Adolescent and adult participation in an HIV vaccine trial preparedness cohort in South Africa

PURPOSE: The importance of involving adolescents in HIV prevention trials has been recognized, but there have been few experiences reported from sub-Saharan Africa. We analyzed adult and adolescent data from a cohort study conducted to assess the feasibility of involving adolescents and adults in HIV vaccine-related studies. METHODS: Two hundred HIV-negative participants aged 16 to 40 years were enrolled, including 86 (43%) adolescents. At baseline, sexual risk behavior and willingness to participate (WTP) in future HIV vaccine trials questionnaires were administered. Three monthly HIV counseling, pregnancy, HIV and syphilis tests were performed. Risk questionnaires were repeated at 6 months and WTP at 12 months. RESULTS: No significant difference in retention between adults (83%) and adolescents (87%) was noted (p = .58). Initially, more adults (40%) reported WTP compared to adolescents (13%) (p < .001). At the end of the study both groups reported higher levels of WTP; increasing to 40% among adolescents. HIV incidence during the study was 9.2 infections per 100 person-years (95% confidence interval [CI]: 4.4-19.2) among adolescents compared to 5.8 (95% CI 2.6-12.9) in adults (p = .42). CONCLUSIONS: Retention of high-risk HIV-negative adolescents in a cohort study is feasible. Following education, adolescents reported improved WTP. The high HIV incidence rate in adolescents highlights the importance of including this group in prevention trials.     

Adolescent decision making about participation in a hypothetical HIV vaccine trial

PurposeThe purpose of this study was to examine the process of adolescent decision-making about participation in an HIV vaccine clinical trial, comparing it to adult models of informed consent with attention to developmental differences.MethodsAs part of a larger study of preventive misconception in adolescent HIV vaccine trials, we interviewed 33 male and female 16–19-year-olds who have sex with men. Participants underwent a simulated HIV vaccine trial consent process, and then completed a semistructured interview about their decision making process when deciding whether or not to enroll in and HIV vaccine trial. An ethnographic content analysis approach was utilized.ResultsTwelve concepts related to adolescents’ decision-making about participation in an HIV vaccine trial were identified and mapped onto Appelbaum and Grisso's four components of decision making capacity including understanding of vaccines and how they work, the purpose of the study, trial procedures, and perceived trial risks and benefits, an appreciation of their own situation, the discussion and weighing of risks and benefits, discussing the need to consult with others about participation, motivations for participation, and their choice to participate.ConclusionThe results of this study suggest that most adolescents at high risk for HIV demonstrate the key abilities needed to make meaningful decisions about HIV vaccine clinical trial participation.     

Selectively willing and conditionally able: HIV vaccine trial participation among women at "high risk" of HIV infection

Efficacy studies of investigational HIV vaccines require enrollment of individuals at ‘high risk’ for HIV. This paper examines participation in HIV vaccine trials among women at ‘high risk’ for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, care-giving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at ‘high risk’ can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals’ thinking about research participation.     

HIV vaccine trial in Kenya

This article presents a trial study of an HIV vaccine in Kenya. A joint Kenyan-Canadian-British HIV vaccine trial was launched in March of 1999. It is supported by the US-based International AIDS Vaccine Initiative (IAVI). STD clinics will be used as the basis of trials, and volunteers will be injected with genetic material developed from local HIV strains (most vaccine research up to this point has involved strains found in Europe or North America). Concerns have been raised that the vaccine could actually cause AIDS. Professor Ndinya Achola of the University of Nairobi denied that there was such a possibility, as the portions used in the vaccine were not infectious and could not revert to a live virus.     

Social impact of preventive HIV vaccine clinical trial participation: a model of prevention, assessment and intervention

Preventive HIV vaccine trial participants may experience problems related to trial participation, including difficulties with personal relationships, employment, education, health care, housing, health insurance, disability insurance, life insurance, travel or immigration. During the 19 years that the U.S.-based National Institute of Allergy and Infectious Diseases (NIAID) has conducted preventive HIV vaccine trials, we have developed a model to prevent and resolve social impact related to study participation and assist study participants who report such events. Key elements of the model include: informing potential volunteers of risks prior to enrollment; standardizing data collection methods on social impact events; reviewing and following-up on reported social impact events; assisting participants, including provision of free HIV testing to differentiate HIV infection from vaccine-induced HIV antibody; implementing broad-based and targeted community education programs for achieving community support; communicating with scientific and health care communities; and working with government agencies, non-government agencies and industry on mechanisms to address SI. This approach, established in collaboration with NIAID-funded clinical trial groups, serves as a model for prevention, assessment, monitoring, and intervention for social impact related to preventive HIV vaccine clinical trial participation. Although further research is necessary, this model could be adapted for use in different clinical trials.     

Correlates of protection, antigen delivery and molecular epidemiology: basics for designing an HIV vaccine

Major obstacles in the development of HIV vaccines are the high variability of the virus and its complex interaction with the immune system. Recent studies demonstrated, that CTLs recognizing highly conserved epitopes in the group-specific antigen are capable of controlling HIV-replication in long-term nonprogressors. Necessary consequences for novel vaccine concepts are the presentation of a large repertoire of antigenic sites as well as the stimulation of different effectors of the immune system. Accordingly, different types of recombinant HIV-1 virus-like particles (VLPs) have been constructed stimulating the induction of neutralizing antibodies and HIV-specific CD8-positive CTL responses in preclinical studies. With respect to future vaccine trials, HIV vaccine formulations may need to be tailored to the local strains circulating within a geographical region. The expert group of the joint United Nations Programme on AIDS recently identified Yunnan, a southwestern province of China, as a region, in which the HIV epidemic is starting to gain speed, resembling to the situation in Thailand 10 years ago. A molecular clone of a representative virus strain is now available for the development of innovative antigen delivery systems aiming to be evaluated in future clinical vaccine trials throughout this area.     

Informed consent by children and participation in an influenza vaccine trial.

Two hundred thirteen school children, ages six to nine, were presented the opportunity to participate in an experimental trial of swine influenza vaccine. In non-directive question and answer sessions, all groups of children except one composed only of six year olds elicited all relevant information on the details of the trial and the associated risks and benefits. Forty-six per cent of the subjects declined to participate. Letters requiring informed consent of the parents were sent to the homes of the others. Almost 15 per cent of these parents agreed to their children's participation. In this setting, children initiate their own visits to the school nurse practitioner. A significant association was found between volunteering for the study and higher use of services (but not for medical reasons). Younger children and boys, regardless of their patterns of use, were less inclined to volunteer for the experiment.     

Provision of HIV treatment in HIV preventive vaccine trials: a developing country perspective

HIV treatment for participants who become infected during HIV vaccine trials has been the focus of ethical controversy. The obligations of sponsors to ensure that participants have access to antiretrovirals have been a particular focus of this debate. This paper presents three arguments that have been made in this regard, and some of their limitations, in anticipation of HIV vaccine trials in South Africa. The first argument is that HIV risk behaviour increases in such trials, and HIV infection can be viewed as a research-related injury, justifying sponsor provision of treatment on grounds of compensation for harm. We conclude that risk-behaviour studies to date do not show general increases in risk behaviour that could constitute the basis for a general obligation. Participation may well adversely impact on risk behaviour for some individuals, and conceivably this could be demonstrated. This argument may, therefore, have merit at the individual level; however, it seems a weak platform from which to argue that sponsors should treat all HIV infections acquired during trials. The second argument is that treatment should be provided based on distributive justice. We conclude that traditional concepts of "distributive justice" in research appear limited in justifying obligations of sponsors to ensure access to antiretrovirals. Further, using research initiatives to reduce global health care inequities is controversial, and even proponents may disagree about the fairest use of finite resources. The third argument is that sponsors should ensure antiretroviral access on grounds of beneficence; namely, the maxim that if one can do something beneficial without sacrificing anything of comparable significance, it ought to be done. Thus, sponsors should provide more interventions than those minimally required to conduct the research. However, beneficence may demand levels of altruism that exceeds what is reasonable. While the latter arguments may provide stronger justifications than the first, it is difficult to use these arguments to establish that sponsor provision of antiretrovirals to infected individuals is obligatory.     

Correlates of participation in AIDS education and HIV antibody testing by methadone patients

The authors examined the factors associated with methadone patients' decisions about participating in a clinic-based AIDS prevention protocol. Despite the offer of incentives, only 27 percent attended AIDS education and only 12 percent obtained voluntary HIV antibody (ab) testing. However, AIDS education was attended by proportionately more of those who were at highest risk for AIDS because of current intravenous drug use. The availability of HIV-ab testing neither encouraged nor discouraged participation in AIDS education. Patients who were relatively more likely to choose HIV-ab testing were older, had been or were married, had plans to have children, believed the test to be useful, and believed that their counselors support their decision to be tested. Those who declined to be tested were reluctant to confront the emotional aspects of their risk status, were concerned about possible breaches of confidentiality, and doubted the value of testing. The implications of the findings for implementing AIDS prevention measures in methadone programs are discussed. Programs need either to require attendance at AIDS education or give patients an incentive to attend. HIV-ab testing should be available but should remain voluntary. A stronger medical rationale for testing is developing and may increase future participation. Methadone programs must continue to engage patients actively in AIDS risk reduction efforts.     

Exploring evidence for behavioral risk compensation among participants in an HIV vaccine clinical trial

BackgroundHIV vaccine trial participants may engage in behavioral risk compensation due to a false sense of protection. We conducted an ancillary study of an HIV Vaccine Trials Network (HVTN) vaccine efficacy trial to explore risk compensation among trial participants compared to persons who were willing to participate but ineligible based on previous exposure to the Ad5 virus (Ad5+) across three timepoints.MethodsParticipants were drawn from the Atlanta, GA site of the HVTN 505 vaccine trial. From 2011–2013, all persons who met prescreening criteria for the clinical trial and presented for Ad5 antibody testing were invited to participate in the ancillary study. Data were collected from vaccine trial participants (n = 51) and Ad5+ participants (n = 60) via online surveys across three timepoints: baseline, T2 (after trial participants received 2/4 injections) and T3 (after trial participants received 4/4 injections). Data analyses assessed demographic, psychosocial, and behavioral differences at baseline and changes at each timepoint.ResultsAt baseline, Ad5+ participants were less likely to have some college education (p = 0.024) or health insurance (p = 0.008), and were more likely to want to participate in the vaccine trial “to feel safer having unprotected sex” (p = 0.005). Among vaccine trial participants, unprotected anal sex with a casual partner (p = 0.05), HIV transmission worry (p = 0.033), and perceived chance of getting HIV (p = 0.027), decreased across timepoints.ConclusionsStudy findings suggest that persons with previous exposure to Ad5 may be systematically different from their Ad5-negative peers. Unprotected anal sex with a casual partner significantly decreased among HIV vaccine trial participants, as did HIV worry and perceived chance of getting HIV. Findings did not support evidence of risk compensation among HIV vaccine trial participants compared to Ad5+ participants.     

"Speaking the dialect": understanding public discourse in the aftermath of an HIV vaccine trial shutdown

Objectives. We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research.Methods. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008.Results. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials.Conclusions. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research.Scientific discourse, including studies and commentaries circulated in peer-reviewed medical and public health journals, reveals sometimes-contentious disagreement among biomedical researchers, public health officials, and clinicians, particularly at the vanguard of discovery. In the context of HIV vaccine research, opposing views have characterized the soundness of scientific and economic rationales for launching large-scale clinical trials^1–4 and interpretation of trial results.^5–7 It is nevertheless a basic tenet of scientific discourse that clinical trials, the majority of which do not result in an efficacious product, are mechanisms to inform evolving discovery.Contested clinical trials and biomedical outcomes also may constitute controversial social phenomena. Yet throughout a history of international HIV chemoprophylaxis trial shutdowns and sometimes-acerbic debate,^4,8,9 considerably less attention has focused on the social processes and outcomes of clinical trials; these too might be used to advance an evolving social science of biomedical HIV prevention research, including evidence to support critical processes of knowledge translation and community engagement.^9,10     

Economic costs of HIV infection: an employer's perspective

The introduction of highly active antiretroviral therapy has proven highly effective in treating patients with HIV/AIDS. However, the high cost of the advanced antiretroviral therapy has led to increased financial constraints on both patients and payers. From business firms'perspective, especially those with operations in developing countries, it is crucial to determine the long-term economic cost implications of alternative employment and benefit policies for HIV-infected workers or those at high risk for the disease. A simulation model is developed to predict the comprehensive lifetime economic costs of HIV-infected workers to an employer. This model employs age,CD4⁺ cell counts,and plasma HIV-1 RNA level as major predictors of the disease progression and patient survival in the determination of various cost functions.Major cost components considered include direct expenses on health insurance premium,life insurance premium, short-term disability benefits, long-term disability benefits, hiring/training expenses, and indirect costs resulting from reduced or lost productivity at work. An individual model and a group model are derived to estimate the costs of an individual and a group of HIV-infected patients, respectively.Over a 10-year period, following the nonadvanced antiretroviral treatment regimen, the group model predicts that the total lifetime cost of an HIV-infected worker can be as high as U.S. $90,000 to his/her employer, of which $60,000 would be various explicit costs and $30,000 lost work productivity. Sensitivity analysis further demonstrated that changes in the initial level of age,CD4⁺ cell count, HIV-1 RNA viral load,CD4⁺ cell decline rate, and the costs of medical care influence the dynamics of the cost functions. HIV infection can result in sizable economic costs to an employer over the lifetime course of an infected employee if not treated with the advanced antiretroviral therapy.These cost estimates provide a rational economic basis for an employer to optimally assess the longrun costs and benefits of alternative employment and insurance policies in the care of employees with HIV infection. Gordon G. Liu Pharmaceutical Policy and Evaluative Sciences, Beard Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA, e-mail: ggliu@unc.edu     

Willingness to participate in HIV vaccine trials: the impact of trial attributes

OBJECTIVES: To assess willingness to participate (WTP) in hypothetical Phase III preventive HIV vaccine trials, and the impact of trial attributes on WTP, among low socioeconomic, ethnically diverse adults from communities at elevated risk for HIV infection. METHOD: Participants (n=123; median age=38; 69% male; 37% Latino; 14% African-American) were recruited in Los Angeles in 2003 using multi-site, venue-based sampling. WTP was assessed for eight hypothetical HIV vaccine trials that varied across seven dichotomous attributes, using a 2(7-4) fractional factorial experimental design. Individual-specific impact of vaccine trial attributes on WTP was estimated using within-individual ANOVA and then meta-analyzed across individuals. RESULTS: Mean WTP for eight hypothetical vaccine trials ranged from 1.74 to 3.81 (1=highly unlikely, 5=highly likely). Lower WTP was associated with vaccine-induced infection risk (impact=0.88, p<0.0001), false HIV-positives (0.53, p<0.0001), no provision of free HIV medications (0.52, p<0.0001), and longer trial duration (0.27; p=0.0002). CONCLUSION: HIV vaccine trial attributes may strongly influence WTP. Although existing candidate vaccines cannot cause HIV infection, perceptions of risk may impede WTP. Eliciting trial preferences and concerns prior to trial implementation may enable accommodation of participant preferences and support tailored interventions to address concerns and misconceptions to facilitate enrollment in safe and ethical trials among vulnerable communities.     

Influences on physical activity participation among Latinas: an ecological perspective

Objectives: To explore intrapersonal, social environmental, and physical environmental influences that promote or impede total physical activity (TPA) among Latinas in Lee County, Florida. Methods: Indepth interviews (n=41) and face-to-face surveys (n=358). Results: Women who worked outside the home had positive attitudes about activity, perceived themselves to have access to activity facilities, and perceived their neighborhood to be safe reported higher TPA. Women who had more education and whose health information source was radio had lower TPA. Conclusions: Intrapersonal and environmental factors influence TPA levels among Latinas. Segmenting Latina groups using these factors may promote more involvement in physical activity through targeted programs and messages.     

Cognitive factors and willingness to participate in an HIV vaccine trial among HIV-negative injection drug users

This cross-sectional study involving a cohort of injection drug users (IDU) examined the relationship between cognitive factors (HIV treatment optimism, self-efficacy and knowledge of vaccine trial concepts) as well as risk factors for seroconversion, and willingness to participate (WTP) in a preventive phase 3 HIV vaccine trial. Willingness to participate overall was 56%. In a multivariate analysis, for a 20-unit increase in a 100-point composite scale, self-efficacy was positively related to WTP (adjusted odds ratio [AOR] = 1.95, 95% CI = 1.40–2.70). HIV treatment optimism and knowledge of vaccine trial concepts were unrelated to WTP. Aboriginal ethnicity (AOR = 3.47, 95% CI = 1.68–7.18) and a higher educational level (≥high school) (AOR = 1.96, 95% CI = 1.07–3.59) were positively related to WTP. This study provides information on WTP for an HIV vaccine trial. Limitations and future directions are also discussed.     

"Once Bitten, Twice Shy": participant perspectives in the aftermath of an early HIV vaccine trial termination

The Step Study phase IIb HIV-1 vaccine trial was terminated early due to futility; subsequent analyses revealed increased susceptibility to HIV infection among a subset of test vaccine recipients. We conducted a mixed methods investigation, including a brief, self-administered baseline questionnaire and in-depth, semi-structured, 1-h interviews after unblinding, to explore experiences and perspectives among trial participants and key informants. Interviews were digitally recorded, transcribed, and analyzed using NVivo and thematic techniques. Forty-eight trial participants (46 gay/bisexual men) completed baseline surveys; 15 (14 gay/bisexual men) engaged in post-trial interviews. Participants indicated surprise and disappointment about the early trial termination and unexpected risks. Some articulated understanding the uncertainties of clinical trials, steadfast support and willingness to participate in the future; others reported greater risks than they deemed acceptable and unlikelihood of volunteering again. A few indicated mistrust of trial sponsors and ethics. Participants’ most profound criticism was not about unexpected results, but perceived delays in unblinding and gaps in post-trial dissemination of information. Future HIV vaccine trials may benefit from increased emphasis on: (1) communication mechanisms among participants, investigators and trial sponsors, and (2) post-trial dissemination of information and psychosocial support.     

Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

Background

Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability.

Methods

HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n = 1225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling.

Results

Exploratory factor analysis across 20 items revealed four distinct factors – mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination – with acceptable reliability coefficients for each subscale (Cronbach's α range 0.61–0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (odds ratio (OR) = 1.49; 95% CI = [1.18, 1.89]; p = 0.001) and altruistic vaccination (OR = 1.40; 95% CI = [1.14, 1.71]; p = 0.001) were significantly and positively associated with HIV vaccine acceptability.

Conclusions

We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions to support recruitment and mitigate risk compensation.