Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco

Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13).Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures.ClinicalTrials.gov: NCT00131677

Complete Influenza Vaccination Trends for Children Six to Twenty-Three Months

OBJECTIVE: Prevention of influenza among infants and young children is a public health abstract priority because of their high risk for influenza-related complications. Depending on a child’s age and previous influenza vaccination history, they are recommended to receive either 1 dose or 2 doses of influenza vaccine to be considered fully vaccinated against influenza for the season. We compared estimates of full (complete) influenza vaccination coverage of children 6 to 23 months across 10 consecutive influenza seasons (2002–2012), by race/ethnicity, age group, and by number of doses required to be fully vaccinated given child’s vaccination history. METHODS: National Immunization Survey data were used to estimate full influenza vaccination status among children 6 to 23 months on the basis of provider report. Estimates were computed by using Kaplan-Meier survival analysis methods. RESULTS: Full influenza vaccination coverage among children 6 to 23 months increased from 4.8% in the 2002–2003 influenza season to 44.7% in the 2011–2012 season. In all 10 influenza seasons studied, non-Hispanic black children and Hispanic children had lower full influenza vaccination coverage than non-Hispanic white children. For all 10 influenza seasons, full influenza vaccination coverage was higher among children requiring only 1 dose compared with those requiring 2 doses. CONCLUSIONS: Less than half of children 6 to 23 months in the United States, and an even a smaller percentage of Hispanic and non-Hispanic black children, are fully vaccinated against influenza. More implementation of evidence-based strategies that increase the percentage of children who are fully vaccinated is needed

Assessment of a Microbicide Candidate among a Diverse Cohort of Urban Southern US Women and their Male Sexual Partners

Background: This mixed methods study reports on product acceptance from a Phase I clinical trial of a candidate non-nucleoside reverse transcriptase inhibitor (NNRTI) vaginal microbicide product (UC781). The product was evaluated in the context of a Phase I clinical trial in an area characterized by high HIV prevalence among minority women. The findings will inform the development of an acceptable microbicide that will address the needs of diverse women and their partners. Methods: This is a mixed methods study of 34 racially and ethnically diverse female participants and 10 male partners in Atlanta, Georgia. Chi-square tests for marginal homogeneity and kappa statistics were calculated to analyze differences between groups on product attributes and use intention. ANOVA was used to examine difference between the treatment groups. Qualitative data were analyzed via constant comparative methodology. Results: Thirty-four out of the original female cohort of 36 completed the questionnaire. ... See full text for complete abstract

Preclinical Testing of Candidate Topical Microbicides for Anti-Human Immunodeficiency Virus Type 1 Activity and Tissue Toxicity in a Human Cervical Explant Culture

A human cervical explant culture was utilized for the preclinical assessment of anti-human immunodeficiency virus type 1 (HIV-1) activity and tissue toxicity of formulated, candidate topical microbicides. Products tested included cellulose acetate 1,2-benzene dicarboxylate (CAP), a carrageenan-based product (PC-515), a naphthalene sulfonate polymer (PRO 2000), a lysine dendrimer (SPL7013), a nonnucleoside reverse transcriptase inhibitor (UC781), and an antimicrobial peptide (D2A21), along with their placebos. Cervical explants were cultured overnight with HIV-1 with or without product, washed, and monitored for signs of HIV-1 infection. HIV-1 infection was determined by p24gag levels in the basolateral medium and by immunohistochemical analysis of the explant. Product toxicity was measured by the MTT [1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan] assay and histology. CAP, PRO 2000, SPL7013, and UC781 consistently prevented HIV-1 infection in all explants tested. PC-515 and D2A21 prevented HIV-1 infection in 50% or fewer of the explants tested. Placebos did not prevent infection in any of the explants tested. With the exception of PRO 2000 (4%), the MTT assay and histological analysis of the other products and placebos showed minimal toxicity to the epithelium and submucosa. Collectively, these data suggest that this culture system can be used for evaluating the safety and efficacy of topical microbicides designed for vaginal use

Influenza vaccines licensed in the United States in healthy children: a systematic review and network meta-analysis (Protocol)

Abstract Background Influenza is an acute respiratory illness caused by influenza viruses, which occurs in epidemics worldwide every year. Children are an important target for prevention methods, including vaccination. While evidence about the decision on whether to vaccinate healthy children is robust, evidence supporting the decision of which of available vaccines to use remains unclear. This review will summarize the evidence about the efficacy and safety of the available vaccines for seasonal influenza licensed in the United States for use in healthy children. Methods/design An umbrella systematic review (SR) and network meta-analysis will be conducted of randomized controlled trials (RCTs). We will search for SRs to identify parallel RCTs evaluating inactive and/or live attenuated influenza vaccines licensed in the United States for use in healthy children to prevent influenza. Subsequently, we will update the literature search of the selected SRs to the present time to capture recent controlled studies. To complement the work focused on harms, we will also select observational studies focusing on post marketing retrospective studies. Inclusion will not be limited by language, publication date or publication status. To identify additional candidate studies, we will review the reference lists of the eligible primary studies and narrative reviews; we will query the expert members of the Advisory Committee on Immunization Practices and review references from their previous statement. Additionally, we will review the reports from the Institute of Medicine on the adverse effects of vaccines. Two reviewers will independently determine study eligibility and will extract descriptive, methodological (using the Cochrane risk of bias tool for RCTs and the Newcastle–Ottawa scale for observational studies) and efficacy data. When possible, we will conduct meta-analyses and network meta-analyses by combining indirect and direct comparisons. We will evaluate heterogeneity using the I2 statistic and the agreement of indirect comparisons and direct evidence. We will report the Cochrane Q test to determine the statistical significance of heterogeneity. The overall quality of evidence will be assessed following the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach. Discussion Our systematic review will allow patients, clinicians, guideline developers and policy makers to make evidence-based choices between the two available vaccine options, by providing information regarding benefits and harms of these types of vaccines.</p