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High but variable STI rates in PrEP studies – Is PrEP the cause or a potential solution?

A new meta-analysis of 20 studies and roll-out projects of HIV pre-exposure prophylaxis (PrEP) in gay and bisexual men confirms very high rates of diagnosis of sexually transmitted infections (STIs) in study participants and PrEP takers.

Dr Ricardo Werner and colleagues from the Berlin Institute of Health analyse STI rates in the largest dataset of PrEP studies and rollout programmes so far. In their discussion section they also look at the evidence for and against PrEP having a causative role in STI increases, or whether these are driven more by other factors such as increased testing.

The meta-analysis finds that the rates of diagnosis for any STI in participants in the studies ranges from 33 to 100% – meaning, in the latter case, that there were more STI diagnoses over the course of a year than there were participants in the study. Thus, there is considerable heterogeneity in the STI incidence recorded by different studies. Some of the studies they refer to also show heterogeneity between individuals, with a minority of participants accounting for a majority of STI infections.

The authors add that the evidence for whether increases in STIs happen before or after PrEP initiation is very mixed, and suggests that at least some of the high rates of STIs seen in people taking PrEP is due to high rates of STI testing.

The authors conclude that the incidence rates of STIs among gay men who engage in high-risk behaviour are high and raise particular concerns with regard to gonorrhoea and hepatitis C. They add that “by offering access to structures that provide regular STI monitoring and prompt treatment, PrEP may not only decrease HIV incidence but also have beneficial effects in decreasing the burden of STIs.”

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 to 17 year olds (1.8%), but the highest rate was in its companion study in 18 to 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 to 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.

The meta-analysis and accompanying evidence shows that although STI rates are generally high in gay and bisexual men taking PrEP, there is a large variation between studies and the populations they involve, and some of the studies referenced in the discussion section find that STI infections are concentrated amongst a particularly at-risk minority.

The authors of the meta-analysis comment: “Despite the heterogeneity of some of our results, our overall findings suggest that the incidence rates of various STIs among gay and bisexual men who engage in high-risk sexual behaviour is high.” In other words, the kind of sex that exposes people to HIV unless they take PrEP also exposes them to the other STIs – and so, as the authors add, “This subgroup of men can benefit from access to STI testing and treatment at close intervals.”

They add: “The use of PrEP is a highly effective means of preventing HIV and should be embedded in a comprehensive programme targeting primary and secondary prevention and treatment of other STIs.”

Background: Men who have sex with men (MSM) and who engage in condomless anal intercourse with casual partners are at high risk of acquiring sexually transmitted infections (STIs), but reliable epidemiological data are scarce. Studies on HIV pre-exposure prophylaxis (PrEP) enrol MSM who indicate that they engage in behaviour that puts them at high risk of acquiring HIV. Because they also screen for STIs at regular intervals, these studies may serve as a valuable source to estimate incidence rates of STIs in this subpopulation of MSM.
Methods: We systematically searched for trials and observational studies of PrEP in MSM that reported data on the incidence of STIs during the study period. Incidence rates were calculated as events per 100 person-years (py) with 95% confidence intervals (CI). Data from individual studies were pooled building subgroups along study types and geography. We performed sensitivity analyses, including data only from studies that met pre-defined quality criteria.
Results: Twenty-four publications on 20 studies were included. The majority of studies reported that sexual behaviour and/or STI incidence remained stable or decreased during the study period. For syphilis, incidence rates ranged from 1.8/100py to 14.9/100py, the pooled estimate was 9.1/100py (95%-CI: 7.7–10.9). Incidence rates for gonorrhoea and chlamydia of any site ranged from 13.3/100py to 43.0/100py and 15.1/100py to 48.5/100py, respectively. Considering only studies that met the criteria for sensitivity analysis yielded pooled estimates of 39.6/100py (95%-CI: 32.9–47.6) and 41.8/100py (95%-CI: 33.9–51.5), respectively. The overall estimate for hepatitis C incidence was 1.3/100py (95%-CI: 1.0–1.8).
Conclusions: Despite partly heterogeneous results, the data depict high incidence rates of STIs among: MSM who engage in higher-risk sexual behaviours such as condomless sex with casual partners. This subpopulation of MSM requires access to STI screening at close intervals. By offering access to structures that provide regular STI monitoring and prompt treatment, PrEP may not only decrease HIV incidence but also have beneficial effects in decreasing the burden of STIs.

Ricardo Niklas Werner, Matthew Gaskins, Alexander Nast, Corinna Dressler

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[link url=""]PLOS One abstract[/link]

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