Rare HIV PrEP Failure Reported in San Francisco
A San Francisco man was apparently infected with partially resistant HIV despite consistent use of Truvada pre-exposure prophylaxis (PrEP), according to a poster presented at IDWeek 2018, held 5th October, 2018 San Francisco.
The patient was HIV-negative (by both rapid Ab and pooled HIV RNA) at 3, 6 and 10 months after PrEP initiation.
At month 12, he was diagnosed with and treated for urethral gonorrhea (GC); all other STD testing was negative.
At his month 13 PrEP visit, pt reported recent methamphetamine use and condomless receptive anal sex with a male partner, both for 1st time in > 1 year. Reported excellent PrEP adherence.
Rapid HIV Ab negative. PrEP prescription renewed. 5 days after this visit, HIV RNA returned at 559 copies/mL.
After a year on PrEP with apparently good adherence according to blood and hair sample tests, the young man was infected with an HIV strain that was resistant to emtricitabine, but still susceptible to tenofovir, reported Stephanie Cohen, MD, of the San Francisco Department of Public Health.
Drug level testing of plasma and dried blood spots showed adequate drug levels at the time of the visit and over the preceding six weeks. Unlike the recent North Carolina case, this man had longer hair that allowed drug level testing going back six months, which showed consistent good adherence to Truvada.
Genotypic and phenotypic testing showed that the man’s HIV was resistant to emtricitabine but remained susceptible to tenofovir. His virus carried the L74V, L100I, M184V and K103N mutations, but not the K65R tenofovir-resistance mutation. Further, the genetic diversity of his virus population suggested he had acute infection, probably acquired within the previous few weeks.
The man was immediately notified and started a complete antiretroviral treatment regimen containing tenofovir alafenamide or TAF (the newer kidney- and bone-friendly formulation of tenofovir), emtricitabine, dolutegravir (Tivicay) and ritonavir-boosted darunavir (Prezista).
In addition, one of the man’s sexual partners was found to be HIV positive with the same viral genotype and an HIV RNA level of 15,000 copies/ml, and he was re-linked to care. The fact that the partner’s virus had the same resistance pattern suggests transmission of resistant virus, rather than resistance newly emerging in the recently infected man.
This is the sixth known case of HIV infection despite a high level of adherence, the authors said in a poster presented at the annual IDWeek meeting, with joint sponsorship by the Infectious Diseases Society of America (IDSA), the HIV Medicine Association(HIVMA), the Society for Healthcare Epidemiology of America (SHEA), and the Pediatric Infectious Diseases Society (PIDS).
“We’ve always said that PrEP is not 100% efficacious,” Charlene Flash, MD, of Baylor College of Medicine in Houston, who was not involved with the case report, told MedPage Today. “So although it’s important for us to evaluate the parameters of what happened in each individual case, it’s an important reminder that PrEP is not a golden bullet. It’s just one element in our prevention toolkit.”
The FDA approved Truvada for HIV prevention in 2012 based on data from the iPrEx trial, which showed that once-daily Truvada reduced the risk of HIV infection by 92% among mostly gay and bisexual men with blood drug levels indicating consistent use. Across several other studies and demonstration projects, no one who took Truvada at least four times a week has become infected.
However, a handful of cases of apparent or confirmed PrEP failure in real-world use have been reported at scientific conferences and in the medical literature.
In 2016, clinicians in Toronto reported that a man who used PrEP consistently was infected with an HIV strain that was resistant to both tenofovir and emtricitabine.
A similar case was reported in New York City later that year. In 2017, researchers from Amsterdam reported the first case of PrEP breakthrough involving drug-susceptible HIV.
Another probable case from North Carolina was presented at a conference earlier this year. That case was the first to measure drug levels in hair samples to assess adherence over time. This technique showed that the man had adequate tenofovir levels during the three months prior to testing positive for HIV, but because he had short hair this was as far back as the tests could go.
Our biggest challenge in HIV prevention is not figuring out why in these extremely rare circumstances PrEP is ineffective, but rather how can we make sure those who can benefit from PrEP know about it? How can we make it as acceptable, accessible and affordable as possible? And how do we support individuals who choose to take PrEP so that they can stay on it throughout periods of risk?”
Sullivan P et al. Acquisition of TDF-susceptible HIV despite high level adherence to daily TDF/FTC PrEP as measured by dried blood spot (DBS) and segmental hair analysis: a case report. IDWeek, abstract 1298, 2018.