CROI 2017: STI Rates Among PrEP Users Are High, But Evidence that PrEP Increases Them Is Inconclusive

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A study of pre-exposure prophylaxis (PrEP) users presented at the Conference on Retroviruses and Opportunistic Infections this month in Seattle showed that they had very high rates of sexually transmitted infection (STI) diagnosis -- on the order of 20 times higher than among HIV-negative gay men in the general population. However, it is unclear whether STIs increased further after people went on PrEP.

[Produced in collaboration with aidsmap.com]

Researchers also saw an increase in STI diagnoses from a time point a year before people sought PrEP to the date they started it. And the percentage of men reporting never using condoms for anal sex somewhat increased while they were on PrEP, though it never exceeded 10% of all PrEP users.

The evidence that STIs increased further while people were on PrEP was, however, a lot more ambiguous. Chlamydia cases increased from the time of PrEP initiation to 9 months after starting it. On the other hand, syphilis diagnoses fell over the same time period, while gonorrhea diagnoses stayed at the same level. The only STI that increased during PrEP use was urethral gonorrhea, but that was only seen in a small number of individuals.

In a symposium, Matthew Golden, who runs the STI and HIV program in King County, which includes Seattle, told conference attendees that some other studies, such as an analysis of the Kaiser Permanente PrEP program in Northern California, showed that STI rates increased after PrEP was started. Others, such as the U.K. PROUD study, provided little evidence of this.

The problem in proving that PrEP has any causal relationship to STIs is that STIs among gay men were, in general, rising well before the advent of PrEP, and also that PrEP usually involves regular testing for HIV and STIs. Since many STIs are asymptomatic and self-limiting, more tests will result in more diagnoses.

The Study

To investigate the relationship between PrEP use and STIs, Golden and colleagues looked at condom use and STI diagnoses among gay men enrolling in the King County program between September 2014 and June 2016. He looked at condom use reported by participants at the time they started PrEP and at 3, 6, and 9 months after initiation. For STIs, he looked at the proportion of people who had STI diagnoses 1 year before they started PrEP, at the time they started PrEP, and during the time they were on PrEP.

The criteria for starting PrEP in the program were being a man (including transgender) or transgender woman who has sex with men and who reported rectal gonorrhea, early syphilis, use of methamphetamine or nitrites (poppers), or sex work in the year before asking for PrEP. Alternatively, they could have an HIV-positive partner who was not on antiretroviral treatment, not virally suppressed, or within their first 8 months of viral suppression. Although these criteria could have included heterosexuals, in practice all individuals in the cohort were men who have sex with men.

A total of 218 men started PrEP and completed baseline behavioral questionnaires, but only 108 completed follow-up to 9 months. This was a young cohort on average (average age 30.6) and race/ethnicity reflected the racial makeup of Washington State: 53% were white, 22% Hispanic, 10% Asian or Pacific Islander, 9% African American, 2% Native American, and 4% other ethnicity.

The proportion of men saying they never used condoms for anal sex was higher among men on PrEP than before they started, though there was no evidence for an increase during time on PrEP. The increases were relatively slight and largely in single percentages, but were statistically significant. The proportion saying they had never used condoms during the previous 3 months was 6% at baseline and 10% at 3 months after starting PrEP, though it declined to 8% at 9 months.

The proportion of men saying specifically that they never used condoms for receptive anal sex was 2% at baseline and 4% while on PrEP for those with HIV-positive partners, and 4% at baseline and 8% while on PrEP for those with HIV-negative partners.

There was also an increase in never using condoms for insertive sex with HIV-positive partners, from 2% at baseline to 6% while on PrEP. Condom use did not change significantly with partners of unknown HIV status.

STI diagnoses increased significantly from a year before starting PrEP to the time PrEP was started. In the 3 months ending a year before PrEP initiation, 6.5% of participants were diagnosed with chlamydia, 10.2% with gonorrhea, and also 10.2% with early or early-latent syphilis. When tested at the start of PrEP, the proportion diagnosed with chlamydia was 16%, nearly 3 times the rate, and 20.4% with gonorrhea, twice the rate. Syphilis increased slightly to 12%. Rectal chlamydia increased from 4.6% to 14.8% and rectal gonorrhea increased from 9.3% to 13.9%.

All this may show, however, is that people at high risk for STIs tend to seek PrEP, and that comprehensive testing picks up more STIs than ad hoc testing.

The evidence that STIs increased during PrEP use is more ambiguous. Chlamydia, and particularly rectal chlamydia, diagnoses did increase further, from 16% to 22%, and from 15% to 19%, respectively.

On the other hand, diagnoses of gonorrhea and rectal gonorrhea stayed at the same rate of around 20% and around 14%, respectively. And early and early-latent syphilis decreased, from 12% to 7%.

It may be relevant that diagnoses of chlamydia -- the STI most likely to be asymptomatic -- increased the most. So Golden and colleagues picked out 2 STIs that were generally not asymptomatic in order to try and factor out increases due to the detection of asymptomatic cases.

The results were contradictory. The proportion of men diagnosed with urethral gonorrhea -- which is nearly always symptomatic -- increased from 0.9% at baseline to 5.6% while on PrEP. One the other hand, diagnoses of primary and secondary syphilis, excluding early latent syphilis, i.e., only stage of syphilis in which symptoms are usually seen, declined both before and while on PrEP, from 9.3% a year before baseline, to 7.4% at baseline, to 3.7% while on PrEP.

It is very difficult to make any generalizations from these figures. The increase in urethral gonorrhea is suggestive, but this was only a small study where the 0.9% of men with urethral gonorrhea at PrEP initiation represents 2 individuals and the 5.6% at 9 months represents 6 people.

The STI rates in PrEP users were certainly high: rates of all 3 STIs were almost exactly 20 times what they were in the general HIV-negative gay population, and rectal STIs were 30 times more common -- for instance, the general gay-population diagnosis rate of rectal gonorrhea was 0.9%, versus 26% among PrEP users.

STI Rates Should Fall with Widespread PrEP Coverage

A mathematical modeling study by Samuel Jenness from Emory University and colleagues,also presented at CROI, found that if PrEP became widespread among gay men in the U.S., STI diagnoses would rise in the first year, but would fall thereafter. If the testing interval was once every 6 months, for instance, all-STI incidence among gay men would fall from about 5.4% a year after starting a PrEP program to 4% at 3 years after starting it and less than 2% at 10 years after starting.

This was based on an assumption of high coverage -- that 40% of gay men take PrEP -- and as long as every STI gets treated. STI incidence would remain unchanged rather than fall if only 50% got treated. However, these net benefits of PrEP are calculated on the basis of condom use among gay men on PrEP falling by 40% -- they would be even greater if condom use did not fall.

There was no support for the hypothesis that PrEP could cause STI increases by themselves. In this model, even zero condom use while on PrEP could not transform the STI rates seen in the general gay population into the ones seen in PrEP users. This backs up the idea that people seeking PrEP already know they are at high risk and don’t think that risk will change by itself.

2/27/17

Sources

MA Montano, JC Dombrowski, LA Barbee, M Golden, et al. Changes in sexual behaviour and STI diagnoses among MSM using PrEP in Seattle, WA. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 979.

S Jenness, K Weiss, SM Goodreau, et al. STI incidence among MSM following HIV preexposure prophylaxis: a modeling study. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 1034.