Risk factors for incidence of sexually transmitted infections among women in a human immunodeficiency virus chemoprevention trial : VOICE (MTN-003).

CAPRISA, 2017.Abstract available in pdf

Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15–44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population

Tenofovir-based preexposure prophylaxis for HIV infection among African women.

CAPRISA, 2015.Abstract available in pdf

Human Antibody Responses to a Chlamydia-Secreted Protease Factor

We have previously identified a chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia-infected cells. Although CPAF is known to degrade host transcription factors required for major histocompatibility complex antigen expression in cultured cells, it is not clear whether CPAF is produced and maintains similar functions in humans infected with chlamydial organisms. We now report that CPAF does not preexist in chlamydial organisms and that CPAF synthesis requires live organism replication in cultured cells. Mice inoculated with live, but not mice inoculated with dead, chlamydial organisms produced a strong antibody response to CPAF, correlating CPAF-specific antibody production with CPAF synthesis in animals. Sera from women diagnosed with Chlamydia trachomatis cervicitis displayed higher levels of antibodies to CPAF than to either chlamydial major outer membrane protein or heat shock protein 60, suggesting that CPAF is both produced and immunogenic during human chlamydial infection

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

Diagnostic Assessment of Mycoplasma genitalium in Culture-Positive Women

Detection of Mycoplasma genitalium-mediated, chlamydia-negative nongonococcal urethritis and other M. genitalium-linked infectious etiologies has been very challenging. Although M. genitalium is considered a leading cause of genitourinary symptoms in men and women, extreme difficulties in its cultivation due to its highly fastidious nature and the lack of routine and effective diagnostic tests have slowed the generation of clinical data which directly implicate the presence of M. genitalium in disease pathogenesis. In this study, we compared enzyme-linked immunosorbent assays (ELISAs) and immunoblot and PCR assays in M. genitalium culture-positive women over 1 to 3 years of clinical visits to determine the usefulness of independent diagnostic strategies. Furthermore, the value of combinatorial diagnostic assessments is described, which provides insights into the dynamics of M. genitalium-host interactions. Overall, we show that neither ELISA nor PCR, alone or in combination, provides the sensitivity required to confidently predict the existence of viable M. genitalium organisms in cervical and vaginal samples. Additionally, culture-positive women exhibited a range of antibody responsiveness to M. genitalium based upon ELISA and immunoblot assessments, indicating immune diversity among this high-risk population

The Influence of Depression on Sexual Risk Reduction and STD Infection in a Controlled, Randomized Intervention Trial

BACKGROUND: A randomized controlled trial of SAFE, a cognitive/behavioral intervention, revealed that it significantly reduces reinfection and behavioral risks among participants compared with controls. However, studies suggest that depression may moderate intervention efficacy among affected persons because of impaired information processing, failure to recognize risk, or inability to change behavior. GOAL: We evaluated SAFE efficacy among depressed and nondepressed Mexican- and African American women after comparing initial risk factors by depression status. We further explored intervention effects in moderately and severely depressed women. STUDY DESIGN: We stratified 477 participants (249 intervention, 228 controls) according to their depression status at baseline determined by CES-D scores. Using chi and multivariate logistic regression, we evaluated differences in reinfection and behavioral risk at 6-month, 12-month, and 1-year cumulative follow-ups between groups within baseline depression strata. RESULTS: : At baseline, 74.4% of women were depressed and had significantly greater levels of behavioral risks than nondepressed women. At follow-up intervals, behavioral risks and reinfection rates were lower among intervention women compared with controls regardless of depression status. For example, at 1-year follow-up reinfection rates were 15.2% in nondepressed intervention women versus 21.4% in nondepressed controls (AOR = 0.6), and 18.6% in depressed intervention women versus 27.3% in depressed controls (AOR = 0.6). Moreover, reinfection was consistently lower among moderately and severely depressed intervention women than controls (moderately depressed: 19.3% vs. 27.2%, AOR = 0.6; severely depressed: 17.9% vs. 27.5%, AOR = 0.6). CONCLUSIONS: Despite significantly greater behavioral risk among depressed women at baseline, SAFE was equally successful in reducing reinfection and high-risk behavior among depressed and nondepressed participants

Reporting of adherence in the VOICE trial: Did disclosure of product nonuse increase at the termination visit?

VOICE—a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe—found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥ 90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report