Successful prevention of syphilis infection with azithromycin in both

HIV-negative and HIV-positive individuals, San Francisco, 1999-2003.

J. D. Klausner,1,2 K. Steiner,1 R. Kohn1

1San Francisco Dept Public Health, San Francisco, CA 2University of California, San Francisco, San Francisco, CA.

Background: Syphilis trends in San Francisco

EARLY LATENTPRIMARY & SECONDARY

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Background: Current syphilis epidemic in San Francisco

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Cases

GAY/BI MALE + TG

MALE UNK

HETERO MALE

FEMALE

Background:Previous studies on azithromycin and syphilis

• Hook EW, Stephens J, Ennis DM, Ann Intern Med, 1999– randomized trial of 1 gram azithromycin vs. 2.4 mu

benzathine penicillin for incubating disease– no reactive FTA-ABS at 3 months in either group

• Hook EW et al., Sex Trans Dis, 2001– RCT of azithromycin vs. benzathine penicillin for

syphilis cases– 2 grams of azithromycin as effective as benzathine

penicillin for treating disease

Background:Syphilis treatment in San Francisco

• Contacts: new cases versus “epi treatment”– 2.4 mu benzathine penicillin G I.M. (“bicillin”) – 100 mg doxycycline P.O. BID for 14 days– 1 gram azithromycin P.O.

• Field-delivered therapy with Azithromycin began March, 1999

Objective

• Compare observed success in treating incubating syphilis using azithromycin to success with other treatments in order to justify continued use of azithromycin

Methods:San Francisco STD Registry

• STD clinic medical record data

• Reported morbidity and reactive STS

• Interview data and field activity

• Screening data

Methods: Sample

• Data from 1999 through 2003

• Non-reactive RPR or VDRL with any syphilis treatment (n=3812)

• Follow-up titer between 30 and 90 days after initial titer (n=151)

Methods: Measurements

• Outcome: any reactive titer defines treatment failure

• Biological false positives excluded from analysis

• HIV status measured from multiple sources, including self-reported status

Results:All patients

confidence limitsTreated Failures Percent lower upper

TreatmentArithromycin 1G 0.5% 6.8%Doxycycline 5 0 0.0% 0.0% 52.2%Bicillin 18 1 5.6% 0.1% 27.3%(Multiple) 2 0 0.0% 0.0% 84.2%All 151 4 2.6% 0.7% 6.6%

Treatment outcome

126 3 2.4%

Results: By HIV Status

Treated Failures Percent Treated Failures PercentTreatmentArithromycin 1GDoxycycline 4 0 0.0% none none noneBicillin 11 1 9.1% 6 0 0.0%(Multiple) 2 0 0.0% none none noneAll 103 3 2.9% 22 0 0.0%

HIV-negative HIV-positive

0 0.0%86 2 2.3% 16

Conclusions

• Failure rate for azithromycin was not significantly greater than rate for bicillin

• Since no resistance to bicillin has been documented, apparent treatment failures likely indicate re-exposure

• Success in treatment did not vary between HIV-negative and HIV-positive clients

Limitations

• No way to distinguish treatment failure from re-exposure

• Not all exposed will develop disease• No randomization

– penicillin allergies– field versus clinic

• Small number of follow-up titers• Wide confidence limits for negative results

Limitations

• No power to assess temporal trends– Azithromycin epi-treatment failures:

• November 2002

• April 2003

• July 2003

– Bicillin epi-treatment failure:• April 1999

Further research

• Another randomized trial of azithromycin vs. bicillin– HIV-positive clients only– San Francisco & Los Angeles– Five years later than 1999 study by Hook

Thank you ...