Margaret C. Snead

Detection of two biological markers of intercourse: prostate-specific antigen and Y-chromosomal DNA

BACKGROUND Although biological markers of womens exposure to semen from vaginal intercourse have been developed as surrogates for risk of infection or probability of pregnancy, data on their persistence time and clearance are limited. STUDY DESIGN During 2006-2008, 52 couples were enrolled for three 14-day cycles of abstinence from vaginal sex during which women were exposed in the clinic to a specific quantity (10, 100 or 1000 μL) of their partners semen. Vaginal swabs were collected before and at 1, 6, 12, 24, 48, 72 and 144 h after exposure for testing for prostate-specific antigen (PSA) and Y-chromosome DNA (Yc DNA). RESULTS Immediately after exposure to 1000 μL of semen, the predicted sensitivity of being PSA positive was 0.96; this decreased to 0.65, 0.44, 0.21 and 0.07 at 6, 12, 24 and 48 h, respectively. Corresponding predicted sensitivity of being Yc DNA positive was 0.72 immediately postexposure; this increased to 0.76 at 1 h postexposure and then decreased to 0.60 (at 6 h), 0.63 (at 12 h), 0.49 (at 24 h), 0.21 (at 48 h), 0.17 (at 72 h) and 0.12 (at 144 h). CONCLUSIONS Overall findings suggest that PSA may be more consistent as a marker of very recent exposure and that Yc DNA is more likely to be detected in the vagina after 12 h postexposure compared to PSA.

The Reproductive Health Behaviors of HIV-Infected Young Women in the United States: A Literature Review

HIV-infected young women in the United States have important reproductive health needs that are made more complex by their HIV status. We searched Pubmed and relevant bibliographies to identify 32 articles published from 2001 to July 2012 that described the prevalence, correlates, and characteristics of the sexual activity, relationships, pregnancy intentions, HIV status disclosure, and contraceptive and condom use among US HIV-infected adolescents and young women. Our synthesis of those articles found that, like youth not infected with HIV, substantial proportions of HIV-infected youth were sexually active, and most sought romantic or sexual relationships, though their serostatus may have affected the pace of physical and emotional intimacy. Disclosure was difficult, and large proportions of HIV-infected youth had not disclosed their serostatus to recent partners. A few studies suggest that most HIV-infected young women hoped to have children in the future, but many wanted to avoid pregnancy until later. Only one study described contraceptive use among this population in detail and found that condoms were a primary method of contraception. The results point to substantial gaps in published research, particularly in the areas of pregnancy intentions and contraceptive use. Much more needs to be done in research and health services to better understand and meet the complex health needs of HIV-infected young women.

Optimal methods for collecting and storing vaginal specimens for prostate-specific antigen testing in research studies☆

BACKGROUND Prostate-specific antigen (PSA) detected in vaginal fluid can be used in studies of HIV/sexually transmitted infection (STI) and pregnancy prevention as an alternative to relying on participant reports of exposure to semen. Optimal methods for collecting and storing specimens for this testing have not been determined. STUDY DESIGN We conducted a controlled, in vitro experiment of 550 specimens spiked with semen to determine the effects of swab type (five types), storage conditions of the swabs (room temperature with or without desiccant or at -80°C without desiccant) and time from collection to testing (seven intervals over the course of 12 months) on the identification of PSA. We performed factorial analysis of variance to identify factors influencing PSA detection. RESULTS Concentrations of PSA detected in the swabs declined with time of storage over the 1-year experiment (p<.01). The 1-mL, rayon-tipped swab stored immediately at -80°C following collection performed best. CONCLUSIONS If immediate testing or freezer storage is not feasible, investigators should use a swab with 1-mL capacity with processing and testing as soon as possible after specimen collection.

Prostate-specific antigen as a biomarker of condom failure: comparison of three laboratory assays and self-reported condom use problems in a randomized trial of female condom performance

BACKGROUND Prostate-specific antigen (PSA), a biomarker for semen exposure, may provide a more objective measure of condom failure than subject self-reports. Methods for measuring PSA vary and their comparability with respect to assessing condom performance has not been adequately evaluated. This study compared results from three different PSA assays of vaginal samples collected by subjects in a randomized clinical trial which compared the performance of female condoms. STUDY DESIGN We selected 30 pairs of pre- and post-coital vaginal samples from subjects who reported condom functionality problems or whose original PSA assay was positive. Samples were retested using three different PSA assays [quantitative enzyme-linked immunoassay (EIA), rocket immune-electrophoresis (RIE) and chromatographic immunoassay (CIA)]. We compared the proportion of condom uses where the post-coital PSA result indicated semen exposure for each of the three assays. RESULTS Despite varying levels of sensitivity, the results from all three assays were remarkably consistent. Self-reported condom failures did not correlate well with positive PSA results, suggesting that exclusive reliance on either PSA or user self-report may be inadequate for assessing condom functionality. CONCLUSION In combination with user self-report of condom failure, PSA testing provides a reliable, objective marker of condom functionality. Studies based on PSA testing may improve on conventional contraceptive clinical trials by offering a more direct assessment of a condom products ability to prevent semen exposure.

Effect of topical vaginal products on the detection of prostate-specific antigen, a biomarker of semen exposure, using ABAcards☆☆☆

BACKGROUND Prostate-specific antigen (PSA) is a biomarker of recent semen exposure. There is currently only limited information on whether topical vaginal products affect PSA assays. We investigated this question using various dilutions of several vaginal products (lubricants and spermicides) and the Abacus ABAcard for PSA detection. STUDY DESIGN Pooled semen controls and various dilutions of nonoxynol-9 (N9), carboxymethyl cellulose (CMC), Replens, Gynol 2, K-Y jelly, Astroglide, Surgilube, combined with pooled semen dilutions, were tested for PSA using the Abacus ABAcard. RESULTS N9 (2% with saline) and CMC did not appear to affect the results of testing with the ABAcard, but not all semen dilutions were tested. The other products (including Replens and Gynol, which is 2% N9 with propylene glycol, K-Y, Astroglide and Surgilube) at some of the dilutions tested either affected or gave invalid results with PSA testing using the ABAcard. Both Gynol 2 and K-Y at 1:10 dilution gave false-positive results. CONCLUSIONS Some vaginal products affect PSA results obtained by using the semiquantitative ABAcard. In vivo confirmation is necessary to further optimize PSA detection when topical vaginal products are present.

Recent Biomarker-Confirmed Unprotected Vaginal Sex, But Not Self-reported Unprotected Sex, Is Associated With Recurrent Bacterial Vaginosis.

Background Self-reported unprotected vaginal sex seems to increase risk of bacterial vaginosis (BV). However, the validity of self-reports is questionable, given their inconsistency with more objective measures of recent semen exposure such as detection of prostate-specific antigen (PSA). We examined whether recent unprotected sex, as measured both by PSA detection on vaginal swabs and by self-report, was associated with increased BV recurrence. Methods We analyzed randomized trial data from nonpregnant, BV-positive adult women recruited from a sexually transmitted disease clinic. Participants received BV therapy at enrollment and were scheduled to return after 4, 12, and 24 weeks. Bacterial vaginosis (by Nugent score) and PSA were measured at each visit. We used Cox proportional hazards models to examine the association between PSA positivity and recurrent BV. We also evaluated associations between self-reported unprotected sex (ever/never since the last visit and in the last 48 hours, analyzed separately) and recurrent BV. Results Prostate-specific antigen and BV results were available for 96 women who contributed 226 follow-up visits. Prostate-specific antigen positivity was associated with increased BV recurrence (adjusted hazard ratio [aHR], 2.32; 95% confidence interval [CI], 1.28–4.21). In contrast, we observed no significant increase in BV recurrence among women self-reporting unprotected sex since the last visit (aHR, 1.63; 95% CI, 0.77–3.43) or in the last 48 hours (aHR, 1.28; 95% CI, 0.70–2.36). Conclusions Estimates from earlier studies linking self-reported unprotected sex and BV may be biased by misclassification. Biomarkers can improve measurement of unprotected sex, a critical exposure variable in sexual health research.

Exploring Discordance Between Biologic and Self-Reported Measures of Semen Exposure: A Qualitative Study Among Female Patients Attending an STI Clinic in Jamaica

We explored the use of qualitative interviews to discuss discrepancies between two sources of information on unprotected sex: biomarker results and self-reported survey data. The study context was a randomized trial in Kingston, Jamaica examining the effect of STI counseling messages on recent sexual behavior using prostate-specific antigen (PSA) as the primary study outcome. Twenty women were interviewed. Eleven participants were selected because they tested positive for PSA indicating recent semen exposure, yet reported no unprotected sex in a quantitative survey (“discordant”): 5 reported abstinence and 6 reported condom use. Nine participants who also tested positive for PSA but reported unprotected sex in the survey were interviewed for comparison (“concordant”). Qualitative interviews with 6 of the 11 discordant participants provided possible explanations for their PSA test results, and 5 of those were prompted by direct discussion of those results. Rapid PSA testing combined with qualitative interviews provides a novel tool for investigating and complementing self-reported sexual behavior.

Relationship between social cognitive theory constructs and self-reported condom use: assessment of behaviour in a subgroup of the Safe in the City trial

Objectives Previous studies have found social cognitive theory (SCT)-framed interventions are successful for improving condom use and reducing sexually transmitted infections (STIs). We conducted a secondary analysis of behavioural data from the Safe in the City intervention trial (2003–2005) to investigate the influence of SCT constructs on study participants’ self-reported use of condoms at last intercourse. Methods The main trial was conducted from 2003 to 2005 at three public US STI clinics. Patients (n=38 635) were either shown a ‘safer sex’ video in the waiting room, or received the standard waiting room experience, based on their visit date. A nested behavioural assessment was administered to a subsample of study participants following their index clinic visit and again at 3 months follow-up. We used multivariable modified Poisson regression models to examine the relationships among SCT constructs (sexual self-efficacy, self-control self-efficacy, self-efficacy with most recent partner, hedonistic outcome expectancies and partner expected outcomes) and self-reported condom use at last sex act at the 3-month follow-up study visit. Results Of 1252 participants included in analysis, 39% reported using a condom at last sex act. Male gender, homosexual orientation and single status were significant correlates of condom use. Both unadjusted and adjusted models indicate that sexual self-efficacy (adjusted relative risk (RRa)=1.50, 95% CI 1.23 to 1.84), self-control self-efficacy (RRa=1.67, 95% CI 1.37 to 2.04), self-efficacy with most recent partner (RRa=2.56, 95% CI 2.01 to 3.27), more favourable hedonistic outcome expectancies (RRa=1.83, 95% CI 1.54 to 2.17) and more favourable partner expected outcomes (RRa=9.74, 95% CI 3.21 to 29.57) were significantly associated with condom use at last sex act. Conclusions Social cognitive skills, such as self-efficacy and partner expected outcomes, are an important aspect of condom use behaviour. Trial registration number clinicaltrials.gov (#NCT00137370).

A Quantitative Glycogen Assay to Verify Use of Self-Administered Vaginal Swabs

Background Self-administered swabs are used to sample vaginal contents for a variety of clinical purposes including detection of sexually transmitted infections, condom breakage, and vaginal product use. The goal of this study was to determine whether a quantitative glycogen assay can be used to assess whether a swab has been exposed to the vagina to assure study compliance. Study Design Buccal, skin, or vaginal samples were tested to determine whether a commercial quantitative glycogen assay can differentiate vaginal specimens. In addition, archived remnant de-identified vaginal swabs from clinical trials were tested. Periodic acid–Schiff stain was used to identify glycogen-positive cells as a confirmation test. Results Glycogen concentrations in eluates of vaginal swabs from reproductive-aged women were significantly higher than those from unused swabs (mean ± SE, 964 ± 135 &mgr;g/mL vs. 14.7 ± 2.5 &mgr;g/mL, P < 0.001) and swabs exposed to buccal and finger/hand epithelia (40.3 ± 4.8 and 18.5 ± 5.4 &mgr;g/mL, P < 0.001). Glycogen concentrations were lower and more variable in vaginal swabs from older perimenopausal/menopausal women (mean ± SE, 235 ± 123, P < 0.01). Semen and sample storage longer than 1 year did not affect glycogen detection. Using a cutoff of 100 &mgr;g/mL of glycogen, 30 of 30 vaginal swabs from reproductive-aged women versus 0 of 28 control swabs were positive, for an assay sensitivity of 1 (95% confidence interval, 0.86–1) and specificity of 1 (95% confidence interval, 0.85–1). Periodic acid–Schiff stain correlated with soluble glycogen results but was less specific. Conclusions The quantitative glycogen assay provides a simple and inexpensive method to validate the use of self-administered swabs for sampling vaginal contents in clinical studies.

Prevalence and risk factors associated with STIs among women initiating contraceptive implants in Kingston, Jamaica

Background There is limited information on rates of STIs in Jamaica due to syndromic management and limited aetiological surveillance. We examined the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) and characteristics associated with STIs among sexually active women who participated in a randomised trial of a progestin implant initiation in Jamaica (the Sino-Implant Study (SIS)). Methods SIS was a randomised trial conducted in Kingston, Jamaica, from 2012 to 2014 to evaluate whether initiation of the Sino-Implant (II) led to more unprotected sex among women ages 18–44 years. Data collected included self-reported demographic, sexual behaviour information; and vaginal swabs collected at baseline, 1-month and 3-month follow-up visits for a biomarker of recent semen exposure (prostate-specific antigen (PSA)) and for STIs. We examined associations between STIs and PSA, demographics, sexual behaviour and insertion of an implant, with a repeated-measures analysis using generalised estimating equations (SAS Institute, V.9.3). Results Remnant vaginal swabs from 254 of 414 study participants were tested for STIs. At baseline, 29% of participants tested for STIs (n=247) had laboratory-confirmed CT, 5% NG, 23% TV and 45% any STI. In a repeated-measures analysis adjusted for study arm (immediate vs delayed implant insertion), those with PSA detected did not have an increased prevalence of any STI (prevalence ratio (PR)=1.04 (95% CI 0.89 to 1.21)), whereas prevalence decreased for each 1-year increase in age (PR=0.98 (95% CI 0.97 to 0.99)). Immediate implant insertion was not associated with increases in any STI in subsequent visits (PR=1.09 (95% CI 0.94 to 1.27)). Conclusions Although the prevalence of laboratory-confirmed STIs was high, the immediate initiation of a contraceptive implant was not associated with higher STI prevalence rates over 3 months. Trial registration number NCT01684358.