Paula M. Frew

Microneedle patches: Usability and acceptability for self-vaccination against influenza

While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93-96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55-74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51-75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage.

Understanding Racial HIV/STI Disparities in Black and White Men Who Have Sex with Men: A Multilevel Approach

Background The reasons for black/white disparities in HIV epidemics among men who have sex with men have puzzled researchers for decades. Understanding reasons for these disparities requires looking beyond individual-level behavioral risk to a more comprehensive framework. Methods and Findings From July 2010-Decemeber 2012, 803 men (454 black, 349 white) were recruited through venue-based and online sampling; consenting men were provided HIV and STI testing, completed a behavioral survey and a sex partner inventory, and provided place of residence for geocoding. HIV prevalence was higher among black (43%) versus white (13% MSM (prevalence ratio (PR) 3.3, 95% confidence interval (CI): 2.5–4.4). Among HIV-positive men, the median CD4 count was significantly lower for black (490 cells/µL) than white (577 cells/µL) MSM; there was no difference in the HIV RNA viral load by race. Black men were younger, more likely to be bisexual and unemployed, had less educational attainment, and reported fewer male sex partners, fewer unprotected anal sex partners, and less non-injection drug use. Black MSM were significantly more likely than white MSM to have rectal chlamydia and gonorrhea, were more likely to have racially concordant partnerships, more likely to have casual (one-time) partners, and less likely to discuss serostatus with partners. The census tracts where black MSM lived had higher rates of poverty and unemployment, and lower median income. They also had lower proportions of male-male households, lower male to female sex ratios, and lower HIV diagnosis rates. Conclusions Among black and white MSM in Atlanta, disparities in HIV and STI prevalence by race are comparable to those observed nationally. We identified differences between black and white MSM at the individual, dyadic/sexual network, and community levels. The reasons for black/white disparities in HIV prevalence in Atlanta are complex, and will likely require a multilevel framework to understand comprehensively.

Racial and ethnic differences in knowledge and willingness to participate in HIV vaccine trials in an urban population in the Southeastern US

Racial/ethnic minorities in the Southeastern USA are disproportionately affected by HIV, and would benefit from a preventive vaccine. We conducted a cross-sectional survey of 220 community college students in Atlanta to evaluate racial/ethnic differences in knowledge and willingness to participate in HIV vaccine trials. Willingness to participate did not differ by race/ethnicity, age, or gender, and was not associated with knowledge. African-Americans and Asians were more likely than Whites to: believe that an HIV vaccine exists, but is being withheld from the public; believe that AIDS was caused by a government conspiracy; feel that having other participants and investigators of their ethnic background in the trial was important. Misconceptions regarding HIV vaccines are common and differ by race/ethnicity. However, willingness to participate was not associated with knowledge or race/ethnicity. Efforts to increase participation should address the ethnic diversity of the trial personnel, and education to eliminate misconceptions about HIV vaccines and trials.

The Comparability of Men Who Have Sex With Men Recruited From Venue-Time-Space Sampling and Facebook: A Cohort Study

Background Recruiting valid samples of men who have sex with men (MSM) is a key component of the US human immunodeficiency virus (HIV) surveillance and of research studies seeking to improve HIV prevention for MSM. Social media, such as Facebook, may present an opportunity to reach broad samples of MSM, but the extent to which those samples are comparable with men recruited from venue-based, time-space sampling (VBTS) is unknown. Objective The objective of this study was to assess the comparability of MSM recruited via VBTS and Facebook. Methods HIV-negative and HIV-positive black and white MSM were recruited from June 2010 to December 2012 using VBTS and Facebook in Atlanta, GA. We compared the self-reported venue attendance, demographic characteristics, sexual and risk behaviors, history of HIV-testing, and HIV and sexually transmitted infection (STI) prevalence between Facebook- and VTBS-recruited MSM overall and by race. Multivariate logistic and negative binomial models estimated age/race adjusted ratios. The Kaplan-Meier method was used to assess 24-month retention. Results We recruited 803 MSM, of whom 110 (34/110, 30.9% black MSM, 76/110, 69.1% white MSM) were recruited via Facebook and 693 (420/693, 60.6% black MSM, 273/693, 39.4% white MSM) were recruited through VTBS. Facebook recruits had high rates of venue attendance in the previous month (26/34, 77% among black and 71/76, 93% among white MSM; between-race P=.01). MSM recruited on Facebook were generally older, with significant age differences among black MSM (P=.02), but not white MSM (P=.14). In adjusted multivariate models, VBTS-recruited MSM had fewer total partners (risk ratio [RR]=0.78, 95% CI 0.64-0.95; P=.01) and unprotected anal intercourse (UAI) partners (RR=0.54, 95% CI 0.40-0.72; P<.001) in the previous 12 months. No significant differences were observed in HIV testing or HIV/STI prevalence. Retention to the 24-month visit varied from 81% for black and 70% for white MSM recruited via Facebook, to 77% for black and 78% for white MSM recruited at venues. There was no statistically significant differences in retention between the four groups (log-rank P=.64). Conclusions VBTS and Facebook recruitment methods yielded similar samples of MSM in terms of HIV-testing patterns, and prevalence of HIV/STI, with no differences in study retention. Most Facebook-recruited men also attended venues where VTBS recruitment was conducted. Surveillance and research studies may recruit via Facebook with little evidence of bias, relative to VBTS.

Measuring Population Transmission Risk for HIV: An Alternative Metric of Exposure Risk in Men Who Have Sex with Men (MSM) in the US

Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. MSM with plasma VL>400 copies/mL were defined as having ‘transmission risk’. We calculated HIV prevalence, CVL, PVL, percent of HIV-positive with undetectable viral loads, and prevalence of plasma VL>400 copies/ml (%VL400) for black and white MSM. We used Monte Carlo simulation incorporating data on sexual mixing by race to estimate exposure of black and white HIV-negative MSM to a partner with transmission risk via unprotected anal intercourse (UAI). Of 709 MSM recruited, 42% (168/399) black and 14% (44/310) white MSM tested HIV-positive (p<.0001). No significant differences were seen in CVL, PVL, or percent of HIV positive with undetectable viral loads. The %VL400 was 25% (98/393) for black vs. 8% (25/310) for white MSM (p<.0001). Black MSM with 2 UAI partners were estimated to have 40% probability (95% CI: 35%, 45%) of having ≥1 UAI partner with transmission risk vs. 20% for white MSM (CI: 15%, 24%). Discussion Despite similarities in other metrics, black MSM in our cohort are three times as likely as white MSM to have HIV transmission risk. With comparable risk behaviors, HIV-negative black MSM have a substantially higher likelihood of encountering a UAI partner at risk of transmitting HIV. Our results support increasing HIV testing, linkage to care, and antiretroviral treatment of HIV-positive MSM to reduce prevalence of those with transmission risk, particularly for black MSM.

The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial

BACKGROUND Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. METHODS The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat. Secondary immunogenicity outcomes are antibody titres at day 28 and percentages of seroconversion and seroprotection, all determined by haemagglutination inhibition antibody assay. The trial is completed and registered with ClinicalTrials.gov, number NCT02438423. FINDINGS Between June 23, 2015, and Sept 25, 2015, 100 participants were enrolled and randomly assigned to a group. There were no treatment-related serious adverse events, no treatment-related unsolicited grade 3 or higher adverse events, and no new-onset chronic illnesses. Among vaccinated groups (vaccine via health-care worker administered microneedle patch or intramuscular injection, or self-administered microneedle patch), overall incidence of solicited adverse events (n=89 vs n=73 vs n=73) and unsolicited adverse events (n=18 vs n=12 vs n=14) were similar. Reactogenicity was mild, transient, and most commonly reported as tenderness (15 [60%] of 25 participants [95% CI 39-79]) and pain (11 [44%] of 25 [24-65]) after intramuscular injection; and as tenderness (33 [66%] of 50 [51-79]), erythema (20 [40%] of 50 [26-55]), and pruritus (41 [82%] of 50 [69-91]) after vaccination by microneedle patch application. The geometric mean titres were similar at day 28 between the microneedle patch administered by a health-care worker versus the intramuscular route for the H1N1 strain (1197 [95% CI 855-1675] vs 997 [703-1415]; p=0·5), the H3N2 strain (287 [192-430] vs 223 [160-312]; p=0·4), and the B strain (126 [86-184] vs 94 [73-122]; p=0·06). Similar geometric mean titres were reported in participants who self-administered the microneedle patch (all p>0·05). The seroconversion percentages were significantly higher at day 28 after microneedle patch vaccination compared with placebo (all p<0·0001) and were similar to intramuscular injection (all p>0·01). INTERPRETATION Use of dissolvable microneedle patches for influenza vaccination was well tolerated and generated robust antibody responses. FUNDING National Institutes of Health.

Acceptance of a Vaccine Against Novel Influenza A (H1N1) Virus Among Health Care Workers in Two Major Cities in Mexico

BACKGROUND AND AIMS Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico. METHODS We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico-Mexico City and Guadalajara-between June and September 2009. RESULTS A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective. CONCLUSIONS Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus.

Factors Associated with Intention to Receive Influenza and Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccines during Pregnancy: A Focus on Vaccine Hesitancy and Perceptions of Disease Severity and Vaccine Safety.

BACKGROUND: Improving influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women is needed. PURPOSE: To assess factors associated with intention to receive influenza and/or Tdap vaccinations during pregnancy with a focus on perceptions of influenza and pertussis disease severity and influenza vaccine safety. METHODS: Participants were 325 pregnant women in Georgia recruited from December 2012 – April 2013 who had not yet received a 2012/2013 influenza vaccine or a Tdap vaccine while pregnant. Women completed a survey assessing influenza vaccination history, likelihood of receiving antenatal influenza and/or Tdap vaccines, and knowledge, attitudes and beliefs about influenza, pertussis, and their associated vaccines. RESULTS: Seventy-three percent and 81% of women believed influenza and pertussis, respectively, would be serious during pregnancy while 87% and 92% believed influenza and pertussis, respectively, would be serious to their infants. Perception of pertussis severity for their infant was strongly associated with an intention to receive a Tdap vaccine before delivery (p=0.004). Despite perceptions of disease severity for themselves and their infants, only 34% and 44% intended to receive antenatal influenza and Tdap vaccines, respectively. Forty-six percent had low perceptions of safety regarding the influenza vaccine during pregnancy, and compared to women who perceived the influenza vaccine as safe, women who perceived the vaccine as unsafe were less likely to intend to receive antenatal influenza (48% vs. 20%; p < 0.001) or Tdap (53% vs. 33%; p < 0.001) vaccinations. CONCLUSIONS: Results from this baseline survey suggest that while pregnant women who remain unvaccinated against influenza within the first three months of the putative influenza season may be aware of the risks influenza and pertussis pose to themselves and their infants, many remain reluctant to receive influenza and Tdap vaccines antenatally. To improve vaccine uptake in the obstetric setting, our findings support development of evidence-based vaccine promotion interventions which emphasize vaccine safety during pregnancy and mention disease severity in infancy.

Recruitment and Retention of Pregnant Women Into Clinical Research Trials: An Overview of Challenges, Facilitators, and Best Practices

Pregnant women are a vulnerable group who are needed in clinical research studies to advance prevention and treatment options for this population. Yet, pregnant women remain underrepresented in clinical research. Through the lens of the socioecological model, we highlight reported barriers and facilitators to recruitment and retention of pregnant women in studies that sought their participation. We trace historical, policy-based reasons for the exclusion of pregnant women in clinical studies to present-day rationale for inclusion of this group. The findings highlight why it has been difficult to recruit and retain this population over time. A body of literature suggests that integrative sampling and recruitment methods that leverage the influence and reach of prenatal providers will overcome recruitment challenges. We argue that these strategies, in combination with building strong engagement with existing community-based organizations, will enable teams to more effectively promote and retain pregnant women in future longitudinal cohort studies.

Lack of Awareness of Human Immunodeficiency Virus (HIV) Infection: Problems and Solutions With Self-reported HIV Serostatus of Men Who Have Sex With Men.

Using only self-reported information likely overestimates lack of awareness of HIV status for black MSM. Estimates that also incorporate laboratory and case surveillance measures do not show significant racial disparity in lack of awareness of HIV status.