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.