Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia-Results of a phase 1/2 randomized, double-blinded, controlled trial.

Background: A more affordable pneumococcal conjugate vaccine (PCV) that provides comparable protection to current PCVs is needed to ensure sustainable access in resource-limited settings. Serum Institute of India Pvt. Ltd.

The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition.

Reproductive age women may choose to concurrently use topical antiretrovirals and hormonal contraceptives (HCs) to simultaneously prevent HIV-1 infection and unintended/mistimed pregnancy. There are conflicting data on the effect of HCs on mucosal susceptibility to HIV-1. The objective of this study was to evaluate cervicovaginal (CV) mucosal data from healthy women before and after initiation of either oral contraceptive pills (OCPs) or depot medroxyprogesterone acetate (DMPA) injection.

Effect of Hormonal Contraception on Pharmacokinetics of Vaginal Tenofovir in Healthy Women: Increased Tenofovir Diphosphate in Injectable Depot Medroxyprogesterone Acetate Users.

Objective: Endogenous and exogenous contraceptive hormones may affect mucosal pharmacokinetics (PKs) of topical antiretrovirals such as tenofovir. We present PK data from healthy women using tenofovir vaginal gel, at baseline (follicular and luteal phases) and after oral contraceptive pill (OCP) or depot medroxyprogesterone acetate (DMPA) use.

Methods: CONRAD A10-114 was a prospective, interventional, open-label, parallel study.

Contraceptive efficacy, safety, fit, and acceptability of a single-size diaphragm developed with end-user input.

Objective: To estimate contraceptive efficacy, safety, acceptability, and fit of a single-size diaphragm used with contraceptive gel.

Methods: We conducted a multicenter trial in which 450 couples used the single-size diaphragm, 300 randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1, 3, and 6.

A randomized controlled trial of a brief intervention to reduce alcohol use among female sex workers in Mombasa, Kenya.

Objective: We assessed whether a brief alcohol intervention would lead to reduced alcohol use and sexually transmitted infection (STI)/HIV incidence and related sexual risk behaviors among moderate drinking female sex workers.

Methods: A randomized controlled intervention trial was conducted with 818 female sex workers affiliated with the AIDS, Population, Health, and Integrated Assistance II project in Mombasa, Kenya. Eligible women were hazardous or harmful drinkers who scored between 7 and 19 (full range, 1-40) on the Alcohol Use Disorders Identification Test.

Pharmacokinetics of subcutaneous depot medroxyprogesterone acetate injected in the upper arm.

Background: The abdomen and thigh are recommended injection sites in the label for Depo-SubQ Provera 104™. We evaluated the pharmacokinetic profile of medroxyprogesterone acetate (MPA) following injection of Depo-SubQ Provera 104 in the upper arm, a preferred injection site in developing countries.

Study Design: Twenty-six women in Norfolk, VA, received a single injection of Depo-SubQ Provera 104 in the upper arm in this prospective noncomparative study.

Toward early safety alert endpoints: exploring biomarkers suggestive of microbicide failure.

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days.

Colposcopy: still useful in microbicide safety trials?

Background: Colposcopy is used to evaluate vaginal microbicides, but its link to risk of HIV is unknown. This reanalysis of 9 safety studies determined the impact of omitting colposcopy on the number of findings detected and assessed whether colposcopy was useful in identifying nonoxynol-9 (N-9) as an unsafe product in one study.

Methods: Product-related findings seen with naked eye and colposcopy or by colposcopy alone were evaluated.

Baseline variation and associations between subject characteristics and five cytokine biomarkers of vaginal safety among healthy non-pregnant women in microbicide trials.

Interleukins (IL)-8, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) have emerged as indicators of vaginal inflammation and HIV-1 transmission risk. We provide values and factors of normal variation of these immune mediators in premenopausal women to allow their wider clinical application as biomarkers of vaginal health. Cross-sectional analyzes (Kruskal-Wallis and Wilcoxon exact tests) of cytokine concentrations in relation to sociodemographic variables and Nugent score were performed on baseline (prior to product) cervicovaginal lavage from two Phase I randomized microbicide trials.

Quinacrine sterilization and gynecologic cancers: a case-control study in northern Vietnam.

Background: Over 100,000 women worldwide have been sterilized by insertion of quinacrine into the uterus to induce tubal scarring. Concern has been expressed about possible carcinogenicity, and specifically the risk of uterine cancer.

Methods: From 2001 through 2006, we conducted a population-based, case-control study of gynecologic cancers in 12 provinces in northern Vietnam, where relatively large numbers of women had received quinacrine.

Comparative crossover study of the PATH Woman's Condom and the FC Female Condom.

Background: Only one female condom [FC1 Female Condom (FC1)] is currently marketed, but it is poorly utilized, perhaps due to difficulty with insertion, discomfort and suboptimal functional performance during intercourse. The Program for Appropriate Technology in Health (PATH) Woman's Condom (WC) was developed in an effort to overcome these obstacles.

Study Design: This was a randomized crossover study to evaluate the functional performance, safety and acceptability of the FC1 and WC.

Six-day randomized safety trial of intravaginal lime juice.

Objectives: Nigerian women reportedly apply lime juice intravaginally to protect themselves against HIV. In vitro data suggest that lime juice is virucidal, but only at cytotoxic concentrations. This is the first controlled, randomized safety trial of lime juice applied to the human vagina.

Safety of quinacrine contraceptive pellets: results from 10-year follow-up in Vietnam.

Background: This study was conducted to evaluate long-term safety of quinacrine pellets for nonsurgical sterilization among women in Vietnam.

Study Design: Observational cohort study of 2735 women who had quinacrine insertions between 1989 and 1993 compared to 1623 women who received an intrauterine device (IUD).

Results: Cumulative follow-up times for the quinacrine and IUD cohorts were 28,697 and 17,382 person-years, respectively, and losses to follow-up were 6% and 7%, respectively.

Contraceptive effectiveness of two insertions of quinacrine: results from 10-year follow-up in Vietnam.

Background: This study was conducted to evaluate the long-term effectiveness of two insertions of quinacrine pellets for nonsurgical sterilization among women in northern Vietnam.

Study Design: Observational cohort study of 1335 women who received two quinacrine insertions between 1989 and 1993.

Results: About 90% of the study population participated in the last round of interviews.

Phase I safety trial of two vaginal microbicide gels (Acidform or BufferGel) used with a diaphragm compared to KY jelly used with a diaphragm.

Objectives: To assess the safety and acceptability of 2 vaginal microbicide gels (Acidform and BufferGel) used with a diaphragm compared to KY Jelly used with a diaphragm among low-risk, sexually abstinent women.

Study Design: Eighty-one women enrolled in a randomized, masked, phase I safety study using a diaphragm with Acidform, BufferGel, or KY Jelly for 6 to 10 hours nightly for 14 nights. Physical examination, colposcopy, and lab studies were performed after 1 and 2 weeks of use.

Identifying appropriate IUD candidates in areas with high prevalence of sexually transmitted infections.

Background: The IUD is a highly effective, safe, inexpensive and long-lasting contraceptive. However, IUDs may increase PID risk during the early postinsertion period when inserted in women with cervical infections. We developed a simple algorithm to identify women at low risk of current sexually transmitted infection (STI) who are appropriate IUD candidates in regions with moderate or high STI prevalence.

Fourteen-day safety and acceptability study of the universal placebo gel.

Objective: This study evaluated the effect of the so-called universal placebo compared to the polystyrene sulfonate (PSS) placebo on genital irritation.

Design: A single-center, Phase I, randomized, closed-label study was performed to evaluate the genital irritation of microbicide placebo gels. Thirty healthy, sexually abstinent women were randomly assigned to apply 3.

Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study.

Background: Topical microbicides against the human immunodeficiency virus (HIV) 1 that are nonirritating to the female genital epithelium are urgently needed to slow the heterosexual spread of HIV infection. Products that are also effective contraceptives provide additional benefits. Cellulose sulfate (CS) is a noncytotoxic antifertility agent that exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV.

FemCap with removal strap: ease of removal, safety and acceptability.

Objectives: FemCap is a silicone-rubber barrier contraceptive approved for marketing in the United States. To address reported problems with removal and dislodgment, the device's developer added a strap to the device and increased the height of the brim. This trial assessed whether the new design reduced removal difficulties and had any effects on dislodgment, genital pain/discomfort, safety, and acceptability.

A randomized Phase I vaginal safety study of three concentrations of C31G vs. Extra Strength Gynol II.

Background: C31G is an antimicrobial and spermicidal agent that contains two surface-active compounds, cetyl betaine and myristamine oxide. It is being developed as a vaginal microbicide and contraceptive.

Method: Three C31G concentrations (0.

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study.

Objectives: To evaluate symptoms and signs of genital irritation, vaginal leakage and acceptability of polystyrene sulfonate (PSS), which is being studied as a vaginal contraceptive and microbicide.

Methods: Forty-nine women applied 2.5 mL of either 5% PSS, 10% PSS, PSS vehicle, or Conceptrol (a marketed spermicidal product containing 4% nonoxynol-9) for 6 consecutive days.

Diaphragms in clinical trials: is clinician fitting necessary?

Background: The need for fitting a contraceptive diaphragm has recently been questioned in the context of upcoming trials in which the ability of the diaphragm to prevent sexually transmitted infections will be tested. Being able to provide the same size device to all women would greatly simplify supplying the device and training the clinicians, provided that it does not compromise effectiveness.

Methods: Data from studies of Lea's Shield and FemCap, in which all women were sized for a standard diaphragm and half were randomized to use it during the studies, were reanalyzed to determine if it was feasible to give all women in a barrier study the same size diaphragm or, alternatively, to determine if diaphragm size could be predicted using an algorithm of one or more parameters.