Case Study Finds Incidence of HIV Despite Use of PrEP

Although preexposure prophylaxis (PrEP) has achieved significant results in reducing the incidence of HIV in regions where it has been made available and implemented, it is not infallible. As a case report published February 2nd in The New England Journal of Medicine (NEJM) notes, “incident HIV is possible despite adherence to preexposure prophylaxis when persons are exposed to [regimen]-resistant virus.”

Because of their findings in a 43-year-old male treated with PrEP, the authors of the report—a team of physicians, pharmacists, and basic researchers from Maple Leaf Medical Clinic and St. Michael’s Hospital in Toronto; the University of Colorado Anschutz Medical Campus in Aurora, Colo.; and the British Columbia Centre for Excellence in HIV/AIDS in Vancouver—recommended that clinicians prescribing the regimen, which consists of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), urge enhanced surveillance for mutant HIV strains that may compromise PrEP’s effectiveness. They also call for increased patient education with regard to the importance of regimen adherence in efficacy.

PrEP, otherwise known as FTC/TDF (Truvada, Gilead), was approved by the US Food and Drug Administration in 2012 for HIV preexposure prophylaxis. Notably, the iPrEx study, published in December 2010, found that the regimen, when administered to HIV-negative men who have sex with men, reduced the incidence of infection by 44%. A follow-up study, published in July 2014, demonstrated that adherence to the prescribed regimen was vital to its efficacy, as is the case with most antiviral therapies.

Now the NEJM case report calls this into question.

Indeed, the 43-year-old male in the case, from Toronto, who indicated to his physicians that he had sex with men, thus making him at high-risk for HIV and a prime candidate for PrEP, was started on oral daily FTC/TDF in April 2013, 9 weeks after a negative HIV test and following a period of 3 months during which he abstained from sex. He underwent 7 HIV screening tests over the ensuing 21 months and, based on pharmacy dispensation records, he adhered “perfect[ly]” to the regimen for a period of 24 months.

At 24 months, the patient tested positive for HIV-1. He did not experience the “classic symptoms of acute HIV seroconversion,” but did report “epigastric discomfort,” along with an elevated body temperature.

The authors performed liquid chromatographic-tandem mass spectrometric analysis of a plasma sample from the patient, which revealed a tenofovir concentration of 152 ng/mL, which is considered “consistent with recent administration of the drug.” Further analysis found tenofovir concentration levels “consistent with long-term adherence.”

Believing that the test findings were a “false positive,” citing his sexual abstinence and treatment adherence, the patient refused to discontinue PrEP until his diagnosis could be confirmed. He was started on a regimen of darunavir 600mg twice daily, ritonavir 100mg twice daily, and raltegravir 400mg twice “due to concern about emergent HIV drug resistance.” On day 7, his CD4 count was 710 cells/mm³ and HIV viral load was 28,000 copies/mL (4.45 log¹⁰ copies/mL). After 21 days of combination therapy, the viral load became undetectable.

Subsequent genotypic and phenotypic testing of a sample of the patient’s blood revealed multidrug resistance, and showed presence of the M184V mutation, which has been shown to compromise (FTC) activity, as well as “several thymidine analogue mutations, revertant substitutions, or both,” which have been shown to “slightly decrease TDF susceptibility.”

The authors of the case report did not respond to requests for comment. However, they noted in the case report that these viral mutations “probably explain [the] failure of preexposure prophylaxis. The multiple thymidine analogue mutations detected are unlikely to have been selected in the short duration of drug exposure; this suggests that resistance was transmitted rather than acquired after drug exposure.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.