Werner and colleagues analysed STI rates in 24 papers
concerning 20 different studies of PrEP in gay and bisexual men. These studies
included randomised controlled studies such as iPrEx, PROUD and Ipergay and
their open-label extensions, as well as studies targeting particular populations
such as the PrEPare study for teenagers. They
also included country-specific demonstration studies such as PrEP Brasil,
AmPrEP in the Netherlands and the Australian demo projects, and also PrEP
rollout programmes such as the Kaiser Permanente PrEP rollout in northern
California and Prévenir in France.

A total of 11,918 gay and bisexual men were included and the
data included about the same number of person-years of follow-up (11,686).

The annual diagnosis rates for any STI ranged, as mentioned above, from 33% to 100%, with the average diagnosis rate among the highest-quality
studies being 84%.

Of the three most common bacterial STIs (syphilis, gonorrhoea
and chlamydia), syphilis in the one where increased STI testing may have the
smallest impact on diagnoses. This is because it can be picked up in a blood
test and is therefore already tested for more consistently; in contrast, gonorrhoea
and chlamydia diagnoses are often dependent on rectal and throat swabs that are
less consistently performed, at
least in some countries
.

The average diagnosis rate of syphilis in PrEP-takers in
this meta-analysis was 9.2% overall and 9.5% in the highest-quality studies.

These rates are obviously much higher than in the general
population, where only one in 10,000 people a year (0.0097%) is diagnosed with
syphilis. But, while higher, it is not of a different order of magnitude than
the rate seen in gay and bisexual men attending STI clinics, which in London in
2016 was 4.4%.

Bacterial STIs have a specific age profile in both men and
women, with low rates seen in very young people just starting sex, but the
highest rates in people in their late teens and twenties, when they are most
sexually active. In this meta-analysis the lowest rate of syphilis was in a
study in 15-17-year olds
(1.8%), but the highest rate was in its
companion study in 18-22-year olds
(15%).

The rate of gonorrhoea varied from 12% to 43%, with an
average rate of 27% and a rate in the most rigorously controlled and largest studies
of 40%.

Chlamydia was diagnosed at very similar rates: the range was
14%-48% in different studies, with an average rate of 30%, and 42% in the most
rigorously controlled and largest studies.

One reason the larger studies had higher rates is because
STI rates tended to be higher in the cohort studies and rollout programmes than
they were in the earlier randomised controlled studies, where people didn’t
necessarily know they were on PrEP and which were done at a time when STI rates
were somewhat lower.

Gonorrhoea and chlamydia were also classified by body site. In
the most rigorous analysis, 4% had urethral gonorrhoea and 9% urethral
chlamydia; rectal infections were more common, with rates of 17% and 33%
respectively for rectal infections.

Five studies reported on the incidence of hepatitis C. This
ranged from zero to 1.9%,  with an
average annual rate of 1.3%. This is very high, given that annual
hepatitis C incidence in HIV-positive gay men is only 0.78% and in HIV-negative
men in general is only 0.04%.

There is thus no doubt that there are high rates of STIs in
people taking PrEP. However the evidence as to whether PrEP leads to people acquiring more STIs is
much more ambiguous. In particular, the picture is confounded by the fact that PrEP leads to people taking
STI tests and getting diagnosed and treated more often.

In their discussion section, the authors summarise this
evidence briefly: the following section elaborates on this, adding in findings
from some of the studies they reference.