Acceptability of and Adherence to an Antiretroviral-Based Vaginal Microbicide among Pregnant Women in the United States.

The MTN-008 trial was the first multi-dose study conducted to evaluate the safety of a microbicide gel (2:1 randomized to tenofovir 1% or hydroxycellulose (HEC) placebo gel) during pregnancy. The study aim was to evaluate safety, tolerability and pharmacokinetics of the study products. Procedures included daily gel administration, with Day 0 and Day 6 in clinic, and Days 1-5 at home. Because pregnancy may pose unique challenges to consistent gel use and acceptability, evaluation of adherence and acceptability was a secondary objective of the trial. The study enrolled healthy, HIV-negative, pregnant women aged 18-40 in Pittsburgh, PA and Birmingham, AL, USA in 2 consecutive groups: cohort 1 was 37-39 weeks gestation, cohort 2 was 34-36 weeks. Ninety-one women completed the study (45 and 46 in each cohort, respectively) and were evaluable per protocol. Adherence was evaluated using self-reports: participants completed a web-based computer-assisted self-interview (CASI) at Days 0 and 6 about gel attitudes and behaviors. At Day 6 trained research staff conducted a short interviewer-administered questionnaire with both structured and open-ended questions. Frequencies of quantitative data were tabulated in SAS and descriptive statistics are presented; open-ended textual data were summarized by a behavioral scientist experienced in qualitative analysis. Participants reported generally neutral perceptions of gel characteristics. A small number of women (7-8%) reported pain (6/90), other physical discomfort (7/90), or mental discomfort (7/90) associated with the process of applicator insertion. About 5% reported the same for the gel itself. Two-thirds (61/90) thought the gel was runny, many complained of bothersome gel leakage and several cited this reason for not inserting a full dose. The majority were not worried the gel would cause problems for their pregnancy or babies. Ninety-seven percent (83/86) said they would use the gel in the future if they were pregnant, and 90% (81/90) when nonpregnant. Self-reported adherence was high with 88% (79/90) reporting daily gel use on both the computerized and interviewer-administered questionnaires. The majority (67/90) reported no difficulty with daily use. However, drug was undetectable (<0.31 ng/mL) among 45% (27/60; 95% CI 32-58%) of the women on active product prior to observed dosing at Day 6. The most common reason for reported nonuse (N = 6) was forgetting. Study gel was generally acceptable, but many complained of a runny consistency (61/90) and leakage (83/90). No frequent or strong concerns about the effects of the study gel on the pregnancy/fetus were reported. Self-reported adherence to study gel self-administered at home for 5 days was high, however plasma drug levels suggest actual use may have been considerably lower. Findings from this study can provide insights relevant to use of other antiretroviral-based, vaginally-inserted HIV prevention methods during pregnancy.

Implementing Social Determinant of Health Screening in a Family Medicine Clinic: A Pilot Study.

While unmet social needs can perpetuate barriers to health equity, health care staff may feel unprepared to address these needs. This article describes a pilot study on implementing a screening process for social determinants of health in a family medicine clinic where there was no prior standard of care. A quality improvement approach was used to frame the implementation and evolution of screening and follow-up strategies for social needs. Social determinant of health screening was successfully implemented during this pilot of 400 encounters, revealing a 26.3% prevalence. Options for addressing social needs grew during the study, although no statistically significant impact was observed on measured short-term health outcomes. Physicians can use quality improvement to counter clinical inertia toward addressing social determinants of health and also to concurrently screen and develop appropriate patient-oriented solutions in their clinics.

A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy.

INTRODUCTION: Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy. METHODS: Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels. RESULTS: Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (p=0.18); therefore, their data were combined. Primary safety end point rates were similar for mothers randomized to the TFV gel vs placebo arm (72.7 and 68.8%, p=0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%, p=0.66). All women randomized to TFV had quantifiable serum levels within eight hours of dosing, with low overall median (interquartile range) day 0 and day 6 peak values (3.8 (2.0 to 7.0) and 5.8 (2.6 to 9.4) ng/mL, respectively). CONCLUSIONS: Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels.

Which spinal levels are identified by palpation of the iliac crests and the posterior superior iliac spines?

The line joining the superior aspect of the iliac crests posteriorly (the intercristal line) is commonly stated to cross the midline at the L4 or L4-5 spinal level on imaging. This study aimed to assess the spinal level identified through palpation of surface anatomy (iliac crests and posterior superior iliac spines) in adults and the level of agreement compared with the intercristal line identified through imaging. The study participants included consecutive adult patients undergoing prone fluoroscopically guided spinal injections for chronic low back pain at the Royal Orthopaedic Hospital, Birmingham, between April and July 2004. Prior to fluoroscopic imaging, each patient's surface anatomy was palpated by two examiners and lines created to form the palpated intercristal line and the posterior superior iliac spine line. Following imaging, the mid-line spinal levels identified by these palpated lines were recorded and the level of agreement (kappa coefficient) with the intercristal line formed by imaging of the iliac crests was assessed. The results showed that although the L4 or L4-5 spinal levels were identified on imaging of the intercristal line in 86.7% of 75 patients (49 female), the intercristal line formed through palpation tended to identify higher levels; the L3 or L3-4 spinal levels in 77.3% of cases and more commonly in females than in males (85.7 vs. 61.5%) and in patients with higher body mass indices. The level of agreement between the two lines was poor (kappa = 0.05). The posterior superior iliac spine line identified the S2 spinous process in 51% and the S1 in 44% of 60 (45 female) patients. The results suggest that formation of the intercristal line by palpation of the iliac crests identifies different spinal levels to those identified by imaging and that both methods should be regarded as different instruments. In the clinical situation, it may be more appropriate to consider that palpation of the intercristal line is a guide for identifying the L3 or L3-4 spinal levels rather than the L4 or L4-5 levels, particularly in females and patients with higher body mass indices.