Transmitted drug resistance: The other side to the PrEP failure case we’re not talking about
Much of the media coverage thus far about the person who HIV seroconverted while on (and adherent) to PrEP has focused on the side of the story that’s been documented—the target case’s own story of consistent adherence to Truvada, exposure to HIV and resulting seroconversion. But what about the other side of the story, of the person who unwittingly transmitted multi-drug resistant HIV?
“It’s not uncommon for people to acquire a drug resistant strain of HIV from a partner, but transmission of multi-drug resistant HIV is very rare,” said Hyman Scott, MD, from the University of California San Francisco, who explained that this is what makes this case so compelling—and a major concern.
Read more about the difference between acquired and transmitted drug resistance.
In the U.S., it is estimated that almost 20%, or 1 in 5, newly-diagnosed men who have sex with men (MSM) have transmitted drug resistance to one or more classes of HIV drugs. A large surveillance project by the Centers for Disease Control and Prevention (CDC) found that about 10% of HIV-positive MSM who had not yet taken antiretrovirals were resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI), 7% to a nucleoside reverse transcriptase inhibitor (NRTI), and 6% to a protease inhibitor.
But the surveillance study found that transmission of multi-drug resistant virus is rare. Less than 1% (0.4%) of people had drug resistant mutations to all three classes of HIV drugs, while just over 2% had resistance to 2 classes of drugs and 16% were resistant to only one.
The man who acquired HIV on PrEP stands out because he acquired HIV with drug resistant mutations to three classes of HIV medications. In addition to being resistant or having a reduced response to NRTIs including lamivudine, emtricitabine, abacavir and tenofovir and the NNRTI nevirapine, he also showed resistance or reduced response to newer drugs—the integrase strand transfer inhibitors (INSTIs) elvitegravir, dolutegravir and raltegravir.
David Knox, MD, the clinician who presented the PrEP failure case at CROI 2016, speculated that the person who transmitted this multi-class drug resistant strain of HIV may have been failing a commonly prescribed four-drug combination pill.
“Overall, our patient’s profile suggests that he was exposed to somebody who was failing a regimen of TDF/FTC/elvitegravir/cobicistat, or Stribild,” said Knox.
People who develop drug resistance (acquired resistance) do so in response to selection pressure from partial adherence to HIV medications. Resistance to only one class of drug is more common because resistance happens slowly—usually one mutation at a time.
“The general belief is that switching [medications] quickly after detection of the first drug-resistance mutation can prevent the accumulation of further drug-resistance mutations,” explained Pleuni Pennings, from Stanford University, in an Infectious Disease Reports article. In other words, if you catch a resistance mutation early—and switch medications to a more effective regimen—you won’t provide an opportunity for additional resistant mutations to develop.
But, if a person continues the same treatment, even if one of the drugs no longer works to suppress HIV replication, the virus will likely develop resistance to the other drugs in that regimen.
It’s possible that the man who transmitted HIV in this instance was on, and failing, Stribild, as Knox suggested. It’s also possible that he himself had been infected by another partner—and was entirely unaware of his infection.
“The suggestion that the person was failing Stribild was not confirmed in any published reports. There is a chance he was unaware of his infection, since this drug resistant strain can clearly be transmitted,” explained Scott.
Details of the situation presented in a Q&A in POZ seem to support this explanation.
“We met on bbrt [a bareback community], and he says he’s negative. I prefer to be with people who are positive and know it and are on meds—I’m on PrEP, you’re undetectable, the chances of transmission are like negative 10 percent—but I broke my rule with this guy.”
After reaching out after his diagnoses to give his partner a heads up that he should visit a doctor, he heard back, “I’m not worried, I’m OK.,” “I’m really busy and haven’t had a chance,” and “I’m out of town on work,” until finally the man stopped responding.
HIV experts hope that the man was able to contact his doctor, get tested—if undiagnosed—or get back into care if he did know he was positive. This is the other side of the story and it represents a big issue in the HIV care and prevention world. We have at our disposal tools such as PrEP and treatment as prevention that could work in tandem to end the epidemic, but systems of care that allow people to slip from their reach prevent us from harnessing their full power.
Read about one strategy to help people living with HIV get—and stay—in care made available by the Health Navigation program at San Francisco AIDS Foundation. Get additional information about PrEP and other HIV services at Strut, the new health and wellness center for gay, bisexual and transgender men in San Francisco.
Banez Ocfemia, M. C. and others. Epidemiology of HIV-1 transmitted drug resistance among men who have sex with men in 8 U.S. jurisdictions. XXIV HIV Drug Resistance Workshop, February 2015.
Knox, D. and others. HIV-1 infection with multiclass resistance despite preexposure prophylaxis (PrEP). CROI, 2016. Abstract 169aLB.
Pennings, P. S. HIV drug resistance: Problems and perspectives. Infectious Disease Reports, June 2013.
Straube, T. Meet the man who got HIV while on daily PrEP. POZ, March 2016.
Technical and scientific review by Hyman Scott, MD.