Comparisons and correlations of 1-month recall vs 24-hour recall in patient-reported outcomes of an exploratory, phase 2b, randomized, double-blind, placebo-controlled clinical trial of sildenafil cream, 3.6% for the treatment of female sexual arousal disorder.

BACKGROUND: Efficacy assessments in clinical trials of treatments for female sexual arousal disorder (FSAD) and other female sexual dysfunction (FSD) diagnoses rely on various patient-reported outcomes (PROs). AIMS: We sought to compare 1-month recall PRO measures among participants enrolled in a clinical trial who provided these data without (test population) vs with (control population) use of an at-home, 24-hour recall electronic diary (eDiary), capturing similar data. METHODS: Preplanned subset analysis as performed during a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD. Preliminary product efficacy was assessed via 1-month recall and 24-hour recall questionnaires. A subset of the participants, the Evaluation of Recall Subset [ERS] provided PROs via the 1-month recall instruments but did not provide data via the 24-hour recall eDiary. OUTCOMES: Responses to the 1-month recall instruments were compared among ERS (test) vs non-ERS (control) participants. Among the non-ERS population, correlations between 1-month and 24-hour recall endpoints were calculated. RESULTS: There were no significant differences in the study co-primary 1-month recall efficacy endpoints, the Arousal Sensation (AS) domain of the 28-item Sexual Function Questionnaire (SFQ28) and the Female Sexual Distress Scale - Desire, Arousal, Orgasm question 14, among ERS vs non-ERS participants during the initial 1-month no-drug run-in period or the 1-month single-blind placebo run-in period (P values > .47). Scores on these 1-month recall PROs continued to be similar after randomization for sildenafil cream (P values > .30) and placebo cream (P values > .20) assigned ERS and non-ERS participants during the 3-month double-blind dosing period. There were strong correlations between the SFQ28 AS and eDiary AS scores during the no-drug run-in (R = 0.79, P < .01) and the single-blind run-in (R = 0.73 P < .001). During the double-blind dosing period, the SFQ28 AS score continued to be highly correlated with the eDiary AS score among sildenafil cream users (R = 0.83; P < .001) and placebo cream users (R = 0.8; 2 P < .001). CLINICAL IMPLICATIONS: There was no evidence that 1-month recall PRO instruments introduce recall bias; assessing arousal sensations with 24-hour vs 1-month PRO instruments is similar and either method could be used to assess efficacy depending on study objectives. STRENGTHS AND LIMITATIONS: This preplanned subset analysis compared efficacy of PROs based on recall duration. While the subset was preplanned, the study was powered to detect significant differences in the primary efficacy objectives, not among this subset analyses. CONCLUSION: These data will be used in planning future efficacy assessments of sildenafil cream for FSAD. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with ClinicalTrials.gov, NCT04948151.

Comparison of visual and ultraviolet light inspection versus DNA/protein biomarkers to assess product adherence with vaginal microbicide applicators.

BACKGROUND: Objective biomarkers of product use and protocol compliance are urgently needed. We compared the sensitivity and specificity of DNA and protein-based biomarkers, obtained from used vaginal gel applicators, to visual inspection of those applicators under ambient light (visual inspection of returned applicator [VIRA]) and ultraviolet light (UVL). METHODS: Forty women inserted hydroxyethylcellulose placebo gel vaginal applicators under direct observation. Applicators were evaluated by VIRA, UVL, and DNA/protein-based methods at 2 time points: within 7 days of the visit and after storing applicators for approximately 30 days. Semen biomarkers were assayed from vaginal swabs and returned applicators. RESULTS: The overall sensitivity and specificity of DNA and protein-based biomarkers in determining vaginal insertion versus sham handling of returned applicators were 98.3% and 100%, respectively, at both 7- and 30-day evaluations. The overall sensitivity and specificity of VIRA at 7 and 30 days after collection were significantly lower than those of DNA and protein-based biomarkers. Ultraviolet light inspection also had significantly lower overall sensitivity and overall specificity compared with DNA and protein biomarkers. The sensitivity of DNA and protein-based biomarkers for detecting insertion of wiped applicators was 95%, whereas the sensitivity of VIRA (range of 24%-28%) and UVL inspection (range, 38%-84%) was low for this subset. It was feasible to obtain semen biomarkers from vaginal swabs and returned used applicators. CONCLUSIONS: DNA and protein-based biomarkers offer significantly higher sensitivity and specificity compared with VIRA and UVL assessment. The accuracy of these objective biomarkers is maintained despite storage of returned products for approximately 30 days and under conditions potentially modeling field use.

Preliminary Efficacy of Topical Sildenafil Cream for the Treatment of Female Sexual Arousal Disorder: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder. METHODS: We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale-Desire, Arousal, Orgasm). RESULTS: Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P =.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores. This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P ≤.04). CONCLUSION: Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction. In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04948151.

Multipurpose prevention technologies: biomedical tools to prevent HIV-1, HSV-2, and unintended pregnancies.

Statistics clearly show an unmet need for highly effective contraception, especially in less developed countries. Many of these countries are at the core of the HIV/AIDS epidemic and show very high prevalence rates for other sexually transmitted infections (STIs) such as that caused by HSV-2. A woman at risk of unintended pregnancy due to unprotected intercourse is also at risk for HIV/STI. Owing to their causative interrelationship, combining protection against these conditions will result in enhanced prevention and health benefits. Existing multipurpose prevention modalities such as condoms and physical barriers, albeit efficacious, face cultural hurdles that have so far hindered their widespread use. Success has recently been demonstrated in large clinical trials, demonstrating proof of concept of microbicides in reducing the incidence of HIV-1 and HSV-2 among at-risk populations. The challenge heretofore is to refine these products to make them more potent, convenient, accessible, and acceptable. Potent antiviral drugs released topically in the female reproductive tract by innovative delivered systems and formulations will provide safe, effective, and acceptable multipurpose prevention tools. This paper provides an overview of existing and novel approaches to multipurpose prevention strategies.

An alternative monitoring protocol for single-dose methotrexate therapy in ectopic pregnancy.

OBJECTIVE: We sought to determine the sensitivity and specificity of alternative monitoring regimens in predicting the need for a second methotrexate (MTX) dose in women undergoing medical therapy for ectopic pregnancy. STUDY DESIGN: We reviewed 187 women who received MTX for ectopic pregnancy. RESULTS: We defined MTX treatment success as a clinically stable patient whose day-7 beta human chorionic gonadotropin (beta-hCG) level decreased by > or = 50%, compared with the day-of-treatment (DOT) beta-hCG. In comparison to the standard MTX monitoring protocol, this model was 100% sensitive and 57.4% specific in predicting the need for a second MTX dose in women whose DOT beta-hCG was <2000 mIU/mL and was 100% sensitive and 37.9% specific in women whose DOT beta-hCG was > or = 2000 mIU/mL. CONCLUSION: This model is an alternative to the traditional MTX monitoring regimen.

The male sexual partners of adult versus teen women with sexually transmitted infections.

OBJECTIVES: We compared the male sexual partners of teen girls of age 15 to 19 years, currently infected with a sexually transmitted infection (STI) versus the male partners of adult women of age 20 to 41 years, with an STI to determine risk factors in these high-risk sexual dyads related to the male partner. STUDY DESIGN: Interview of 514 men who were partnered with 152 teen girls and 362 adult women, enrolled in Project Sexual Awareness for Everyone, a randomized controlled trial of behavioral intervention to reduce recurrent STIs. RESULTS: Compared to the male partners of adult women, male partners of teen girls were significantly more likely (P < 0.05) to be infected with any STI at intake. Men partnered with teens were younger and had significantly more sexual partners per year sexually active, shorter relationship length, and shorter length of monogamy with the index girls. They were more likely to report that it was "really important" for the teen to have their baby (P = 0.04) and were slightly more likely to be the father of her children (P = 0.17). Young age independently predicted STI infection in men. CONCLUSIONS: Although all women had an STI at intake, important differences were noted among the male partners of teens versus adults. Clinicians with similar populations may use this data to understand the characteristics of male partners of teens with STIs, in order to more effectively counsel adult and teen women on partner notification, treatment and STI prevention.

Effect of acculturation on the acceptability of potential microbicides and sexual risk-taking.

BACKGROUND: The objective was to determine the acceptability and use patterns of potential microbicides among African American (AA), acculturated Hispanic (AH), and less acculturated Hispanic (LAH) women. We measured baseline sexual risk-taking and the likelihood of behavioral change, given effective microbicides. METHODS: Interview of 506 Mexican-American and AA women, all of whom have a sexually transmitted infection enrolled in Project Sexual Awareness for Everyone. RESULTS: The 3 groups reported similarly high acceptance of potential microbicides (76%-83% P = 0.24). LAHs were most likely to report they would use microbicides covertly (P = 0.03). Given the possibility of effective microbicides, AHs were consistently more likely to report risk disinhibition. AHs, as compared to LAHs and AAs, respectively, were most likely to report that they would not use condoms, (53% vs. 33% vs. 30% P <0.001), would have a 1-night stand (18% vs. 8% vs. 6% P = 0.02), or would have sex with humans before they got to know them (18% vs. 8% vs. 6% P = 0.01). AHs were also most likely to say they would or probably would change from baseline safe sexual practices to unsafe sexual behaviors if potential microbicides were available. Age was controlled for in the analysis as AHs were younger than AAs and LAHs. CONCLUSIONS: Future microbicides were acceptable among this at risk cohort. Acculturation was a predictor of risk disinhibition and should be considered when tailoring sexually transmitted infection prevention messages, given the advent of effective microbicides.

Unfulfilled postpartum sterilization requests.

OBJECTIVE: To determine individual and delivery characteristics of women least likely to obtain a requested postpartum tubal ligation (PPTL) and, secondarily, to compare the postpartum contraceptive choices of women with an unfulfilled sterilization request to women not requesting a PPTL. STUDY DESIGN: Record review ofwomen delivering a liveborn singleton between December 2007 and May 2008 at the University of Texas San Antonio. Primary outcomes were risk factors for not receiving a requested PPTL. Secondary outcome was to compare the postpartum contraceptive choices of women not receiving a PPTL to controls, women not requesting a PPTL. RESULTS: During the observation period, 429 of 1,460 women requested a PPTL; 296 (69%) received the procedure, and 133 (31%) did not. The majority of patients (332/429, 77.4%) were Hispanic. Pretest power analysis concluded that 107 women were required in each group. Cesarean delivery was associated with the highest likelihood of receiving a PPTL. Women receiving a PPTL were more likely (p < or = 0.05) to be a documented U.S. resident, married, of lower parity, have private or any medical insurance and to have received any prenatal care. Postpartum contraception among women with unfulfilled sterilization requests was similar to that among controls. CONCLUSION: Although financial and policy barriers exist, the majority of patients requesting a PPTL received the procedure.

Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/levonorgestrel vaginal rings.

Recent data support that the vaginal microbiota may alter mucosal pharmacokinetics (PK) of topically delivered microbicides. Our team developed an intravaginal ring (IVR) that delivers tenofovir (TFV) (8-10 mg/day) alone or with levonorgestrel (LNG) (20 ug/day). We evaluated the effect of IVRs on the vaginal microbiota, and describe how the vaginal microbiota impacts mucosal PK of TFV. CONRAD A13-128 was a randomized, placebo controlled phase I study. We randomized 51 women to TFV, TFV/LNG or placebo IVR. We assessed the vaginal microbiota by sequencing the V3-V4 regions of 16S rRNA genes prior to IVR insertion and after approximately 15 days of use. We measured the concentration of TFV in the cervicovaginal (CV) aspirate, and TFV and TFV-diphosphate (TFV-DP) in vaginal tissue at the end of IVR use. The change in relative or absolute abundance of vaginal bacterial phylotypes was similar among active and placebo IVR users (all q values >0.13). TFV concentrations in CV aspirate and vaginal tissue, and TFV-DP concentrations in vaginal tissue were not significantly different among users with community state type (CST) 4 versus those with Lactobacillus dominated microbiota (all p values >0.07). The proportions of participants with CV aspirate concentrations of TFV >200,000 ng/mL and those with tissue TFV-DP concentrations >1,000 fmol/mg were similar among women with anaerobe versus Lactobacillus dominated microbiota (p = 0.43, 0.95 respectively). There were no significant correlations between the CV aspirate concentration of TFV and the relative abundances of Gardnerella vaginalis or Prevotella species. Tissue concentrations of TFV-DP did not correlate with any the relative abundances of any species, including Gardnerella vaginalis. In conclusion, active IVRs did not differ from the placebo IVR on the effect on the vaginal microbiota. Local TFV and TFV-DP concentrations were high and similar among IVR users with Lactobacillus dominated microbiota versus CST IV vaginal microbiota. Trial registration: ClinicalTrials.gov NCT02235662.

Methicillin-resistant Staphylococcus aureus as a common cause of vulvar abscesses.

OBJECTIVE: To estimate the incidence of methicillin-resistant Staphylococcus aureus (MRSA) among women with vulvar abscesses and to describe clinical factors associated with inpatient compared with outpatient treatment. METHODS: We reviewed all women with a vulvar abscess who were treated with incision and drainage between October 2006 to March 2008. We reviewed the abscess cultures and evaluated clinical and laboratory variables associated with inpatient compared with outpatient treatment. RESULTS: During the 80-week study period, 162 women were treated for a vulvar abscess. Methicillin-resistant S aureus was isolated from 85 of 133 (64%) cultured vulvar abscesses. No presenting signs or symptoms were more common among patients with MRSA abscesses. Women with an MRSA vulvar abscess were not more likely to require inpatient admission or experience treatment complications. Inpatient treatment occurred in 64 of 162 (40%) patients and was predicted by medical comorbidities: diabetes (45.3%, odds ratio [OR] 2.29, 95% confidence interval [CI] 1.12-4.72), hypertension (34.4%, OR 2.33, 95% CI 1.06-5.13), initial serum glucose greater than 200 (37.5%, OR 3.32, 95% CI 1.48-7.51), and signs of worse infection, ie, larger abscesses (mean 5.2 cm) (P<.001) and elevated white blood cell count of at least 12,000/mm3 (45.3%, OR 3.04, 95% CI 1.44-6.43). CONCLUSION: Methicillin-resistant S aureus was the most common organism isolated from vulvar abscesses. Inpatient treatment is more common in women with medical comorbidities, larger abscesses, and signs of systemic illness. An antibiotic regimen with activity against MRSA, such as trimethoprim-sulfamethoxazole, should be considered in similar populations with vulvar abscesses.

Preventing recurrent sexually transmitted diseases in minority adolescents: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of a randomized controlled trial of the Sexual Awareness For Everyone (SAFE) behavioral intervention on teenagers (aged 14 to 18 years) compared with adult rates of reinfection with Neiserria gonorrhea or Chlamydia trachomatis cervicitis, and to identify behaviors associated with recurrent infection. METHODS: Mexican-American and African-American females with a nonviral sexually transmitted disease (STD) were enrolled in SAFE or assigned to the control group. All participants were interviewed and examined at baseline, 6, and 12 months. The primary outcome variable was reinfection with N. gonorrhea or C. trachomatis. Secondary outcomes were changes in risky sexual behavior. RESULTS: Teens randomized to participation in SAFE had a statistically lower incidence of recurrent N. gonorrhea and C. trachomatis at 0 to 6 months (52%, P=.04) and cumulatively (39%, P=.04) compared with teens in the control group. Cumulatively, teens as a group had higher rates of reinfection (33.1%) than adults (14.4%) (P<.001). Adolescent reinfection was explained by unprotected sex with untreated partners (adjusted odds ratio [OR] 5.58), nonmonogamy (adjusted OR 5.14), and rapid partner turnover (adjusted OR 2.02). In adults, reinfection was predicted by unprotected sex with untreated partners (adjusted OR 4.90), unsafe sex (adjusted OR 2.18), rapid partner turnover (adjusted OR 3.13), and douching after sex (adjusted OR 2.14). CONCLUSION: Sexual Awareness for Everyone significantly reduced recurrent STDs in teenagers. Adults and teens randomized to the SAFE intervention had significant decreases in high-risk sexual behaviors as compared with those in the control group. Although not specifically designed for teens, the SAFE intervention worked very well in this high-risk population. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, ClinicalTrials.gov, HSC2004415H. LEVEL OF EVIDENCE: I.

Partner notification of sexually transmitted infections among pregnant women.

The object of this study was to determine the factors associated with partner notification (PN) of sexually transmitted infection (STI) exposure among pregnant, low income, Mexican-American (MA) and African-American (AA) women and their male sexual partners. We used a cross-sectional analysis of 166 pregnant women with an STI, enrolled in a randomized controlled trial of behavioural intervention to prevent recurrent STIs. The primary outcome, PN, is notification of, or intent to notify male sexual partner(s) of STI exposure. Pregnant women with one (n = 136) versus multiple (n = 30) partners reported PN for 88.2% and 54.5% of male partners, respectively (P < 0.001). Multivariate logistic regression demonstrated three variables that independently predicted PN: a steady relationship, with one male sexual partner and recent (<30 days) intercourse with the partner. Among the low income, pregnant MA and AA women, the three relationship variables predicted 81.6% of PN and correctly classified 78.5% of males notified and 65.7% of males not notified.

Differences in Local and Systemic TFV PK Among Premenopausal Versus Postmenopausal Women Exposed to TFV 1% Vaginal Gel.

OBJECTIVE: We describe and compare the local and systemic pharmacokinetics (PK) of tenofovir (TFV) and TFV-diphosphate (TFV-DP) in healthy premenopausal (PRE) and postmenopausal (POST) women using TFV 1% gel and correlate local PK with other mucosal end points. METHODS: PRE (n = 20) and POST (n = 17) women used 2 doses of TFV 1% vaginal gel, separated by 2 hours. Blood and cervicovaginal samples were obtained 3 and 23 hours after the second dose. PRE women used gel in the follicular and luteal phases of the menstrual cycle. POST women used gel at baseline and again after approximately 2 months of treatment with 0.01% vaginal estradiol (E2) cream. RESULTS: Median TFV concentrations in cervicovaginal aspirate (ng/mL) and vaginal tissue (ng/mg) were significantly higher in PRE (4.3E10, 49.8) versus POST women (2.6E10, 2.2). POST women had significantly higher median molecular ratios of TFV-DP to TFV (3.7%) compared with PRE (0.19%). After vaginal E2 treatment, the local and systemic PK end points in POST women were generally similar to PRE women (all P values > 0.05). Importantly, median vaginal tissue TFV-DP concentrations (fmol/mg) among PRE, POST, and POST women after E2 therapy were similar (292.5, 463.3, and 184.6, respectively). Vaginal tissue TFV concentrations were significantly positively correlated with vaginal epithelial thickness, whereas vaginal tissue TFV-DP concentrations were positively correlated with density of vaginal CD4 and CD8 immune cells. CONCLUSIONS: The state of the cervicovaginal mucosa has a significant impact on local and systemic PK of a topically applied microbicide.

Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women.

To prevent the global health burdens of human immunodeficiency virus [HIV] and unintended/mistimed pregnancies, we developed an intravaginal ring [IVR] that delivers tenofovir [TFV] at ~10mg/day alone or with levonorgestrel [LNG] at ~20µg/day for 90 days. We present safety, pharmacokinetics, pharmacodynamics, acceptability and drug release data in healthy women. CONRAD A13-128 was a randomized, placebo controlled phase I study. We screened 86 women; 51 were randomized to TFV, TFV/LNG or placebo IVR [2:2:1] and 50 completed all visits, using the IVR for approximately 15 days. We assessed safety by adverse events, colposcopy, vaginal microbiota, epithelial integrity, mucosal histology and immune cell numbers and phenotype, cervicovaginal [CV] cytokines and antimicrobial proteins and changes in systemic laboratory measurements, and LNG and TFV pharmacokinetics in multiple compartments. TFV pharmacodynamic activity was measured by evaluating CV fluid [CVF] and tissue for antiviral activity using in vitro models. LNG pharmacodynamic assessments were timed based on peak urinary luteinizing hormone levels. All IVRs were safe with no significant colposcopic, mucosal, immune and microbiota changes and were acceptable. Among TFV containing IVR users, median and mean CV aspirate TFV concentrations remained above 100,000 ng/mL 4 hours post IVR insertion and mean TFV-diphosphate [DP] concentrations in vaginal tissue remained above 1,000 fmol/mg even 3 days post IVR removal. CVF of women using TFV-containing IVRs completely inhibited [94-100%] HIV infection in vitro. TFV/LNG IVR users had mean serum LNG concentrations exceeding 300 pg/mL within 1 hour, remaining high throughout IVR use. All LNG IVR users had a cervical mucus Insler score <10 and the majority [95%] were anovulatory or had abnormal cervical mucus sperm penetration. Estimated in vivo TFV and LNG release rates were within expected ranges. All IVRs were safe with the active ones delivering sustained high concentrations of TFV locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. The TFV and TFV/LNG rings are ready for expanded 90 day clinical testing. Trial registration ClinicalTrials.gov #NCT02235662.

Chronic endometritis in DMPA users and Chlamydia trachomatis endometritis.

OBJECTIVE: This study was conducted to determine the prevalence of Chlamydia trachomatis (CT) in the endometrium of depot medroxyprogesterone acetate (DMPA) users with and without breakthrough bleeding (BTB) (unscheduled bleeding) and/or chronic endometritis (CE). METHODS: Cross-sectional study. Endometrial biopsies were performed on 20 DMPA users who were having BTB and 20 DMPA users who were amenorrheic. The paraffin-embedded tissue sections were washed with xylene and ethanol to remove the paraffin. CT was identified in the endometrial samples using the COBAS AMPLICOR (Roche Diagnostics, Branchburg, NJ, USA) polymerase chain reaction (PCR) identification system. RESULTS: Chronic endometritis was the most common histologic finding (10/40, 25%) and occurred more often in women experiencing BTB (35% vs. 15%) (RR 1.62, CI 0.91-2.87). No patient with CE had CT infection of the endometrium or cervix. CONCLUSIONS: CT was not a cause of CE in this population of at-risk patients using DMPA. It is possible that CE in DMPA users reflects an inflammatory state, a function of an atrophic endometrium. This points to the possibility of nonsteroidal anti-inflammatory drugs as therapy for CE in this population rather than antimicrobials or hormonal medication.

Preventing repeat teen pregnancy: postpartum depot medroxyprogesterone acetate, oral contraceptive pills, or the patch?

STUDY OBJECTIVE: To prospectively evaluate the repeat teen pregnancy rates, within one year of delivery, among adolescents who choose the contraceptive patch (Ortho Evra) versus oral contraceptive pills (OCP) versus Depot Medroxyprogesterone Acetate (Depo Provera, DMPA) for postpartum contraception. DESIGN: Observational, prospective cohort study. Comparison groups are postpartum teens, who self-select the contraceptive patch (n = 55) versus DMPA (n = 142) versus OCPs (n = 55) immediately postpartum. SETTING: Medical University of South Carolina, a tertiary medical center. PARTICIPANTS: Postpartum teens, 11-19 years old; 72% were African American, and 96% qualified for Medicaid insurance. INTERVENTIONS: A structured telephone interview was performed every 3 months. MAIN OUTCOME MEASURES: The primary outcome measure was a repeat pregnancy within 12 months of the index delivery. Secondary outcome variables were contraceptive continuation rates, reasons for discontinuation, side effects and condom usage. RESULTS: At 1-year follow-up, repeat pregnancy rates were 14.2%, 29.7%, and 31.8% among DMPA, OCP, and patch users respectively (P = 0.02). DMPA users were significantly more likely to be using any form of hormonal contraception 1 year postpartum than patch or OCP users. Condom use was similarly low among all cohorts. CONCLUSION: Adolescents who choose DMPA for postpartum contraception are significantly less likely to become pregnant within 1 year of delivery, as compared to teens who choose OCPs or the patch.

Analytical Advances in the Ex Vivo Challenge Efficacy Assay.

The ex vivo challenge assay is being increasingly used as an efficacy endpoint during early human clinical trials of HIV prevention treatments. There is no standard methodology for the ex vivo challenge assay, although the use of different data collection methods and analytical parameters may impact results and reduce the comparability of findings between trials. In this analysis, we describe the impact of data imputation methods, kit type, testing schedule and tissue type on variability, statistical power, and ex vivo HIV growth kinetics. Data were p24 antigen (pg/ml) measurements collected from clinical trials of candidate microbicides where rectal (n = 502), cervical (n = 88), and vaginal (n = 110) tissues were challenged with HIV-1BaL ex vivo. Imputation of missing data using a nonlinear mixed effect model was found to provide an improved fit compared to imputation using half the limit of detection. The rectal virus growth period was found to be earlier and of a relatively shorter duration than the growth period for cervical and vaginal tissue types. On average, only four rectal tissue challenge assays in each treatment and control group would be needed to find a one log difference in p24 to be significant (alpha = 0.05), but a larger sample size was predicted to be needed for either cervical (n = 21) or vaginal (n = 10) tissue comparisons. Overall, the results indicated that improvements could be made in the design and analysis of the ex vivo challenge assay to provide a more standardized and powerful assay to compare efficacy of microbicide products.

Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infection of ectocervical tissues with HIV-1BaL among PRE women (n = 20) in the follicular and luteal phases of the menstrual cycle and POST women (n = 17) at baseline and after ∼1 month of treatment with 0.01% vaginal E2 cream. Compared to PRE women, we measured higher levels of p24 antigen after ex vivo infection in tissues from POST women. POST women had a significantly thinner vaginal epithelium with decreased tight junction proteins and a higher density of mucosal immune T cells and lower levels of CD1a antigen-presenting cells, antimicrobial peptides, and inflammatory cytokines in the CVL (p values <.05). POST women had higher vaginal pH and lower vaginal Lactobacilli (p values <.05) than PRE women. After vaginal E2 therapy, CV endpoints and ex vivo HIV replication in POST tissues were similar to those observed in PRE tissues. The CV mucosa in POST women is thinned and compromised, with increased HIV-target immune cells and decreased antimicrobial factors, being more susceptible to HIV infection. After POST women receive topical E2 treatment, mucosal endpoints are similar to PRE levels.