Participants taking tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis (PrEP) continued to have high rates of sexually transmitted infections (STIs) in two US PrEP demonstration projects, according to a pair of reports at the Conference on Retroviruses and Opportunistic Infections (CROI 2016) last month in Boston. Semi-annual STI testing missed many cases, leading researchers to suggest that gay men on PrEP could benefit from screening every three months.
One of the most common concerns surrounding PrEP is the high rate of STIs seen among users. There is little evidence that PrEP actually causes an increase in STIs, but gay and bisexual men at risk for HIV already have high STI rates, and many PrEP users are likely to be already having, or wish to have, sex without condoms.
As Sheena McCormack, lead investigator for the English PROUD study, explained at a CROI symposium on innovations in PrEP, "the pre-existing trajectory of rising STIs [among men who have sex with men] is carrying on, but PrEP means HIV doesn't have to rise too."
On the other hand, the regular STI screening recommended for people on PrEP encourages prompt diagnosis and treatment, which reduces onward transmission and could potentially contribute to lowering STI rates among PrEP users compared to non-users.
Scheduled screening of at-risk asymptomatic individuals is important because some STIs do not cause symptoms and can be transmitted by people who are unaware they are infected and show no visible signs such as sores or discharge.
The US Centers for Disease Control and Prevention (CDC) PrEP guidelines recommend STI testing at least every six months for asymptomatic individuals, though PrEP users should be seen every three months for HIV testing and Truvada prescription renewal, and some clinics do screen for STIs at every visit. CDC's 2015 sexually transmitted disease treatment guidelines recommend screening every three to six months for men who have sex with men (MSM), especially those with a past history of STIs. The British Association for Sexual Health and HIV recommends that all sexually active MSM should be tested for STIs at least annually, with those at high risk being tested every three months.
SPARK PrEP project
Sarit Golub of Hunter College presented findings from the SPARK community-based PrEP demonstration project at Callen-Lorde Community Health Center in New York City. SPARK participants receive syphilis and urethral and rectal chlamydia and gonorrhoea tests every three months, but are asked to come to the clinic between scheduled visits if they experience STI symptoms.
Dr Golub's team analysed medical records data from 280 SPARK participants for the six months prior to starting and through the first year on PrEP. The researchers did not report a demographic breakdown, but Callen-Lorde is an LGBT health centre so presumably most were gay and bisexual men.
They found that 13% of SPARK PrEP clients had an STI at six months before starting PrEP and 11% tested positive for an STI at their PrEP prescription visit.
At the three-month follow-up visit after starting PrEP, 13% were diagnosed with an STI. More than three-quarters (77%) of these did not have symptoms and two-thirds did not have a prior STI history that would have triggered screening if it were not done on a schedule.
Subsequently, 21% of participants at the six-month follow-up visit, 15% at the nine-month visit and 13% at the 12-month visit were diagnosed with STIs, with most (83%, 68% and 77%, respectively) being diagnosed thanks to routine screening rather than testing triggered by symptoms. Dr Golub noted that STI diagnoses rose a bit at six months and then reverted to around the previous level by month 12.
A majority of these diagnoses, ranging from 71 to 100% at the various visits, were rectal chlamydia or gonorrhoea – which are more likely to be asymptomatic – while 16 to 43% were urethral infections and 0 to 12% were cases of syphilis.
Among participants with 12 months worth of complete follow-up data, 43% (55 out of 128) were diagnosed with at least one STI after starting PrEP. The number with repeat diagnoses rose over time, from about a quarter at the first PrEP prescription visit to three-quarters at the 12-month follow-up visit. Screening based on prior diagnosis alone would have missed 66% of cases at three months and 16% at nine months.
"Current CDC guidelines may miss a significant number of asymptomatic STIs among PrEP users," the researchers concluded. They suggested that STI screening may be particularly important at the first three-month follow-up visit, and said that routine STI testing at each three-monthly PrEP prescription visit "appears warranted", especially for those with a past history of STIs.
"Folks who are deciding to take PrEP need it – if there is an increase in STIs, it is outweighed by HIV protection," Dr Golub said at a CROI press conference. Given that PrEP is starting to roll out widely, she said, "we need to change these guidelines now, because it is much harder to tell providers to change their practices once they’ve started."
US PrEP Demo Project
In a related study Stephanie Cohen of the San Francisco Department of Public Health presented findings on STI rates among participants in the US PrEP Demo Project, and the proportion of infections for which diagnosis would have been missed and treatment delayed with less frequent screening.
The Demo Project enrolled 557 MSM and transgender women at risk for HIV at STI clinics and community health centres in San Francisco, Miami and Washington, DC. All received once-daily Truvada PrEP on an open-label basis for a year. Nearly half of participants were white and the median age was 35 years.
Participants were tested for syphilis and for urethral, rectal and pharyngeal (throat) chlamydia and gonorrhoea at initial screening and every three months after starting PrEP; those who tested positive were promptly treated. They were considered asymptomatic if they reported having no STI symptoms on a structured symptom review and did not have any signs on a physical exam.
Just over a quarter of participants tested positive for an STI at the initial screening visit, falling to under 20% at the six-month follow-up visit and returning to 25% at 12 months – the opposite of the pattern seen in the SPARK study. At all visits rectal chlamydia or gonorrhoea were most common, followed by throat chlamydia or gonorrhoea, urethral chlamydia or gonorrhoea, and early syphilis.
The researchers found that 40% of chlamydia, 34% of gonorrhoea and 20% of syphilis cases detected during quarterly screening would have been missed if screening had been done only semi-annually or based on symptoms. Overall, treatment would have been delayed for 35% of participants if screening had been done every six months.
Further, 159 chlamydia infections (76%) and 150 gonorrhoea infections (83%) would have been missed if only genital screening had been done, and not also screening of the rectum and throat.
Most participants (89%) with asymptomatic STIs reported condomless sex between visits, indicating that the potential transmission period would have been extended by up to three months with less frequent testing. Screening every three rather than every six months prevented an average of eight, and a median of three, sex partners from being exposed for each STI diagnosis.
"A significant proportion of gonorrhoea, chlamydia and syphilis infections would have been missed if screening had been conducted every six months or if extra-genital screening had not been performed," the researchers concluded.
Golub S et al. STI data from community-based PrEP implementation suggest changes to CDC Guidelines. Conference on Retroviruses and Opportunistic Infections, Boston, abstract 869, 2016.
Cohen S et al. Quarterly STI screening optimizes STI detection among PrEP users in the Demo Project. Conference on Retroviruses and Opportunistic Infections, Boston, abstract 870, 2016.