluating whether a “health promotion” message about PrEP is more effective for getting folks on PrEP and adherent compared with the more traditional “risk indoctrination” approach.2,3

Infectious Disease Advisor: Is further research is needed to better understand the reasons for stop/start behaviour?

Dr Serota: Absolutely. Finding mechanisms to maximize PrEP persistence (a combination of adherence to tenofovir plus emtricitabine and treatment continuation over periods of possible HIV exposure) is the next big goal in PrEP scale-up. We know PrEP works in clinical trials and demonstration projects, but it is another big step to establish effectiveness on a broader scale. We are only just now beginning to understand patterns of PrEP use and we are also studying predictors of later PrEP discontinuation with the goal of pre-emptively intervening in order to bolster adherence prior to discontinuation.


Advancing beyond the biomedical and understanding the complex personal, social, and healthcare-related factors involved with PrEP use is crucial to improving uptake.


1. Serota D P, Rosenberg E S, Lockard, A. M., et al. Beyond the biomedical: PrEP failures in a cohort of young black men who have sex with men [published online April 7, 2018]. Clin. Inf. Dis. doi:10.1093/cid/ciy297/4964699

2. Golub SA, Pena S, Hilley A, Pachankis J, Radix A. Brief behavioral intervention increases PrEP drug levels in a real-world setting. Presented at: Conference on Retroviruses and Opportunistic Infections; February 13-17, 2017; Boston, Massachusetts. Abstract 965

3. Golub SA, Gamarel KE, Lelutiu-Weinberger C. The importance of sexual history taking for PrEP comprehension among young people of color. AIDS Behav. 2017;21(5):1315-1324.

4. Parsons JT, Rendina H J, Lassiter JM, Whitfield, THF, Starks TJ,  Grov C. Uptake of HIV pre-exposure prophylaxis (PrEP) in a national cohort of gay and bisexual men in the United States. J Acquir Immune Defic Syndr. 2017;74(3): 285-292.