What happened here? This is the first case that offers
evidence that appears to show that on rare occasions PrEP may not work against
non-drug resistant HIV. Aidsmap.com talked to Dr Elske Hoornenborg, who leads AMPrEP,
and Dr Godelieve de Bree, who works at the Amsterdam Academic Medical Centre
and is involved in the man's HIV care.
It is possible that the man had a lapse in PrEP use immediately
after his six-month visit that did not show up in the eight-month dried blood
spot test, but he maintains he had full adherence and there is absolutely no
sign of any lapse.
A clue may lie in the fact that the man had a lot of
high-risk sex, even for someone enrolling in a PrEP trial. During his first
seven months in the study he averaged 56 anal sex partners per month and about
30 episodes of condomless sex a month. He averaged 16 days per month when he
did have condomless sex and on those days averaged 3.7 partners.
“This PrEP user came to the study saying he had no doubt he
would acquire HIV unless he went on PrEP,” said Dr Hoornenborg. “He was highly
educated and knew exactly what the risks were but did not feel he was able to
change his sexual risk pattern, so took action by applying for the study.”
He did have ‘chemsex’ and took mephedrone, GHB/GBL, ketamine,
cocaine and amphetamine, and admitted to injecting ketamine twice but insisted
he used sterile needles. He had two episodes of rectal gonorrhoea and one of
rectal chlamydia in his first seven months on PrEP. He did not contract hepatitis C and
was vaccinated against hepatitis B.
Dr de Bree has a hypothesis. “This is speculative,” she says,
“but oral PrEP works by stopping HIV getting into the bloodstream and reaching
the lymph nodes.”
“Short-lived infections may be happening within the cells of
the gut mucosa which can even stimulate an immune response but which never get
any further because the PrEP stops them at that point. It is perhaps just a
matter of statistics that very occasionally, one infection slips through.”
She added that some people have considerably lower levels
of emtricitabine (FTC) in their gut tissues than they do in their blood, which
could affect PrEP efficacy. Something might have happened in this person that
affected their tissue levels of PrEP temporarily.
There are mysteries to this case, however. The lack of HIV
antigens and viral load in the first few weeks after infection can be explained
by the individual being on PrEP, which would tend to suppress HIV replication even
if it did not suppress infection. The lack of resistance also suggests that PrEP suppressed HIV before it could reach the levels at which
resistance would have developed. Drug resistance would develop after infection if viral replication was not suppressed.
But in that case, how did the man develop antibodies to
HIV? Antibodies only develop if HIV antigens are stimulating the immune system somewhere,
and are sometimes lost, or never develop, in studies where people are treated
extremely early. There must have been a point after infection at which HIV antigens were circulating
at high enough levels to generate antibodies. It can be hypothesised that local
priming with HIV in the gut (which is an area rich in lymphocytes) has led to
the development of antibodies. There are people who have been exposed to HIV who,
although remaining uninfected, develop an HIV-specific immune response.
The seroconversion illness symptoms are atypical too; difficulty
with urination is not a common symptom and suggests very localised inflammation
in the genital tract or prostate. This could also suggest an aberrant immune
response that may have facilitated HIV infection, though all this is
Whatever the mechanisms, this case does look like the first
case of infection with non-resistant HIV despite consistent adherence to PrEP.