Rate of Decline in Nontreponemal Antibody Titers and Seroreversion After Treatment of Early Syphilis.

BACKGROUND: Syphilis management is complex and demonstration of treatment response requires monitoring of nontreponemal antibody titers for a ≥ 4-fold decline and/or seroreversion to nonreactive titers. METHODS: We evaluated data from a multicenter clinical trial of syphilis treatment conducted from 2000 to 2009 involving human immunodeficiency virus (HIV)-negative patients 18 years or older with early syphilis. To assess the rate of titer decline and seroreversion after effective therapy, rapid plasma reagin (RPR) titers were analyzed at 1, 3, 6, 9, and 12 months among patients with an appropriate treatment response. We plotted the rate of RPR titer decline after treatment, estimated the frequency of seroreversion, and conducted multivariate analyses to assess characteristics associated with seroreversion. RESULTS: Among 369 (79.4%) of 465 HIV-negative patients with early syphilis who had an appropriate treatment response, 333 participants had complete RPR data over 12 months. Although the decline in RPR titers was ≥ 4-fold among 88.0% (293/333) of participants at 3 months and ≥ 8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy. Male sex (adjusted odds ratio, 4.3; 95% confidence interval, 1.8-10.5) and baseline RPR titers ≤ 1:32 (adjusted odds ratio, 14.5; 95% confidence interval, 6.8-31.2) were associated with higher odds of seroreversion compared with females and titers > 1:32, respectively. CONCLUSIONS: Despite a ≥ 4-fold RPR titer decline after treatment, the majority of HIV-negative patients with early syphilis failed to have seroreversion at 12 months. Nontreponemal antibody titers often persist despite an appropriate treatment response.

Prevalence and treatment outcome of cervicitis of unknown etiology.

BACKGROUND: Mucopurulent cervicitis (MPC) is a clinical syndrome characterized by mucopurulent discharge from the cervix and other signs of inflammation. This was a phase III, multicenter study designed to evaluate the effectiveness of placebo versus empiric antibiotic treatment for clinical cure of MPC of unknown etiology at 2-month follow-up. Unfortunately, enrollment was terminated because of low accrual of women with cervicitis of unknown etiology, but important prevalence and outcome data were obtained. METHODS: Five hundred seventy-seven women were screened for MPC. Women with MPC were randomized to the treatment or placebo arm of the study, and the 2 arms were evaluated based on the etiology, clinical cure rates, adverse events (AEs), and rates of pelvic inflammatory disease. RESULTS: One hundred thirty-one (23% [131/577]) screened women were found to have MPC. Eighty-seven were enrolled and randomized. After excluding women with sexually transmitted infections and other exclusions, 61% (53/87) had cervicitis of unknown etiology. The overall clinical failure rate was 30% (10/33), and the clinical cure rate was only 24% (8/33). Rates were not significantly different between the arms. There were 24 gastrointestinal AEs in the treatment arm compared with 1 AE in the placebo arm. CONCLUSIONS: More than half of the cases of MPC were of unknown etiology. Clinical cure rates for the placebo and treatment arms were extremely low, with most women concluding the study with a partial response. Gastrointestinal AEs were higher in the treatment arm.

Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin.

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus-negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up.

Rapid plasma reagin titer variation in the 2 weeks after syphilis therapy.

BACKGROUND: Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. METHODS: Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory. RESULTS: Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. CONCLUSIONS: Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.

Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis.

BACKGROUND: Syphilis management requires serological monitoring after therapy. We compared factors associated with serological response after treatment of early (ie, primary, secondary, or early latent) syphilis. METHODS: We performed secondary analyses of data from a prospective, randomized syphilis trial conducted in the United States and Madagascar. Human immunodeficiency virus (HIV)-negative participants aged ≥ 18 years with early syphilis were enrolled from 2000-2009. Serological testing was performed at baseline and at 3 and 6 months after treatment. At 6 months, serological cure was defined as a negative rapid plasma reagin (RPR) test or a ≥4-fold decreased titer, and serofast status was defined as a ≤ 2-fold decreased titer or persistent titers that did not meet criteria for treatment failure. RESULTS: Data were available from 465 participants, of whom 369 (79%) achieved serological cure and 96 (21%) were serofast. In bivariate analysis, serological cure was associated with younger age, fewer sex partners, higher baseline RPR titers, and earlier syphilis stage (P ≤ .008). There was a less significant association with Jarisch-Herxheimer reaction after treatment (P = .08). Multivariate analysis revealed interactions between log-transformed baseline titer with syphilis stage, in which the likelihood of cure was associated with increased titers among participants with primary syphilis (adjusted odds ratio [AOR] for 1 unit change in log(2) titer, 1.83; 95% confidence interval [CI], 1.25-2.70), secondary syphilis (AOR, 3.15; 95% CI, 2.14-4.65), and early latent syphilis (AOR, 1.86; 95% CI, 1.44-2.40). CONCLUSIONS: Serological cure at 6 months after early syphilis treatment is associated with age, number of sex partners, Jarisch-Herxheimer reaction, and an interaction between syphilis stage and baseline RPR titer.

A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.

BACKGROUND: Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy. METHODS: This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly. RESULTS: A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints. CONCLUSIONS: In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.

Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria.

BACKGROUND: This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection. METHODS: This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1:1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events. RESULTS: The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3-1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5-1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported. CONCLUSIONS: Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120770.

Does a choice of condoms impact sexually transmitted infection incidence? A randomized, controlled trial.

OBJECTIVE: The objective of this study was to assess whether providing a choice of condoms would increase condom acceptability, increase self-reported use, and decrease incident sexually transmitted infection. STUDY: We randomized 414 men presenting with urethral discharge in Jamaica to receive either the "standard" clinic condom or a choice of 4 different types of condoms. Men were treated presumptively at enrollment and followed up at 1, 2, 4, and 6 months. RESULTS: Participants in the choice group had a strong preference (P <0.01) for the most popular condom available in Jamaica. This preference did not translate into higher condom use (P = 0.16). The 6-month cumulative probability of first incidence of gonorrhea, chlamydia, or trichomoniasis was slightly higher in the choice group (21%; 95% confidence interval [CI], 15-28%) versus the control group (17%; 95% CI, 11-23%); the difference in the survival curves was not significant (P = 0.35). CONCLUSION: A choice of condoms may increase perceived acceptability but not lead to increased condom use and subsequently lower sexually transmitted infection rates.