Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop proceedings,National Institute of Allergy and Infectious Diseases,Bethesda, Maryland,USA, May 21, 2015

On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities. Meeting participants presented the results and experience of representative clinical trials of NA vaccines using a variety of alternative delivery devices, as well as a broader group of methods studied in animal models and at bench top, to improve upon the performance and/or avoid the drawbacks of conventional needle-syringe (N–S) delivery. The subjects described and discussed included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and lower respiratory, and intramuscular tissues; (2) devices and techniques for jet injection, solid, hollow, and dissolving microneedles, patches for topical passive diffusion or iontophoresis, electroporation, thermal microporation, nasal sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA, synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and microparticle vectors; and (4) the clinical experience and humoral, cellular, and cytokine immune responses observed for many of these target tissues, technologies, constructs, and carriers. This report summarizes the presentations and discussions from the workshop (https://web.archive.org/web/20160228112310/https://www.blsmeetings.net/NucleicAcidDeliveryDevices/), which was webcast live in its entirety and archived online (http://videocast.nih.gov/summary.asp?live=16059).     

Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-Valent vaccine,gender-neutral and multiple age cohort vaccination

BackgroundThe success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.MethodsSearches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.ResultsThirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9–14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.ConclusionsThese findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys’ vaccination or extending the age of vaccination.     

Facilitators of and barriers to HPV vaccination among sexual and gender minority patients at a Boston community health center

BackgroundYoung sexual minority individuals have lower human papillomavirus (HPV) vaccine completion rates than the general population, and little is known about how gender minority people perceive HPV vaccination. The aim of this study was to qualitatively identify patient-, provider-, and systems-level barriers and facilitators for HPV vaccination among sexual and gender minority (SGM) people.MethodsFifteen SGM-identified individuals, ages 23–26, were recruited at an urban community health center in Boston, MA, that specializes in care for SGM. Participants were enrolled in a study that utilized surveys and in-person focus groups. During focus groups, participants were asked to describe their perceived barriers and facilitators for completion of HPV vaccination.ResultsFourteen participants reported having a sexual minority identity, and five participants reported having a gender minority identity. Participants described the following factors influencing HPV vaccination: (1) at the patient level, low HPV-related knowledge and lack of engagement in care were associated with less vaccination, whereas fear of HPV-related disease motivated vaccination; (2) at the provider level, knowledge and SGM cultural-competence related to HPV was associated with patient willingness to be vaccinated; (3) at the systems level, SGM identity-affirming healthcare settings were associated with increased vaccination, whereas historical trends in HPV vaccine marketing selectively for cisgender women and lack of public awareness of HPV-related disease among SGM were associated with decreased vaccincation.ConclusionOur study identified internal and external barriers for HPV vaccination related among SGM patients. These findings highlight the need to increase public awareness about the risks of HPV-related disease among SGM and educate SGM youth about HPV-related disease and vaccine importance. Finally, this study supports the need for future interventions to cultivate SGM-competent providers and SGM identity-affirming healthcare settings as a way to increase HPV vaccination.     

Measuring vaccine acceptance among Canadian parents: A survey of the Canadian Immunization Research Network

Parental decision making about childhood vaccinations is complex and multidimensional. There is a perception that the number of parents having concerns regarding childhood vaccinations has been increasing in Canada. The aim of this study was to explore vaccine hesitancy among Canadian parents and to examine factors associated with a parent’s intention to vaccinate his/her child. Informed by the Theory of Planned Behaviour (TPB) this study assesses potential associations between parents’ knowledge, attitudes and beliefs toward vaccination and their intention to vaccinate their child in the future. A national sample of Canadian parents of children aged 24–59 months (N = 2013) was surveyed using an online survey methodology. Half of the surveyed parents strongly intended to have their child vaccinated in the future. Parents’ information needs and searches as well as parents’ trust in different institutions were associated with intention to vaccinate. Parents who reported having frequently looked for vaccine information, who considered that it was their role as parents to question vaccines, or who had previously experienced difficulty accessing vaccination services were less likely to strongly intend to vaccinate their child in the future. Parents who had a high level of trust in doctors and public health were most likely to strongly intend to vaccinate their child. Results of the multivariate analysis showed that positive attitudes (aOR = 8.0; 95% CI: 6.0, 10.4), higher perceived social support (aOR = 3.0; 95% CI: 2.3, 3.93), and higher perceived behavioural control (aOR = 1.8; 95% CI: 1.4, 2.43) were associated with parents’ intention to vaccinate their child. Findings of this study suggest that trust-building interventions that promote pro-vaccine social norms and that address negative attitudes toward vaccination could enhance vaccine acceptance among Canadian parents.     

Associations of Smoking,Physical Inactivity,Heavy Drinking,and Obesity with Quality-Adjusted Life Expectancy among US Adults with Depression

Objectives

To examine associations between four health behaviors (smoking, physical inactivity, heavy alcohol drinking, and obesity) and three health indices (health-related quality of life, life expectancy, and quality-adjusted life expectancy (QALE)) among US adults with depression.

Estimating the Cost to U.S. Health Departments to Conduct HIV Surveillance

Objectives

HIV case surveillance is a primary source of information for monitoring HIV burden in the United States and guiding the allocation of prevention and treatment funds. While the number of people living with HIV and the need for surveillance data have increased, little is known about the cost of surveillance. We estimated the economic cost to health departments of conducting high-quality HIV case surveillance.

Methods

We collected primary data on the unit cost and quantity of resources used to operate the HIV case surveillance program in Michigan, where HIV burden (i.e., the number of HIV cases) is moderate to high (n=14,864 cases). Based on Michigan''s data, we projected the expected annual HIV surveillance cost for U.S., state, local, and territorial health departments. We based our cost projection on the variation in the number of new and established cases, area-specific wages, and potential economies of scale.

Results

We estimated the annual total HIV surveillance cost to the Michigan health department to be $1,286,524 ($87/case), the annual total cost of new cases to be $108,657 ($133/case), and the annual total cost of established cases to be $1,177,867 ($84/case). Our projected median annual HIV surveillance cost per health department ranged from $210,600 in low-HIV burden sites to $1,835,000 in high-HIV burden sites.

Conclusions

Our analysis shows that a systematic approach to costing HIV surveillance at the health department level is feasible. For HIV surveillance, a substantial portion of total surveillance costs is attributable to maintaining established cases.An estimated 1.2 million people aged 13 years and older are living with human immunodeficiency virus (HIV) in the United States, and about 47,500 people are infected with the virus each year.^1,2 A recent HIV surveillance report shows that the number of people living with HIV increased by 8% from 2006 through 2009.³ The U.S. Centers for Disease Control and Prevention (CDC) has developed an HIV surveillance system for collecting, analyzing, and disseminating accurate information on the number of people with new HIV diagnoses (new cases) and those living with HIV infection (established cases).^4,5 Access to timely and high-quality surveillance data is essential to detect trends in the HIV burden and develop appropriate prevention and control measures.^4,6,7 The U.S. Department of Health and Human Services has closely aligned the $16 billion it spent in 2010 on HIV care, treatment, and prevention with the number of reported HIV cases in each state.⁸ HIV case surveillance additionally guides the implementation of test-and-treat prevention strategies that require data on timing of diagnosis, entry into and retention in care, and viral load (VL) suppression.^8–10 The Institute of Medicine recently identified HIV case surveillance as one of the data collection systems that could be used to monitor progress in achieving National HIV/AIDS Strategy goals.^11,12The purpose of this analysis was to estimate the economic cost to health departments to conduct high-quality HIV case surveillance, where high quality is defined as meeting or exceeding CDC data quality standards regarding the completeness and timeliness of reporting diagnosed HIV cases and ascertaining duplicate cases and deaths.^6,7 We examined potential variation in costs across health departments based on differences in the number of new vs. established HIV cases, area-specific wages, and potential economies of scale. Results from the analysis could help inform surveillance funding allocation across health departments and enable health departments to more accurately assess their own costs attributable to new and established HIV cases.     

Education in Quality Improvement for Pediatric Practice: An Online Program to Teach Clinicians QI

BackgroundEducation in Quality Improvement for Pediatric Practice (EQIPP) is an online program designed to improve evidence-based care delivery by teaching front-line clinicians quality improvement (QI) skills. Our objective was to evaluate EQIPP data to characterize 1) participant enrollment, use patterns, and demographics; 2) changes in performance in clinical QI measures from baseline to follow-up measurement; and 3) participant experience.MethodsWe conducted an observational study of EQIPP participants utilizing 1 of 3 modules (asthma, immunizations, gastroesophageal reflux disease) from 2009 to 2013. Enrollment and use, demographic, and quality measure data were extracted directly from the EQIPP system; participant experience was assessed via an optional online survey.ResultsStudy participants (n = 3501) were diverse in their gender, age, and race; most were board certified. Significant quality gaps were observed across many of the quality measures at baseline; sizable improvements were observed across most quality measures at follow-up. Participants were generally satisfied with their experience. The most influential module elements were collecting and analyzing data, creating and implementing aim statements and improvement plans, and completing “QI Basics.”ConclusionsOnline educational programs, such as EQIPP, hold promise for front-line clinicians to learn QI. The sustainability of the observed improvements in care processes and their linkage to improvements in health outcomes are unknown and are an essential topic for future study.     

An alternative strategy to western blot as a confirmatory diagnostic test for HIV infection

BackgroundIn China, western blot (WB) is the recommended procedure for the diagnosis of HIV infection. However, this technique is time consuming and labor intensive, and its complexity restricts wide application in resource-limited regions.ObjectiveThe aim of this study was to evaluate the efficacy of a dry blood spots (DBS)–urine paired enzyme-linked immunosorbent assay (ELISA) test, instead of WB, for HIV antibody detection.Study designPlasma, DBS, and urine samples were collected from 1213 subjects from different populations. Two diagnostic testing strategies were conducted in parallel. The equivalence of the paired ELISA and WB strategies was assessed.ResultsA diagnosis of HIV was determined in 250 subjects according to the paired ELISA test, and in 249 according to the WB strategy. The discordant case was judged HIV-positive during follow-up. In total, 18 subjects were diagnosed with possible HIV using the paired ELISA test, among whom, 11 subjects tested negative with WB, and one was confirmed to be HIV-positive during follow-up. For the remaining 945 subjects, both strategies indicated a negative result. The kappa test indicated good conformity (kappa = 0.954) between the two diagnostic strategies.ConclusionThe DBS–urine paired ELISA could be applied as an alternative to WB in HIV diagnosis, which would be valuable in resource-limited regions owing to the associated affordability and ease of use.