Alexandra M. Minnis

Biomarker Validation of Reports of Recent Sexual Activity: Results of a Randomized Controlled Study in Zimbabwe

Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fishers exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir’s antiviral effect substantially influence PrEP efficacy. Trial Registration ClinicalTrials.gov NCT00592124

Determinants of contraceptive method among young women at risk for unintended pregnancy and sexually transmitted infections

The objective of this study was to examine the relationship between contraceptive method choice, sexual risk and various demographic and social factors. Data were collected on 378, 15- to 24-year-old women, recruited from health clinics and through community outreach in Northern California. Logistic regression analysis was used to estimate the association of predictors with contraceptive method used at last sex. Asian and Latina women were less likely to use any method. Women who were raised with a religion, or thought they were infertile, were also less likely to use any method. Women with multiple partners were generally less likely to use any method, but were more likely to use barrier methods when they did use one. Few women (7%) were dual method users. Women appear to act in a rational fashion within their own social context and may use no methods at all or use methods that are less effective for pregnancy prevention but offer more protection from sexually transmitted infections.

Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions

Objectives: To evaluate evidence for the effectiveness of female controlled physical and chemical barrier methods in preventing STI/HIV transmission, to examine recent reviews on microbicide development, and to highlight promising research directions. To discuss challenges in conducting effectiveness research and in translating results to public health intervention. Methods: Systematic review of articles that examined the disease prevention effectiveness of at least one female controlled barrier method. Review of conference abstracts that presented clinical and preclinical microbicide data. Results: Randomised controlled trials provide evidence that female condoms confer as much protection from STIs as male condoms. Observational studies suggest that the diaphragm protects against STI pathogens. Several microbicide effectiveness studies are under way and new directions, such as adaptation of therapeutic agents as preventive products, are being examined. Substantial attention is now given to product formulation and novel delivery strategies. Combining microbicide products with different mechanisms of action as well as combining chemical and physical barriers will be necessary to maximise prevention effectiveness. Conclusions: Increased investment in the development and identification of female controlled barrier methods offers promise that additional products will be available in the years ahead. Generalising trial results to a community setting, promoting products that may be less effective than male condoms, and bringing an effective product to scale introduce public health challenges that warrant attention. The need for female controlled barrier methods that provide women with the opportunity to take an active role in reducing their STI/HIV risk are urgently needed and constitute an essential tool to prevent continued spread of these infections.

Reproductive health differences among Latin American- and US-born young women.

Investigations of reproductive health within Lationos living in the United States suggest that sexual behaviors and contraception use practices vary by ethnicity and between foreign- and US-born adolescents. This article compares high-risk sexual behaviors and reproductive health among foreign-born Latinas, US-born Latinas, and US-born non-Latinas aged 15–24 years. We recruited 361 females from reproductive health clinics in the San Francisco Bay Area of California between 1995 and 1998; these women completed an interview that assessed sexual risk behaviors and history of pregnancy, abortion, and sexually transmitted infections. Current chlamydial and gonococcal infections were detected through biological testing. Among participants aged 15–18 years, US-born Latinas were more likely to have been pregnant (odds ratio [OR] comparing US-born Latinas and US-born non-Latinas=3.9, 95% confidence interval [CI] 1.3, 11.4), whereas among respondents aged 19–24 years, foreign-born Latinas were more likely to have been pregnant than US-born Latinas (OR=11.3, 95% CI 1.0, 130.8) and US-born non-Latinas (OR=64.2, 95%CI 9.9, 416.3). US-born Latinas were most likely to have had an abortion (OR comparing US-born Latinas and US-born non-Latinas=2.0, 95% CI 0.9, 4.7). They were also most likely to have chlamydial infection at study enrollment (8.2% prevalence compared to 2.2% and 1.0% for foreign-born Latinas and US-born non-Latinas, respectively; P=0.009). Reproductive health differences between foreign and US-born females and within the US-born population warrant further examination and highlight the need for targeted prevention.

Pregnancy intentions and teenage pregnancy among Latinas: a mediation analysis.

CONTEXT The extent to which pregnancy intentions mediate the relationship between individual, familial and cultural characteristics and adolescent pregnancy is not well understood. The role of intentions may be particularly important among Latina teenagers, whose attitudes toward pregnancy are more favorable than those of other groups and whose pregnancy rates are high. METHODS Prospective, time-varying data from 2001-2004 were used to investigate whether two measures of pregnancy intentions, wantedness and happiness, mediated associations between risk factors and pregnancy among 213 Latina adolescents in San Francisco. Participants were tested for pregnancy and interviewed about pregnancy intentions, partnerships, family characteristics and activities every six months for two years. Associations and mediation were examined using logistic regression. RESULTS Neither pregnancy intention variable mediated relationships between participant characteristics and pregnancy. After adjustment for other measures, wantedness was strongly associated with pregnancy (odds ratio, 2.6), while happiness was not. Having a strong family orientation was associated with happiness (3.7) but unrelated to pregnancy. Low power in a sexual relationship with a main partner was associated with an elevated risk of pregnancy (3.3). If the pregnancy intentions of all participants were changed to definitely not wanting pregnancy, the estimated decline in pregnancy risk would be 16%. CONCLUSIONS Pregnancy intentions were important not as mediators but rather as independent risk factors for pregnancy. Differences in pregnancy rates between groups of Latinas may be less a function of intentional choice than of situational factors. Interventions and research should focus on identifying and targeting factors that hinder effective contraceptive use among teenagers who want to avoid pregnancy.

Barrier contraceptive method acceptability and choice are not reliable indicators of use

Background The need for safe and effective female-controlled methods that protect against sexually transmitted pathogens is widely recognized. Product effectiveness is inextricably bound to use, and, therefore, the needs and preferences of potential consumers must be considered. The degree to which measures of acceptability correlate with actual barrier method use remains unexamined. Goal The goal was to evaluate associations between measures of acceptability and use of existing over-the-counter barrier methods. Study Design In the San Francisco Bay Area, 510 females aged 15 to 30 years were recruited from reproductive health clinics for this longitudinal study. Results Neither hypothetical acceptability nor product choice predicted use. Fewer than 50% of participants who chose a female-controlled method used it. Similarly, method satisfaction was not associated with use (14.3–51.4% of satisfied users used the method again). However, dissatisfaction was predictive of low levels of subsequent use (0–15.3% used the method again). Male condoms were used despite dissatisfaction. Conclusion The lack of association among assessments of acceptability, choice, satisfaction, and use suggests a need to reframe how product acceptability is evaluated in prevention research so it is more predictive of method use.

Concurrent partnerships among adolescents in a Latino community: the Mission District of San Francisco, California.

Objectives: Latino adolescents in the United States are disproportionately affected by sexually transmitted infections, yet knowledge of their sexual networks, particularly concurrent sex partners, is limited. Goal: The goal of this study was to describe the prevalence, patterns, and correlates of sexual concurrency among adolescents in an urban neighborhood. Study Design: The authors conducted cross-sectional analyses of 368 sexually active youth recruited from public venues within a predominantly Latino neighborhood in San Francisco, California. Results: During the prior 6 months, 20% of sexually experienced youth had concurrent partnerships, but this was more likely among males (27%) as females (12%) (odds ratio = 2.6; 95% confidence interval = 1.5–4.5). Sexually transmitted infection prevalence was too low to examine its association with concurrency. Factors that increased the likelihood of concurrency among males included: immigrant generation and being below grade level; and among females: older age and use of illegal substances. Conclusions: Ample opportunities to transmit sexually transmitted infections through concurrency were present, yet very few adolescents were infected, perhaps owing to adequate condom use within a neighborhood with low sexually transmitted infection prevalence.

Qualitative assessment of venues for purposive sampling of hard-to-reach youth. An illustration in a Latino community.

Background Latino youth suffer disproportionately from unintended pregnancy and sexually transmitted infections (STIs), but studies of the social context of their sexual behaviors are lacking. Goal Our qualitative assessment of recruitment venues in a Latino neighborhood had 3 objectives: to identify venues where youth at risk of unintended pregnancy and STIs could be found; to describe different youth “crowds”; and to investigate how and where youth meet their sex partners. Study Design We conducted ethnographic interviews with 62 youth recruited primarily from street sites. Mapping of venues was conducted with Map-Info. Results Youth crowds included the Regulars, gang-related crowds, street-economy affiliated crowds, and female crowds. Maps demonstrated the dominance of the venues in the Mission by gang members. Street sites are important venues for meeting sexual partners. Conclusion The qualitative assessment produced insights and hypotheses that can contribute to the planning of research, outreach, testing, and interventions with Latino youth.

ACASI and Face-to-Face Interviews Yield Inconsistent Estimates of Domestic Violence Among Women in India: The Samata Health Study 2005-2009

Background. Audio computer-assisted self-interviews (ACASI) are increasingly used in health research to improve the accuracy of data on sensitive behaviors. However, evidence is limited on its use among low-income populations in countries like India and for measurement of sensitive issues such as domestic violence. Method. We compared reports of domestic violence and three less sensitive behaviors related to household decision making and spousal communication in ACASI and face-to-face interviews (FTFI) among 464 young married women enrolled in a longitudinal study of gender-based power and adverse health outcomes in low-income communities in Bangalore, India. We used a test-retest design. At the 12-month study visit, we elicited responses from each participant through FTFI first, followed by ACASI. At the 24-month visit, we reversed the order, implementing ACASI first, followed by FTFI. Univariable log-linear regression models and kappa statistics were used to examine ACASI’s effects on self-reports. Results. Regression results showed significantly lower reporting in ACASI relative to FTFI at both visits, including for domestic violence (12-month risk ratio [RR] = 0.61, 95% CI = 0.52, 0.73; 24-month RR = 0.74, 95% CI = 0.62, 0.89). Response agreement between interview modes, calculated by kappa scores, was universally low, though highest for domestic violence (12-month κ = 0.45; 24-month κ = 0.48). Older age and greater educational attainment appeared associated with higher response agreement. Conclusions. Greater reporting in FTFI may be due to social desirability bias for the less sensitive questions and perceptions of therapeutic benefit for domestic violence. These results cast doubt on the appropriateness of using ACASI for measurement of sensitive behaviors in India.