Comparison of self-reported female condom failure and biomarker-confirmed semen exposure.

OBJECTIVE: To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. STUDY DESIGN: We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected precoital and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. RESULTS: Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p=.03). Of the 207 WC efficacy uses with evaluable postcoital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. CONCLUSIONS: When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. IMPLICATIONS: Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.

Effects of initiating a contraceptive implant on subsequent condom use: A randomized controlled trial.

OBJECTIVE: To evaluate whether initiation of a contraceptive implant, a method of long-acting reversible contraception, reduces condom use, as measured by a biomarker of recent semen exposure [prostate-specific antigen (PSA)]. STUDY DESIGN: We conducted a randomized controlled clinical trial in which 414 Jamaican women at high risk for sexually transmitted infections (STIs) attending family planning clinics received the contraceptive implant at baseline ("immediate" insertion arm, N=208) or at the end ("delayed" insertion arm, N=206) of a 3-month study period. Participants were tested for PSA at baseline and two follow-up study visits and were asked about their sexual activity and condom use. RESULTS: At baseline, 24.9% of women tested positive for PSA. At both follow-up visits, the prevalence of PSA detection did not significantly differ between the immediate versus delayed insertion arm [1-month: 26.1% vs. 20.2%, prevalence ratio (PR)=1.3, 95% confidence interval (CI)=0.9-1.9; 3-month: 25.6% vs. 23.1%, PR= 1.1, 95% CI=0.8-1.6]. The change in PSA positivity over the three study visits was not significantly larger in the immediate arm compared to the delayed arm (1-sided p-value of .15). CONCLUSIONS: Contraceptive implants can be successfully introduced into a population at high risk of unintended pregnancy and STIs without a biologically detectable difference in unprotected sex in the short term. This information strengthens the evidence to support promotion of implants in such populations and can help refine counseling for promoting and maintaining use of condoms among women who choose to use implants. IMPLICATIONS: Sex unprotected by a condom was not higher over 3 months in women receiving a contraceptive implant, compared with those not receiving the implant.

Does tenofovir gel or do other microbicide products affect detection of biomarkers of semen exposure in vitro?

OBJECTIVES: There is currently no information on whether products evaluated in HIV microbicide trials affect the detection of the semen biomarkers prostate-specific antigen (PSA) or Y chromosome DNA. STUDY DESIGN: We tested (in vitro) dilutions of tenofovir (TFV), UC781 and the hydroxyethylcellulose (HEC) placebo gels using the Abacus ABAcard and the quantitative (Abbott Architect total PSA) assays for PSA and Y chromosome DNA by real-time polymerase chain reaction. RESULTS: TFV gel and the HEC placebo adversely affected PSA detection using the ABAcard but not the Abbott Architect total PSA assay. UC781 adversely affected both the ABAcard and Abbott Architect total PSA assays. While there were some quantitative changes in the magnitude of the signal, none of the products affected positivity of the Y chromosome assay. CONCLUSIONS: The presence of TFV or HEC gels did not affect quantitative PSA or Y chromosome detection in vitro. Confirmation of these findings is recommended using specimens obtained following use of these gels in vivo. IMPLICATIONS: Researchers should consider the potential for specific microbicides or any products to affect the particular assay used for semen biomarker detection. The ABAcard assay for PSA detection should not be used with TFV UC781, or HEC.

Effect of lubricants and a vaginal spermicide gel on the detection of prostate specific antigen, a biomarker of semen exposure, using a quantitative (Abbott ARCHITECT) assay.

OBJECTIVES: Little is known about the effects of commonly used lubricants on detection of biomarkers of semen exposure. We investigated the in vitro effect of Gynol®, K-Y Jelly®, Replens®, Astroglide®, Carbopol, and Silicorel on quantitative detection of prostate specific antigen (PSA). STUDY DESIGN: A predetermined concentration of each of the gels was added to serially diluted semen samples. Additionally, serial dilutions of each of the gels were added to three different semen dilutions (high, medium, or low). The resulting samples were tested for PSA on the Abbott ARCHITECT System. RESULTS: When using the Abbott ARCHITECT system, the only products that inhibited PSA detection were Gynol® and Replens®. The inhibition caused by Gynol® was dose-dependent, but that of Replens was dose-independent. K-Y Jelly®-spiked samples had higher PSA values than controls. CONCLUSIONS: Caution is warranted when using the Abbott quantitative assay for PSA detection as a biomarker of semen exposure in settings where Gynol®, Replens® or K-Y Jelly® might also have been used. Neither Astroglide® nor Silicorel inhibited PSA detection. Additional studies evaluating other vaginal products, including microbicides, and their effects on other assays, are needed. In vivo studies will be especially important to optimize PSA detection from clinical samples. IMPLICATIONS: Researchers should consider the potential for specific lubricants or any vaginal products to affect the particular assay used for semen biomarker detection. The Abbott ARCHITECT's total PSA assay should not be used with the product Replens. Caution is warranted when using the assay in settings where Gynol or K-Y jelly may have been used.

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.

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.

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.

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 µg/mL vs. 14.7 ± 2.5 µg/mL, P < 0.001) and swabs exposed to buccal and finger/hand epithelia (40.3 ± 4.8 and 18.5 ± 5.4 µg/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 µg/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.