STDs pose major health threat to MSM

Sexually transmitted diseases have become a significant public health challenge in the United States, and in particular, the burden of disease in men who have sex with men shows no signs of abating.

Cases of primary and secondary (P&S) syphilis are rising nationally, especially among MSM, according to the CDC’s 2013 National Data for Chlamydia, Gonorrhea, and Syphilis. Cases of chlamydia and gonorrhea declined slightly in the general population, but appear to be increasing for MSM.

Edward W. Hook III, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, stressed the importance for clinicians to assess and treat patients as individuals instead of painting them with a broad brush. Still, he acknowledged that MSM are at greater risk than the general population.

“I don’t want to suggest to anybody that every man who has sex with other men is at high risk for STDs. However, when you look at statistics, at the present time, as a subgroup, rates of a number of sexually transmitted infections are higher in men who have sex with men than they are in subgroups of people who have opposite sex partners,” he said.

Photo courtesy of Workowski KA

Increased access to online dating services, high-risk behavior and significant challenges to screening and treatment are just some of the reasons behind the increased susceptibility to STDs among MSM, according to experts.

Infectious Disease News spoke with physicians and researchers about the growing problem of STDs in MSM, its root causes, and what infectious disease specialists are doing to improve health outcomes.

STDs by the numbers

P&S syphilis data is based on national surveillance, according to Kimberly A. Workowski, MD, professor at Emory University, and co-author of the CDC’s 2015 Sexually Transmitted Diseases Treatment Guidelines. Data on chlamydia and gonorrhea are based on the CDC’s STD Surveillance Network (SSuN), which has been collecting information from 42 STD clinics in 12 jurisdictions across the U.S. since 2005.

“The CDC really doesn’t collect any sexual behavior data except for data on primary and secondary syphilis, and so we glean a lot of this information on other STDs from studies that have been looking at cohorts and sentinel surveillance,” Workowski told Infectious Disease News.

While chlamydia and gonorrhea saw overall decreases of 1.5% and 0.6%, respectively, per 100,000 people from 2012 to 2013, P&S syphilis rates increased 10% during the same period, according to the CDC. Data indicate that the increase is almost entirely attributable to men, primarily MSM. A CDC report on syphilis and MSM suggested that 75% of all P&S syphilis cases reported in 2013 were from this population. A P&S syphilis rate of 5.5% per 100,000 Americans was the highest since 1996, according to Workowski.

Annual STD reports from the CDC show that in 2000, syphilis rates in the U.S. were 2.1 per 100,000 — the lowest level they had been since 1941. From 2000 to 2013, however, the rate of P&S syphilis among men increased fourfold from 2.7 per 100,000 to 10.3 per 100,000. In areas where information was available, 52% of MSM with P&S syphilis were coinfected with HIV.

Surveillance data from the SSuN STD clinics show that similar numbers of MSM were tested for chlamydia (20,710) and gonorrhea (20,955) in 2013, with a median percentage of infections of 15.2% and 16.9%, respectively. The same report for 2012 shows that approximately 22,000 MSM were tested for each STD, with 12% testing positive for chlamydia and 16.4% for gonorrhea.

Based on 2008 figures, the CDC estimates there are nearly 20 million new STDs in the U.S., with those aged 15 to 24 years accounting for 50% of infections. HPV, which most sexually active people will acquire at least once in their lives, accounts for more than 14 million of these new infections.

According to these same figures, approximately 79 million Americans are now infected with HPV. The virus causes approximately 360,000 cases of genital warts in the U.S. annually, and 11,000 cases of cervical cancer.

Americans have an estimated 422,000 sexually transmitted hepatitis B infections, with 19,000 new infections yearly, and the STD is more common in MSM due to its transmissibility through sexual activity and body fluids.

Gwenda Hughes, PhD, FFPH, consultant scientist in epidemiology and head of the sexually transmitted infection section of Public Health England’s HIV and STI department, said the problem of STDs in MSM also is growing in the United Kingdom.

“Large increases in STD diagnoses were seen in MSM, including a 46% increase in syphilis and a 32% increase in gonorrhea,” she told Infectious Disease News. “Increased testing may have accounted for much of the rises in chlamydia and gonorrhea, especially between 2010 and 2012 following changes in testing guidelines that led to more extragenital testing. However, recent rises in MSM are most likely a consequence of more condomless sex, likely associated with HIV seroadaptive behaviors facilitated by geospatial sexual and social networking apps.”

Natalie N. Vanek, MD, an infectious disease physician at Legacy Community Health Services, Montrose Clinic, Houston, noted a significant increase in STDs among MSM in her area, as well.

“They’re coming in droves with syphilis,” she told Infectious Disease News. “We have a tremendous outbreak of syphilis here in Houston, and the other STDs as well. I know that it is being fueled by sex dating sites, and it’s also being fueled by a drug epidemic.”

A combination of factors

So why are MSM more vulnerable to STDs?

“I think it’s complicated. It’s been documented in terms of the literature — that increases in syphilis among MSM have included things like methamphetamine use, multiple anonymous partners, seeking partners through the Internet, having greater than 10 recent sexual partners,” Workowski said, adding that the advent and use of erectile dysfunction drugs such as Viagra (sildenafil citrate, Pfizer) and Cialis (tadalafil, Eli Lilly) have encouraged more continuous sexual performance and group sex among MSM. “The other thing is when you have extragenital activity and most of the infections are asymptomatic in terms of the rectum and the pharynx, you can understand how these things can be transferred back and forth between people.”

In a 2011 research paper published in Clinical Infectious Diseases, Kenneth H. Mayer, MD, medical research director at The Fenway Institute in Boston and Harvard Medical School professor, suggested the reasons for the disproportionate burden of disease in MSM are complex and include a range of biological, sociocultural and behavioral factors.

“It’s not as if we have a fixed number of how many men who have sex with men there are, because it’s behavior. There’s attraction, orientation, behavior, identity — and these things don’t always map together,” Mayer said in an interview. “We certainly know there are several million men who have sex with men, and some of those individuals are in stable, monogamous relationships, but some of them are not.”

MSM also are more prone to engage in insertive or receptive anal intercourse, increasing the likelihood of infection.

“So certainly infections like rectal chlamydia or gonorrhea would be particularly prevalent in this population,” Mayer said. “Epidemiologically, almost by definition, men who have sex with men are a minority population and are more likely to choose partners who are other men who have sex with men. Once an infection gets into a smaller community, the likelihood of the infection ping-ponging within that community becomes higher.”

However, Mayer said traditional relationship conventions such as monogamy and marriage are not necessarily a consistent part of the MSM culture, which also may play a role.

“Although it’s not generalizable to all men who have sex with men, some men who have sex with men — historically not having social sanctions of marriage or some of the same social norms around partnerships — may have multiple sexual partners within a fairly short period of time,” Mayer said. “Those individuals are not only biologically more susceptible to some of the infections, but the behavior may put them at high risk for infection.”

Importantly, MSM vulnerability also may stem from a lack of access to information and treatment, according to Hook.

“Issues related to STDs are a fundamental concern for men who have sex with men,” he said. “There’s some debate as to whether those are issues related to current behaviors or legacy issues regarding the fact that perhaps, in at least some communities, men who have sex with men have been marginalized and haven’t had the same sort of health care opportunities as other members of our society.”

‘Screen, treat, treat, screen’

According to infectious disease specialists, health care providers must be willing to discuss sexual history with their patients and screen MSM at every opportunity. This is especially true, Workowski said, because many MSM may not know they have an STD.

“I think it’s important for providers, especially infectious disease providers who are seeing men who have sex with men either at risk or who already have HIV infection, to take a detailed sexual history at each visit,” she said. “If there was exposure at the correct anatomical sites, they should test for chlamydia and gonorrhea and also do regular testing for syphilis, because the extragenital sites are mostly asymptomatic. You can also pick up a lot of early latent syphilis by doing regular screening.”

Asking questions can be especially helpful in identifying asymptomatic STDs caused by anal and oral sex at the rectum and pharynx, respectively, Workowski added.

“A lot of times patients will come into emergency rooms complaining of rectal bleeding and rectal pain, and if they’re diagnosed with rectal bleeding, the physician will take a scope and look inside, and sometimes they may be misdiagnosed with inflammatory bowel disease, which can have the same symptoms,” she said. “If somebody comes in with rectal bleeding, the physician should ask if they’ve been having receptive rectal intercourse ... the patient can have syphilis, they can have gonorrhea, they can have herpes or proctitis. The important thing is they need to be aware that this could be potentially sexually transmissible.”

The CDC recommends annual screenings for sexually active MSM for syphilis, chlamydia, gonorrhea and HIV, and screenings for those with multiple or anonymous sex partners at least every 6 months. Those who use illicit drugs or whose partners use drugs also may benefit from additional screenings.

Hook added: “An important question for any health care provider who is taking care of any American who is sexually active is, ‘Who are your sex partners, and how many are there?’ ”

Mayer said some PCPs may screen patients for STDs for whom they “have a higher index of suspicion,” but they need to be more inclusive.

“There’s no magic bullet — some things work for some people and not for others. The most important intervention for bacterial sexually transmitted infections is routine screening, because getting people to change behavior can be very challenging,” he said. “If the interval between screenings is short, the likelihood that somebody has acquired the infection and passed it on to a new partner is decreased substantially. Because gonorrhea, chlamydia and syphilis are highly treatable, we encourage frequent screening.”

Mayer said The Fenway Institute, for example, recommends quarterly STD screenings for sexually active people with multiple partners.

Vanek recommended that physicians check the CDC’s STD treatment guidelines at least once a year, especially in light of the growing problem of drug-resistant gonorrhea, and work to develop peer-based interventions for MSM. Perhaps most importantly, she urged physicians to be aggressive when it comes to testing.

“I just want to hammer this home — test everywhere,” she said. “As ID physicians, we need to get everybody to start checking those extra urethral sites and test, because if we don’t do that, we’re missing it.”

Discussing the role of the physician, Jeffrey D. Klausner, MD, MPH, professor of medicine and public health at the David Geffen School of Medicine and Fielding School of Public Health at the University of California, Los Angeles, offered the mantra: “Screen, treat, treat, screen.”

“We’re unlikely to be successful at changing behavior,” he said, “but we can find these infections. They’re easily treatable, and we can have a public benefit if we keep screening and treating.”

While physicians know what medications work and may be informed about any crossover coverage these drugs can offer, patients can harbor misguided and potentially harmful assumptions if not educated properly.

Vanek said it is critical for physicians to remind patients that receiving pre-exposure prophylaxis (PrEP) does not make them immune to other STDs.

“To me, this is one part of the education piece that we really need to focus on for patients, that even though you’re on PrEP, you still need to ask your partners, ‘Do you have any other STD risk at this time?’ ”

In addition to actively screening for STDs like gonorrhea, chlamydia and syphilis, Vanek urged physicians to routinely recommend HPV vaccination to their patients.

“This needs to be routine for everyone, so we can cut down on our incidences, especially for MSM, for oral and anal cancer,” Vanek said. “The statistics for that are so devastating, and that’s a preventable cancer. Anal cancer in our young MSM is just atrocious, and it’s so preventable. We need to STD test at all body sites. That is what I’ve learned here at my own clinic: We are totally missing these STDs if we don’t do this.”

Everyone’s problem

MSM may represent a relatively small population, but the high burden of STDs can have serious consequences.

Syphilis, along with other STDs such as gonorrhea, chlamydia and herpes simplex virus type 2, is known to facilitate the risk for acquiring HIV. The diseases are acquired through the same high-risk behaviors, and genital ulcers caused by syphilis also offer a portal of entry for HIV infection when they come into contact with oral and rectal mucosa during sexual activity. The presence of syphilis carries a two- to fivefold increased risk for HIV, according to the CDC.

In a substudy of the Pre-exposure Prophylaxis Initiative (iPrEx) trial, which evaluated the safety and efficacy of Truvada (tenofovir/emtricitabine, Gilead Sciences) as PrEP for MSM and transgender women, researchers found that 333 of 2,499 study participants had a positive confirmatory test for syphilis via PCR. The overall incidence of syphilis during the trial was 7.3 cases per 100 person-years. However, according to the researchers, syphilis did not reduce the protective effect of PrEP.

Moreover, there are numerous adverse sequelae associated with STDs that can affect not just MSM but those in the general population — including infertility and cervical cancer among women and congenital infections — further emphasizing the need for prompt screening and treatment.

“STDs like syphilis can lead to blindness and deafness and strokes,” Klausner said. “In addition, the STDs, particularly rectal STDs like gonorrhea and chlamydia, can increase the risk for acquiring HIV, and there are some early studies suggesting that bacterial STDs might be a co-factor increasing the risk for anal cancer from HPV infection.”

Klausner said it is difficult to attribute increases in STDs in the general population to the rise in cases in MSM, but both “reflect the current loss and defunding of public health programs” that are essential to reducing the prevalence of infections across numerous patient populations.

The impact of social media on STDs

Websites and smartphone apps like Craigslist, Tinder and Grindr provide new opportunities to meet sex partners. They also create challenges for public health departments trying to prevent the spread of STDs.

“With the advent of social media sites, there’s been an increased opportunity for people to meet partners in an anonymous way. Unfortunately, we don’t have really good research to support this link between social media apps or dating online apps with STD rates,” Workowski said.

While information on social media and STDs is lacking, new light recently has been shed on the use of social media and its impact on HIV infection. A recent study in MIS Quarterly suggests the introduction of Craigslist was related to an average 15.9% increase in cases of reported HIV. This equates to a yearly estimate of 94 new cases of HIV infection per state, 6,130 to 6,455 new cases nationally, and $62 million to $65.3 million in treatment costs.

“There are specific social networking sites where people develop profiles, and that’s where people go to meet new sexual partners,” Mayer said. “The Internet has become a much more popular way for men to meet partners than in bars. It’s not like a health care worker can station themselves at the bar and hand out health information. It requires the development of a different set of skills on the part of health departments, but many health departments now have ways of notifying people online that they’ve been exposed and educating people to come in, where they can get tested and receive services.”

Mayer said the Massachusetts Department of Health attempts to trace contacts of those with STDs. When the contact is made online, however, the process can become much more difficult.

“The challenge is, if someone meets a partner online ... some individuals will be embarrassed because they have the STD and not be comfortable disclosing the information,” Mayer said. “There may be situations where they think the person will be angry with them or hurt them, so they are reticent. Then there are some individuals who really don’t know the partner other than a screen name.”

Hook said online dating sites “have helped societywide to transform sex from a reproductive health practice to a pursuit of pleasure practice.” Casual sexual encounters are therefore easier and more frequent, increasing the risk for STDs, he said.

Some online dating sites offer serosorting and other services to help users avoid partners with STDs. Hughes said serosorting is a mixed blessing for MSM. Men are better able to avoid sex partners with transmissible diseases, but this may make them feel as though they do not need to use condoms, which can lead to more STD transmission, she said.

Klausner noted that California provides recommendations to online dating sites, including the promotion of good health and the creation of user profiles with HIV statuses and disclosures of STD testing and results. He serves as an unpaid medical adviser for Healthvana, a patient-engagement platform that offers certified STD testing information, which patients can post on dating sites.

“If there’s more regular outreach and interventions using those apps, I think they could have a greater impact on the epidemic,” he said.

The added challenge of antibiotic resistance

The issue of increasingly drug-resistant gonorrhea is a major obstacle for treatment, especially among MSM, according to Hughes.

“What we’ve seen, particularly in the last 10 years or so, is that when a new strain emerges, which is either resistant or showing decreased susceptibility, it tends to emerge first among men who have sex with men,” she said. “That’s certainly what we saw in [in the last 6 or 7 years] when we were routinely using [Suprax (cefixime, Lupin)]. There’s just a lot more transmission among men who have sex with men so they are more often exposed to the infection and to the treatment. Therefore, a resistant or less susceptible strain is more likely to emerge.”

Hughes said this reinforces the need to reduce transmission of gonorrhea among MSM and the rest of the population, “so we can prolong the use of the drugs we currently have to treat it.”

Educating MSM about drug resistance and encouraging condom use is critical, she added.

Hughes said the current cephalosporin treatment used in England has proven highly effective, but like other physicians, she has seen it become increasingly less effective against gonorrhea.

Until recently, dual therapy of cephalosporin ceftriaxone and azithromycin or doxycycline was the only CDC-recommended regimen for treating uncomplicated gonorrhea.

However, the new CDC treatment guidelines highlight alternative treatment options. Specifically, the combination treatment of oral gemifloxacin 320 mg plus oral azithromycin 2 g, or dual treatment with single doses of intramuscular gentamicin 240 mg plus oral azithromycin 2 g, have been shown to be effective against uncomplicated urogenital gonorrhea, Workowski said, with cure rates reaching 99.5% and 100%, respectively. The updated guidelines suggest these regimens can be used in place of cephalosporin.

“[Gonorrhea] is very savvy at developing resistance to antibiotics,” Workowski said. “It’s a really important addition to this version of the guidelines, especially in people who have allergies to the only known remaining antimicrobial, which is cephalosporin.”

The CDC’s most recent drug resistance threat report estimated that there were 800,000 cases of gonorrhea in the U.S. in 2011, 30% of which were resistant to any antibiotic.

Should cephalosporin-resistant Neisseria gonorrhoeae become widespread, the CDC says there will be up to 75,000 additional cases of pelvic inflammatory disease — a major cause of infertility — along with 15,000 cases of epididymitis and more than 200 cases of new HIV infections, all within a 10-year period. Direct medical costs could total $235 million, according to the report.

Klausner said the issue of drug-resistant STDs, particularly gonorrhea, is a growing problem worldwide. Since MSM tend to develop drug resistance more rapidly than the general population, the issue looms very large for this population.

“We’ve seen some steady increases in resistance in the United States to third-generation cephalosporins, which is our last line of antibiotic treatment,” he said. “We’ve seen sporadic resistance to some of our other medications, and right now we’re not treating gonorrhea the smartest way we can.”

Klausner said that using the dual-therapy treatment of ceftriaxone and azithromycin or doxycycline for all gonorrhea is a flawed solution.

“We need to be able to treat it smarter like we do many other infectious diseases, based on its susceptibility profile,” he said. “Gonorrhea is diagnosed with a PCR. There hasn’t been a strong enough push to build into those PCRs tests for susceptibility to antibiotics.”

He added that PCR for staphylococcal infections and tuberculosis are examples of tests that measure this susceptibility, but they have not been replicated yet for gonorrhea due to expenses associated with its production. He said the federal government may have to step up in place of diagnostic companies to develop the new gonorrhea tests.

Hook recently took part in a phase 2 clinical trial of solithromycin (Cempra), primarily indicated for moderate to moderately severe community-acquired bacterial pneumonia and urethritis. However, the company also is looking at the use of oral solithromycin in patients with uncomplicated gonococcal infections. Recent data demonstrated that a single dose of oral solithromycin cleared infection in all 46 evaluable patients. A phase 3 clinical trial is currently underway, but Hook said the drug is at least 2 years away from FDA approval.

Improving outcomes in MSM

Klausner said he is optimistic that outcomes will improve for MSM with regard to STDs. One reason is the arrival of PrEP for HIV, which brings more high-risk patients to STD clinics.

“As part of PrEP service care and treatment, [patients] need to see a doctor or some kind of provider every 3 months [at UCLA Health],” he said, “So every 3 months ... they are getting syphilis testing, chlamydia testing, gonorrhea testing, their vaccine status is up to date, and if they are found with an infection, they get treated quickly and their partners get treated quickly. That could have a profound effect on the rate of new infections.”

Aside from the timely screening and treatment of STDs, Hook said improvements in the health of MSM also are tied to the acceptance of homosexuality.

“I am hopeful that the societal change underway in the United States that was most recently advanced through the Supreme Court’s decision on same-sex marriage will continue, and that we can improve health care for everybody,” he said. “I think the issues that surround sexuality in general, and for men who have sex with men specifically, fuel a tendency toward stigma and stigmatization, and that’s something as health care providers we need to actively resist.”

STDs are a significant health problem for MSM as well as for the general population. More infections mean more opportunity for transmission and an increased likelihood of drug resistance.

“Sexually transmitted infections are not someone else’s problem. It’s an active and important concern for all of our patients,” Hook said.

According to Hughes, a successful defense against STDs — especially among MSM who exhibit high-risk sexual behaviors — begins and ends with a single responsible act.

“Unless we start to get a ‘safer sex’ message across about the importance of using condoms, I think then we will see a lot more transmission of these infections and even higher rates than we’re seeing now, unfortunately,” she said. – by David Jwanier

• References:
• CDC. Antibiotic Resistance Threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf#page=55. Accessed July 20, 2015.
• CDC. Incidence, prevalence, and cost of sexually transmitted infections in the United States. 2013. http://stacks.cdc.gov/view/cdc/13174/. Accessed July 20, 2015.
• CDC. Reported STDs in the United States: 2013 national data for chlamydia, gonorrhea, and syphilis. 2014. http://stacks.cdc.gov/view/cdc/26427. Accessed July 20, 2015.
• CDC. STDs in men who have sex with men. 2013. http://www.cdc.gov/std/stats13/msm.htm. Accessed July 20, 2015.
• CDC. Syphilis and HIV: A Dangerous Duo Affecting Gay and Bisexual Men. 2012. https://blog.aids.gov/2012/12/syphilis-and-hiv-a-dangerous-duo-affecting-gay-and-bisexual-men.html. Accessed July 23, 2015.
• CDC. Syphilis & MSM (Men Who Have Sex With Men) - CDC Fact Sheet. 2015. www.cdc.gov/std/Syphilis/STDFact-MSM-Syphilis.htm. Accessed July 20, 2015.
• Chan J, et al. MIS Quarterly. 2014;38:955-976.
• Heffelfinger JD, et al. MMWR. 2002;51:971-973.
• Mayer KH. Clin Infect Dis. 2011;doi:10.1093/cid/cir696.
• Patton ME, et al. MMWR. 2014;63:402-406.
• Solomon MM, et al. Clin Infect Dis. 2014;doi:10.1093/cid/ciu450.
• Workowski KA, et al. MMWR. 2015;64:1-137.

• For more information:
• Edward W. Hook III, MD, can be reached at ehook@uab.edu.
• Gwenda Hughes, PhD, FFPH, can be reached at gwenda.hughes@phe.gov.uk.
• Jeffrey D. Klausner, MD, MPH, can be reached at JDKlausner@mednet.ucla.edu.
• Kenneth H. Mayer, MD, can be reached at Kmayer@fenwayhealth.org.
• Natalie N. Vanek, MD, can be reached at nvanek@legacycommunityhealth.org.
• Kimberly A. Workowski, MD, can be reached at kworkow@emory.edu.

Disclosures: Hook, Hughes, Vanek and Workowski report no relevant financial disclosures. Klausner reports that he is an unpaid medical adviser to Healthvana. He has received donated gonorrhea and chlamydia test kits from Hologic and Cepheid. Mayer reports that The Fenway Institute has received unrestricted educational and research grants from Bristol-Myers Squibb, Gilead Sciences and Merck.

Should MSM who are diagnosed with primary or secondary syphilis receive HIV pre-exposure prophylaxis?

We should recommend that HIV-uninfected MSM with early syphilis initiate PrEP.

In 2013, an estimated 67% of all new HIV diagnoses in the United States occurred in men who have sex with men, a group that constitutes approximately 2% of the population. Although some parts of the country are experiencing declines in HIV incidence among MSM, many are not as the epidemic grows more concentrated, more focused on the southern U.S. and young black MSM. We need to do more to prevent HIV infection.

Pre-exposure prophylaxis (PrEP) is part of the solution. However, defining the target population for PrEP is not simple. Cost-effectiveness analyses have consistently found that PrEP is not cost-effective if given to the broad population of MSM regardless of risk. CDC guidelines recommend that medical providers consider prescribing PrEP to MSM patients who are outside of long-term, HIV-seroconcordant, mutually monogamous relationships if the patient has had any condomless anal sex or a bacterial STD in the prior 6 months, or if they have an HIV-infected partner. These guidelines are an excellent start, but are very broad. Pharyngeal gonorrhea poses a different risk for future HIV acquisition than rectal gonorrhea. Sex with an HIV-infected partner suppressed on ART is not the same as sex with a partner who is off ART. Moreover, the incidence of HIV varies dramatically in different populations. Based on surveillance data, the incidence of new HIV diagnoses among MSM in Miami is approximately five times that observed in Seattle. An alarming report from Atlanta found that the annual incidence of HIV among young black MSM was almost 11%. How we target PrEP needs to vary depending on the population served. In some populations, medical providers should probably recommend PrEP to almost all MSM regardless of reported risk. In other populations, a risk factor-guided approach makes sense. We are going to need local guidelines to help medical providers define the populations that need PrEP. Those guidelines will also need to be more assertive than current CDC guidelines. “Consider” is not good enough. There are times when medical providers need to make a clear recommendation.  

So who needs a clear recommendation? The right answer will vary depending on where you live and the patient population you serve. But there are some populations that are always at high risk, where a strong national recommendation is straightforward. MSM with syphilis or rectal gonorrhea are such a group. Studies have consistently shown that these two infections are associated with a high risk for HIV acquisition. I also believe that providers should routinely recommend PrEP to MSM who use methamphetamine, which is often the single strongest predictor of future HIV acquisition. Of course, as with any medical treatment, patients will ultimately decide what they want to do. But we should be clear. We recommend that HIV-uninfected MSM with early syphilis initiate PrEP. This is a minimum standard and should not be controversial.

• References:
• Juusola JL, et al. Ann Intern Med. 2012;156:541-550.
• Menza TW, et al. Sex Transm Dis. 2009;doi:10.1097/OLQ.0b013e3181a9cc41.
• Pathela P, et al. Clin Infect Dis. 2015;doi:10.1093/cid/civ289.
• Pathela P, et al. Clin Infect Dis. 2013;doi:10.1093/cid/cit437.
• Schneider K, et al. Clin Infect Dis. 2014;doi:10.1093/cid/cit946.
• Sullivan PS, et al. Ann Epidemiol. 2015;doi:10.1016/j.annepidem.2015.03.006.

Matthew R. Golden, MD, MPH, is the director of Public Health – Seattle and King County HIV/STD Program, Washington. He is also a professor of medicine at University of Washington Harborview Medical Center. Disclosure: Golden reports receiving research support from Cempra and Melinta Therapeutics.

Yes, provided there are no contraindications and the patient can adhere to PrEP.

Syphilis rates are increasing in many parts of the world. HIV-infected persons, particularly MSM, are disproportionately affected. Two recent studies provide additional insights. The first study, nested within the Pre-exposure Prophylaxis Initiative — or iPrEx — study, reported a 2.6-fold increased risk for HIV seroconversion in MSM with an incident syphilis infection compared with MSM without. The use of PrEP in the iPrEx study significantly reduced the risk for HIV seroconversion and did not result in behavioral disinhibition (indeed, studies to date have not shown an increase in risk-taking behaviors among PrEP users). To prevent one incident HIV infection in iPrEx, approximately 30 MSM with syphilis would need to receive PrEP (the average number needed to treat [NNT] to prevent a single HIV infection was 62). Only MSM reporting condomless receptive anal intercourse and those using cocaine had lower NNTs. Similarly, a study conducted by the New York City Department of Health found that the annual HIV incidence for MSM diagnosed with early syphilis was nearly 5.5%. To place that estimate into context, if the annual HIV incidence within a population is 2.4%, 40% of those who are HIV-uninfected at age 18 years will have acquired HIV by age 40 years. These studies and others clearly demonstrate that early syphilis is an important predictor of HIV acquisition, likely as a result of both biological and behavioral factors.

We also know, based on the results of several randomized controlled trials, that PrEP is highly effective at preventing HIV acquisition in MSM if used consistently. Consequently, the consistent use of PrEP among MSM who are diagnosed with early syphilis could significantly decrease their risk for acquiring HIV infection. Given these data, should all MSM diagnosed with primary or secondary syphilis receive PrEP? The answer is yes, with caveats. The 2014 U.S. Public Health Service guidelines recommend PrEP use by HIV-uninfected MSM who have any STD diagnosed or reported in the preceding 6 months. Thus, using PrEP in MSM who are diagnosed with primary and secondary (P&S) syphilis is perfectly in line with these guidelines. It is important to note, however, that screening for HIV infection should be conducted at least every 3 months, and renal function should be assessed at baseline and monitored at least every 6 months while patients are taking PrEP. Thus, as long as there are no contraindications to taking PrEP and the patient is able and willing to adhere to PrEP and subsequent screening recommendations (a critical part of the decision to start prophylaxis), MSM diagnosed with P&S syphilis should receive PrEP.

• References:
• Buchbinder SP, et al. Lancet Infect Dis. 2014;doi:10.1016/S1473-3099(14)70025-8.
• Pathela P, et al. Clin Infect Dis. 2015;doi:10.1093/cid/civ289.
• Solomon MM, et al. Clin Infect Dis. 2014;doi:10.1093/cid/ciu450.
• Stall R, et al. AIDS Behav. 2009;doi:10.1007/s10461-008-9509-7.

Khalil G. Ghanem, MD, PhD, is an associate professor of medicine at Johns Hopkins University School of Medicine. He is also Deputy director of education for the department of medicine at Johns Hopkins Bayview Medical Center. Disclosure: Ghanem reports no relevant financial disclosures.

PrEP should be offered to MSM with syphilis and to all MSM at risk for HIV.

The rates of P&S syphilis increased by 11% in 2012, 10% in 2013 and preliminary data show a similar increase in 2014. Men account for over 90%, with MSM now accounting for over 75% of all syphilis cases in the U.S. Syphilis is a marker of high-risk sexual activity and identifies core transmission sexual networks. The risk of ongoing transmission of HIV is reflected in the more than 50% coinfection rate of HIV with P&S syphilis in MSM. Although syphilis can be successfully treated with penicillin, it synergistically interacts with HIV in facilitating transmission of both infections and is estimated to increase HIV transmission two- to fivefold.

MSM with syphilis infection often are engaging in the same high-risk behaviors that lead to HIV infection. The high rate of HIV and syphilis coinfection among MSM would suggest these transmission networks are one and the same. Although treating syphilis in HIV-uninfected individuals is believed to lower the immediate risk for HIV acquisition, it does not alter the risk associated with future sexual exposure in these high-transmission networks.

The opportunity for combination prevention interventions can significantly reduce the risk for HIV acquisition. PrEP has now been demonstrated to be an effective key HIV prevention strategy component. The results from two recent PrEP studies, PROUD and IPERGAY, showed an effectiveness rate for PrEP of 86% among MSM. PROUD, in particular, studied the use of daily tenofovir/emtricitabine among high-risk MSM and reflected real-world use of PrEP as taken and not the ability to offer protection in those only with 100% adherence.

The challenge is in how to identify high-risk groups for targeted intervention. New syphilis infection is a way of identifying both these individuals and HIV high-transmission networks. Offering PrEP to HIV-uninfected MSM with syphilis and to their HIV-negative partners will put a highly effective prevention at the leading edge of transmission. Although there is the potential for an increase in unprotected sex with the use of PrEP, studies have not demonstrated a higher rate of STD acquisition or an increase in sexual risk taking while on PrEP. The high rate of syphilis/HIV coinfection would suggest that risk is already present within many MSM sexual networks. We must not lose sight of the prioritization of preventing HIV acquisition over other STDs, like syphilis, which we can cure with a single dose of an antibiotic. PrEP combined with routine screening for STDs, the use of condoms and risk reduction counseling can dramatically lower the HIV transmission rates and should certainly be offered to MSM with syphilis and to all MSM at risk for HIV.

• References:
• CDC, 2013 Sexually Transmitted Diseases Surveillance. http://www.cdc.gov/std/stats13/syphilis.htm. Accessed July 23, 2015.
• McCormack S, et al. Abstract 22LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle, Washington.
• Taylor MM, et al. J Acquir Immune Defic Syndr. 2015;doi:10.1097/QAI.0000000000000730.

Peter A. Leone, MD, is a professor of medicine at the School of Medicine and an adjunct associate professor of epidemiology at the University of North Carolina, Gillings School of Global Public Health. Disclosure: Leone is a speaker for Abbott Diagnostics.

Overall risk for HIV infection is made up of individual choices.

The question posed to me, however, was whether a single episode of early syphilis should be a sole indication for PrEP. A syphilis infection is a biomarker for sexual behavior choices known to increase one’s risk for exposure to and infection with HIV and, especially when it comes to sex, past behavior tends to predict future behavior. However, in most communities, the prevalence of syphilis is much lower than that of gonorrhea and chlamydia. In addition, per exposure, syphilis is harder to get than gonorrhea and chlamydia. Following this logic one might conclude that someone attending an STD clinic and found to have early syphilis must have had a higher risk profile (eg, sexual encounters that were some combination of more numerous, condomless, and with sexual network members who themselves had high-risk profiles and a higher prevalence of STDs and HIV) than those MSM clinic attendees who do not have syphilis. A syphilis infection, by this analysis, would be considered a more heavily weighted sentinel event than gonorrhea or chlamydia and thereby should make a stronger case for PrEP.

Regardless of whether it is syphilis or gonorrhea or chlamydia, a carefully taken (ie, nonjudgmental) sexual history may help tease out whether some or all of the risk profile components summarized above might be present (including drug and alcohol use, which can short-circuit intended sexual behavior choices). This analysis can help educate about nuances of how an overall risk for HIV infection is actually made up of individual choices, so an individual can better understand how they might reduce that risk by changing some behaviors. In any event, the exercise can help to make an informed decision about whether PrEP is right for them.

A single syphilis infection should certainly prompt a very serious conversation with the patient, and I would recommend PrEP if the patient had any doubt about their ability to follow through with intended behavior changes that would decrease their risk for HIV infection.

• References:
• CDC. Preexposure prophylaxis for the Prevention of HIV Infection in the United States – 2014. A Clinical Practice Guideline. www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. Accessed July 23, 2015.

Robert K. Bolan, MD, is the medical director and director of clinical research at Los Angeles LGBT Center.  He is also an associate professor of clinical family medicine at the University of Southern California Keck School of Medicine. Disclosure: Bolan has received research support from the NIH, NIAID, the NIAID Division of AIDS, and the California HIV/AIDS Research Program. He also serves on the HIV Simply Speaking speakers bureau.