Incidence of HIV in a Nationwide Cohort Receiving Pre-Exposure Prophylaxis for HIV Prevention

Puja Van Epps, MD; Brigid M. Wilson, PhD; Will Garner, MD; Lauren A. Beste, MD; Marissa M. Maier, MD; Michael E. Ohl, MD


J Acquir Immune Defic Syndr. 2019;82(5):427-430. 

In This Article

Abstract and Introduction


Background: Cases of HIV, while infrequent, have been reported during tenofovir disoproxil fumarate/emtricitabine use as pre-exposure prophylaxis (PrEP). We describe the incidence of HIV and patterns of PrEP use within the Veterans Health Administration (VHA).

Methods: We conducted a retrospective cohort study among persons initiating PrEP in the VHA between July 2012 and April 2016 using national VHA data. We defined time on PrEP and time at risk of HIV exposure as the total time from the first PrEP fill to exhaustion of supply of the final PrEP prescription. We identified incident cases of HIV infection after PrEP initiation based on laboratory data. Medication adherence measures and days without pills were calculated using pharmacy fill data. We used a chart review to determine patient-reported PrEP use around the time of diagnosis.

Results: We identified 825 unique patients initiating PrEP; they were 97% men and 67% white, with a mean age of 41 years. Six HIV infections were observed during the study period, yielding an HIV incidence of 0.8 (Poisson exact 95% confidence interval: 0.3 to 1.8) cases per 100 person-years. Two cases occurred during active PrEP use by self-report and perfect adherence based on fill data. Both were infected with viruses containing the M184V mutation. Four additional cases were diagnosed after self-reported discontinuation.

Conclusions: HIV infection was rare in a nationwide cohort of PrEP users. Although most of the infections occurred during inconsistent PrEP use, infections during periods of high measured adherence were also observed. These findings highlight the importance of PrEP persistence during periods of risk.


In 2012, the United States Food and Drug Administration approved once-daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk persons.[1–3] PrEP is estimated to be up to 92% effective in preventing sexual transmission and up to 73% effective in preventing transmission through injection drug use.[4] Although rare, HIV acquisition has been described during PrEP use, especially in settings of low adherence. Clinical trials have reported HIV cases during PrEP use; for example, the iPrEx study reported 36 infections in the TDF/FTC group with 8 cases occurring during periods of high adherence (>90%).[3] Emergent HIV infections have also been reported in open-label PrEP studies and demonstration projects with HIV incidence ranging from 0.19 to 1.8 per 100 person-years.[5–7] HIV incidence as high as 3.39 per 100 person-years has been reported in a demonstration project involving young men who have sex with men.[8] Meanwhile, the Kaiser Permanente Northern California health care system has reported no infections during 5104 person-year of PrEP use.[9] HIV incidence has varied in these cohorts that have largely focused on metropolitan areas.

The Veterans Health Administration (VHA) is the largest health care system in the United States and maintains an integrated electronic medical record that permits evaluation of national cohorts of PrEP users. We have previously described adherence and access to PrEP use in the VHA,[10,11] but to the best of our knowledge, HIV incidence in a nationwide diverse cohort has not been reported. VHA serves a population that is older and more geographically dispersed than other PrEP cohorts. This provides an opportunity to describe experience with PrEP in a varied national cohort. In this study, we report the incidence of HIV infection among PrEP users in VHA and describe the relationships between patterns of PrEP medication use and incidence of HIV cases, as well as describe viral resistance patterns among PrEP recipients who acquired HIV.