By Benjamin Ryan
For the sixth time, researchers have documented a case of a man who has sex with men (MSM) contracting HIV while, according to multiple sources of evidence, he was adhering well to the daily regimen of Truvada (tenofovir disoproxil fumarate/emtricitabine) as pre-exposure prophylaxis (PrEP) against the virus. Given PrEP’s increasingly wide use around the world—an estimated 180,000 people, the vast majority of whom are MSM, are using it in the United States alone—the fact that so few PrEP-failure cases have reported to date helps back the scientific community’s adamant assertion that such cases will in all likelihood remain rare.
Case in point: A recent analysis conducted in King County, Washington, which includes Seattle and that recently saw a case of PrEP failure, indicated that transmissible HIV that is resistant to both of the drugs included in Truvada, emtricitabine and tenofovir disoproxil fumarate (TDF), is itself rare.
However, the strain of HIV that the man in the new case report contracted only had mutations associated with resistance to emtricitabine; his virus demonstrated susceptibility to TDF. His is the third documented case of an individual contracting a strain of a TDF-susceptible strain of HIV while, according to multiple sources of evidence, adhering well to the daily PrEP regimen.
The first reported case of PrEP failure, described in February 2016 at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, involved a Canadian MSM who was apparently taking Truvada routinely and who contracted a strain of HIV that was highly resistant to emtricitabine and showed reduced susceptibility to TDF. Since that time, five other cases, including this new one, have been reported at scientific conferences or elsewhere.
Presenting their findings at the IDWeek conference in San Francisco, researchers provided a case report of a 21-year-old Latino man who has sex with men, cisgender women and transgender women who started daily PrEP through a municipal sexually transmitted infection (STI) clinic. He was prescribed 30 days of Truvada with two refills, with instructions to return for monitoring every three months.
Rapid HIV antibody tests as well as pooled viral RNA tests (which look for presence of the virus) indicated the man was HIV negative upon his first assessment for PrEP as well as at three, six and 10 months after starting Truvada for HIV prevention. Between starting PrEP and acquiring HIV, he was diagnosed with urethral chlamydia once and urethral gonorrhea three times.
At his clinic visit 13 months after starting PrEP, the man reported recently taking crystal meth and engaging in condomless receptive anal sex with a male partner. He said that he had not taken meth nor had he engaged in this type of sex for more than one year prior. He reported excellent adherence to the daily Truvada regimen at this time. A test conducted on a sample he gave at this visit indicated he was negative for HIV antibodies.
However, five days after that 13-month clinic visit, the result of his HIV RNA test came back indicating that he had a viral load of 559.
The man was quickly notified that he had a detectable HIV viral load. He was quickly linked to care for the virus and put on Truvada plus Tivicay (dolutegravir) and Norvir (ritonavir)-boosted Prezista (darunavir) as antiretroviral treatment for the virus. At the visit when he was prescribed this treatment regimen, he had a viral load of 1,544 according to RNA testing; he also tested positive for HIV antibodies at that time, indicating he was officially HIV positive.
The man reported four recent sex partners, one of whom was a man living with diagnosed HIV who was not in medical care for the virus.
Researchers conducted genetic testing, specifically genotyping and phenotyping testing, of the HIV in the plasma sample the man in the case report gave that yielded the first positive viral load result as well as a sample taken the day he started HIV treatment. The scientists also conducted genetic testing known as single-genome sequencing on HIV’s genetic material encoded into human cells, called proviral DNA, analyzing a sample taken seven days after the man started treatment for the virus.
Tests indicated that the man had contracted HIV with the resistance mutations known as L74V, L100I, M184V and K103N. M184V in particular is associated with resistance to emtricitabine. Four of the five other documented cases of PrEP failure have involved a man contracting HIV with the M184V mutation; three of those cases also involved virus that harbored either of two specific mutations, called K70R and K65R, that cause reduced susceptibility to TDF.
The tests conducted for the new case report indicated that this particular man’s virus was indeed susceptible to the TDF. In other words, one, but not both of the drugs in Truvada was likely effective against the strain of HIV that this man contracted while taking PrEP regularly.
The single-genome sequencing indicated the man likely contracted HIV during the previous few weeks.
As for the HIV-positive partner whom the man indicated as a possible source of his infection, that man’s virus had the same viral genotype and the same viral mutations, indicating he was indeed the likely source. Such a finding also indicated that the man in the case report likely did not develop drug resistance to the components of Truvada while on PrEP. His HIV-diagnosed sexual partner, about whom there was no evidence in HIV surveillance databases indicating he had ever had a fully suppressed viral load thanks to antiretroviral treatment, was linked to medical care of the virus. At this man’s first medical appointment, he had a viral load of 15,000, which is well above the threshold (of approximately 1,500) generally considered necessary to render an individual living with the virus infectious through sex.
To help determine if the man on PrEP had indeed been adherent to his daily Truvada regimen as he asserted, the investigators took hair samples the day he started HIV treatment, conducted dried blood spot testing based on a sample taken two days later and also looked at a stored plasma sample from the 10-month visit. The hair sample indicated consistent Truvada use during the preceding six months. The dried blood spots indicated that during the preceding six weeks, the man had taken at least four doses of Truvada weekly—the minimum researchers estimate is needed for maximum protection against HIV among MSM. The plasma sample indicated that the man did not have HIV 10 months after starting PrEP and that he had recently taken a Truvada dose prior to giving the sample.
“Individuals taking PrEP and health care providers,” the case report authors concluded, “should be aware that PrEP failure is very rare, but not impossible, even with consistent adherence.”
To read the conference abstract, click here.
For a complete archive of nearly 300 PrEP-related articles, go to benryan.net/prep.