Slowing Resurgent Syphilis in People With HIV

A German study of 1052 MSM newly infected with HIV from 1996 through 2007 logged an overall syphilis prevalence of 26%.²⁵ Syphilis prevalence in these members of the German HIV-1 Seroconverter Cohort surged from 10% in 1996-1999 to 35% in 2005. Syphilis prevalence at HIV diagnosis rose from 2.3% in 2000 to 16.9% in 2003 (P < 0.001), then fell back to 4.3% in 2007.

Although MSM account for most newly recorded syphilis cases in developed countries, syphilis remains a palpable threat to women, especially those with HIV. A 1999-2005 European Collaborative Study of HIV-positive pregnant women showed that syphilis prevalence was lower in European women than in MSM, but syphilis was the most common bacterial STI among women, affecting 2% of these 530 Western European women and 520 Ukrainian women.²⁶

In the United States syphilis incidence dwindled consistently among US women after 1990, but a rebound began in 2004 as syphilis incidence rose from 0.8 per 100,000 women that year to 1.0 per 100,000 in 2006.¹⁴ Among US women the rate of primary and secondary syphilis climbed 11.1% from 2005 to 2006, nearly matching the 11.8% jump among US men in that period.

A 2002 CDC study matching reported cases of syphilis and HIV found that 1718 of 6862 cases of primary or secondary syphilis (25%) affected HIV-positive people.²⁷ Syphilis incidence -- the new diagnosis rate -- was 77 times higher in HIV-positive people than in the general population. In 2002 new cases of primary or secondary syphilis occurred in 25 of 100,000 HIV-positive women, 60 of 100,000 HIV-positive men who had sex only with women, and 336 of 100,000 HIV-positive MSM.

In California, the epicenter of the US syphilis epidemic, researchers at Kaiser Permanente Northern California counted 622 new diagnoses of syphilis in 9989 HIV-positive people (6.6%) from 1995 through 2005, compared with 3584 new syphilis cases in 4,442,780 HIV-negative people (0.08%).²⁸ Syphilis incidence stood at 62.3 per 1000 person-years in the HIV group versus 0.8 per 1000 person-years in the non-HIV group. Statistical analysis adjusted for age, gender, and HIV status determined that HIV-positive people had an 86 times higher syphilis risk (P < 0.01). In the same analysis, women had a 10% lower syphilis risk than men. In both HIV-positive and HIV-negative people, syphilis incidence waned from 1995 through 2000 but then rose sharply in the HIV group (from 3.1 per 1000 in 2000 to 17.4 per 1000 in 2005). Syphilis incidence did not rise in the HIV-negative group after 2000.

In an Amsterdam Cohort Study of 863 gay men averaging 25 years in age, HIV and STI incidence paralleled each other through 1995.²⁹ At that point -- the threshold of the combination antiretroviral era -- syphilis incidence rose significantly (from 0 to 1.4 cases per 100 person-years), while HIV incidence stayed flat (1.1 to 1.3 cases per 100 person-years).

Studies of MSM in New York City³⁰ and San Francisco²¹ found that HIV infection independently raised the risk of syphilis -- more than 7 times in New York and almost 4 times in San Francisco (Table 2). All five recent studies on syphilis risk factors in MSM identified some type of risky sex as an independent predictor of syphilis. In New York,30 Brighton,³¹ and Sydney,³² unprotected anal intercourse made syphilis more likely -- and in Sydney that finding held true in HIV-positive and negative men.

The Brighton study found that having 2 to 4 oral sex partners doubled the syphilis risk compared with control MSM who did not have syphilis,³¹ and the Amsterdam survey determined that oral-anal sex -- rimming -- hiked the syphilis risk 5 times.³³ A 2000-2002 CDC study in Chicago found that 20% of MSM with primary or secondary syphilis reported oral sex as the only kind of sex they had during the study period.34

Having 10 or more casual sex partners doubled the risk of syphilis in Brighton.³¹ Finding partners on the Internet made syphilis twice as likely in San Francisco, as did reporting a strong gay community affiliation.²¹ Using methamphetamine with or without sildenafil upped the syphilis odds in San Francisco.²¹

The New York City researchers tied antiretroviral therapy to syphilis risk, perhaps because good responses to combination therapy led New York MSM to take more risks during sex.³⁰ Among HIV-positive men in that study, 69% with syphilis versus 44% without syphilis reported taking antiretrovirals (P = 0.05), and 58% with syphilis versus 24% without syphilis said they had an undetectable viral load (P = 0.02).

All these studies involve men in big cities with lengthy HIV epidemics, so syphilis risk factors may differ in other MSM populations. And none of these studies identified an intuitive risk factor for syphilis: people who get syphilis once run a high risk of getting it again. Christina Marra, who studies syphilis and HIV at the University of Washington, Seattle, told RITA! that 123 of 901 people in her syphilis cohort (14%) have come back with recurrent infection from 1 to 5 times. Besides persistence of the same risk behaviors, she believes that evolution of the spirochete puts people at risk of reinfection.

The syphilis reinfection rate is even higher in a Baltimore cohort at Johns Hopkins University. In an interview in this issue of RITA!, Khalil Ghanem estimates the overall reinfection rate at 30% in the 3 years of initial syphilis therapy.

HIV Incidence in People With Syphilis

Intuition -- if not hard numbers -- suggests that HIV incidence should jump in tandem with syphilis incidence: Syphilitic chancres offer wide portals for HIV to enter the circulation; CD4-cell homing to inflamed lesions provides a brimming population of HIV-susceptible cells; and syphilis-induced immune activation would ratchet up HIV replication.¹⁵ Also, syphilis boosts HIV load in already infected people,¹⁵ and people with higher viral loads transmit HIV more readily than those with lower loads.

The CDC figures that people with syphilis run a 2 to 5 times greater risk of HIV infection if exposed to HIV when they have syphilis sores.⁷ But the CDC stresses that -- at least through 2005 -- data collected in the United States make it impossible to say whether HIV incidence climbs among MSM during syphilis outbreaks in this country.¹⁵ Findings from San Francisco, Los Angeles, and Seattle-Kings County, Washington, uncovered no hint that HIV incidence jumped among MSM getting tested for HIV during syphilis outbreaks.¹⁵ And because most US data on HIV and syphilis incidence come from big cities with large gay populations and established HIV epidemics, those findings cannot explain what's happening across the country.

Data from other countries are mixed. As already noted, syphilis incidence rose significantly after 1995 among MSM in the Amsterdam Cohort, while HIV incidence stalled.²⁹ Germany, on the other hand, saw a surge in coincident HIV and syphilis from 2000 (2.3% of new HIV diagnoses) to 2003 (16.9%), then a decline (to 4.3%) in 2007.²⁵

CDC researchers tried to pin down HIV incidence in men with primary or secondary syphilis in a 2004-2005 study of 357 men in Atlanta, San Francisco, and Los Angeles.³⁵ Most of these men, 85%, were MSM, and 160 (45%) tested positive for HIV. Of those 160, 8 had recent infection, and 7 of those 8 were MSM. The CDC reckoned that HIV incidence among men with primary or secondary syphilis in these three cities stood at 9.5% per year -- and at 10.5% per year in MSM.

Two other US studies suggest frequent HIV transmission just before, just after, or during a period of syphilis acquisition.^36,37 Those findings, the CDC says, "are consistent with other studies indicating that a substantial proportion of recently and acutely HIV-infected persons have genital ulcer disease or other STDs and can be identified at the STD clinics."¹⁵

But these findings^35-37 do not mean HIV incidence billows whenever syphilis incidence climbs. The CDC concluded its 2005 review of HIV incidence in the midst of a syphilis epidemic by cautioning that, "with the limited existing data, we cannot say whether HIV incidence has been increasing among MSM during syphilis outbreaks in the United States."¹⁵ But, the CDC analysts add, "we do know that, to date, syphilis outbreaks have been concentrated among urban MSM, the majority of whom are HIV infected."¹⁵

What happened after 2005? As already noted,²² a 27-state CDC study confirmed an unabated surge in primary and secondary syphilis among MSM through 2008. Compared with white MSM, black MSM had an 8 times higher absolute increase in the rate of primary or secondary syphilis, and Hispanic MSM had a 2.4 times higher rate increase. Men from 20 to 29 years old endured the biggest syphilis hikes in this analysis. The CDC investigators believe their findings "suggest a marked shift in the epidemiology of primary and secondary syphilis in the United States in recent years, specifically with regard to MSM."²² In the first years of this century, studies disclosed outbreaks of primary and secondary syphilis among MSM in their 30s, but the 2005-to-2008 CDC study found that men under 30 -- and black and Hispanic men -- bore the brunt of new syphilis infections.

These syphilis findings track with the CDC's most recent HIV incidence report, covering the years 2006 through 2009.³⁸ In the United States overall HIV incidence stayed flat in those years, but incidence soared 34% among young MSM and 48% among young black MSM. Among all 13- to 29-year-olds, only MSM had a significant jump in HIV incidence, and among 13- to 29-year-old MSM, HIV incidence rose most among blacks. Together, these studies^22,38 suggest that syphilis and HIV incidence are climbing in tandem -- and climbing fastest in young, black MSM.