The new case
involves a 21-year-old Latino man who reported having sex with men,
transgender women and cisgender (non-trans) women. He started taking daily PrEP
at San Francisco’s main sexually transmitted infection clinic. At that time he
tested negative for HIV antibodies and HIV RNA.

The man was
prescribed a 30-day supply of Truvada
with two refills and asked to return in three months for follow-up monitoring.
He again tested HIV negative at three, six and 10 months after PrEP initiation.

At his
13-month visit, the man said he had recently used methamphetamine
and had condomless receptive anal sex, but he reported excellent PrEP
adherence. A rapid HIV antibody test was negative and his PrEP prescription was
renewed. But five days later his HIV RNA test came back positive, with a viral
load of 559 copies/ml.

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.

Because the man started treatment so early, and because he
was taking Truvada at the time of
infection, this case could be interesting in terms of HIV cure research,
similar to another recent San Francisco case in
which a man with very recent HIV infection started Truvada for PrEP. When this was discovered he stepped up to a
complete antiretroviral regimen. After three years on treatment with no detectable
HIV in his
blood, lymph nodes, gut or bone marrow, he tried a closely monitored treatment
interruption, remaining undetectable for about seven months before viral
rebound occurred.

Based on these findings, the researchers concluded that HIV
acquisition can occur in a person taking Truvada-based
PrEP in the setting of emtricitabine resistance, even when adherence is high
and the virus is susceptible to tenofovir.

“Individuals taking PrEP and health care providers
should be aware that PrEP failure is very rare, but not impossible, even with
consistent adherence,” they wrote.

“I
really want to say that PrEP is almost there in terms of 100% [protection].
This is a rare case and I don’t want anyone to worry too much. It’s 99%, and
that’s pretty good for a medical intervention,” Monica Gandhi of UCSF, the
team’s lead author, told aidsmap.com.

Grant went
further, questioning the emphasis on these rare cases.

“The
latest report is like others. The infection was detected early when the viral
load was still low and the immune system was still preserved. PrEP was
intensified to add an additional medicine. Viral load was rapidly suppressed,”
he said. “Almost all people who use PrEP stay free of HIV and a handful of
others are diagnosed early and promptly and successfully treated. Once virally
suppressed on treatment, their infection is non-transmissible. These cases call
us to reconsider our stigmatizing way of regarding people with HIV. Why is this news? The story is that in 2018,
humanity continues to suffer from a plague of our own making: the plague of
stigma.”