Preventive HIV Vaccine Trials Research Articles

Why did I participate in an HIV vaccine study? Experiences of participation in the first phase II HIV vaccine trial in Mozambique: An ancillary study using a mixed-method approach

IntroductionThis study recognized the lack of information regarding recruitment and retention factors associated with implementing HIV vaccine trials from the perspective of de facto participants. It aimed to describe the motives and experiences of 31 young adults who participated in a phase II HIV vaccine clinical trial conducted in Maputo, Mozambique. MethodsThis was an ancillary study with a mixed-method approach that employed a convergent design, combining both quantitative and qualitative methodologies. Data collection involved questionnaire surveys, in-depth interviews, and focus group discussions. Participants were assessed before and after learning whether they received the experimental vaccine or placebo. Thematic analysis was used for qualitative data, while descriptive analysis and statistical tests such as Fischer’s test and McNemar’s exact test were applied to quantitative data. The study also utilized the Health Belief Model to understand the decision-making process of participating in an HIV vaccine study. ResultsMost of our participants were young females, single, with limited financial resources. Participants joined the trial with the belief that they had a unique opportunity to help the fight against HIV and contribute to the research for the discovery of an HIV vaccine. Positive experiences related to trial participation include gaining knowledge about HIV and personal health and receiving risk reduction counseling. Participants reported blood collection as a negative experience and that they suffered social harm because of trial participation. Participants felt abandoned after the trial ended. ConclusionPreventive HIV vaccine trials should integrate a social-behavioral component to assess reasons for participation and refusal in real-time. Providing ongoing personal attention is crucial for young individuals who have committed 1–2 years to trial participation, extending beyond the trial period. Implementing tailored strategies for HIV risk assessment and reduction during and after the trial is essential. Addressing these factors can enhance preventive HIV vaccine trial implementation.

Exploring a community’s understanding of HIV vaccine‑induced seropositivity in a South African research setting

The high HIV prevalence and incidence in South Africa makes it suitable for recruitment of participants for large-scale HIV preventive vaccine trials. However, fear of vaccine-induced seropositivity (VISP) may be a barrier for community acceptability of the trial, for volunteers to participate in HIV preventive vaccine trials and for uptake of an efficacious vaccine. Prior to 2015, when the first phase 1 safety HIV vaccine trial was undertaken at Setshaba Research Centre, Soshanguve, the local community stakeholders and healthcare workers were naive about HIV vaccine research and HIV preventive vaccines. To explore knowledge and perceptions regarding VISP among community stakeholders and healthcare workers in peri-urbanb Soshanguve, Tshwane. Using a quantitative-qualitative mixed-methods study design, surveys (n=50) and in-depth interviews (n=18) were conducted during July - August 2015. Participants included community stakeholders, community advisory board members and healthcare workers, who were >18 years old and had attended community educational workshops during September 2014 - May 2015. Audio recordings of interviews were transcribed verbatim and coded using content thematic analysis. Data were further analysed by sex, age and educational level. Of a maximum score of 2 on knowledge on VISP, the 50 survey participants (mean age 33.78 years; 45 females) obtained an average of 0.88 (44%). Of 17 in-depth interviewees (one interview could not be transcribed; mean age 30.9 years; 12 females), 8 (47%) displayed some knowledge about VISP, of whom only 5 defined VISP correctly. Women were more knowledgeable about VISP than men; 5 of 12 women (42%) came close to defining VISP correctly, while none of the 5 men did so. The main fear of trial participation expressed by most participants (n=6) was testing HIV-positive as a result of the vaccine. While some participants believed that the community's perceptions of VISP would negatively affect HIV vaccine trial support and recruitment efforts, others noted that if trial participants understand the concept of VISP and are part of support groups, then they would have the information to combat negative attitudes within their community. Most participants had an inaccurate and incomplete understanding of VISP. Many feared testing HIV-positive at clinics; therefore, education on improving a basic understanding of how vaccines work and why VISP occurs is essential. In addition, assessing participant understanding of HIV testing, transmission and VISP is critical for recruitment of participants into HIV vaccine trials and may improve acceptability of an HIV preventive vaccine.

Shifts in UNAIDS ethics guidance and implications for ethics review of preventive HIV vaccine trials.

IntroductionA major change in the ethics framework for preventive HIV vaccine trials worldwide is the release of the UNAIDS 2021 ethical considerations in HIV prevention trials. This new guidance comes at an exciting time when there are multiple HIV vaccine efficacy trials in the field. Research Ethics Committees (RECs) or Institutional Review Boards are a most likely audience for these guidelines. Our objective is to highlight shifts in ethics recommendations from the earlier 2012 UNAIDS guidance.DiscussionWe review recommendations related to four key issues, namely standard of prevention, post‐trial access to safe and effective vaccines, enrolment of adolescents and enrolment of pregnant women. We outline implications and make recommendations for the ethics review process, including suggested lines of inquiry by RECs and responses by applicants.ConclusionsThere have been several shifts in the UNAIDS ethics guidance with implications for HIV vaccine researchers submitting applications for initial ethics review or re‐certification, and for RECs conducting such reviews. This review may assist RECs in a more efficient and consistent application of ethics recommendations. However, additional tools and training may further help stakeholders comply with new UNAIDS ethics recommendations during protocol development and ethics review.

Social Impacts Among Participants in HIV Vaccine Trial Network (HVTN) Preventive HIV Vaccine Trials.

Given the persistent stigma and discrimination against HIV worldwide, preventive HIV vaccine trials face unique challenges. Negative social impacts (NSIs)-problems that HIV vaccine trial participants face in many different spheres of their lives related to trial participation-have received a great deal of attention. Beneficial social impacts (BSIs)-perceived benefits experienced by a participant and resulting from their trial participation-are a critical component of participants' experiences, yet they have received little attention. All HIV Vaccine Trials Network trial participants for whom social impact data were available-8347 participants in 13 countries who enrolled in 48 phase 1, 2a, and 2b trials. A cross-protocol analysis to assess self-reported BSIs and NSIs related to participating in a preventive HIV vaccine trial. Data were obtained from 48 completed HIV Vaccine Trials Network vaccine trials from December 2000 to September 2017. Overall, 6572 participants (81%) reported at least one BSI, and 686 participants (8%) reported 819 NSI events. Altruism/feeling good helping others was the BSI most often endorsed by study participants (43%), followed by receiving risk-reduction counseling (30%). Most NSI events (81%) were reported by US/Swiss participants, and most (79%) trial-related NSIs were negative reactions from friends, family, and partners. Of the NSIs reported, 7% were considered to have a major impact on the participant's quality of life. Our results underscore the relatively common experiences of BSIs among preventive HIV vaccine trial participants and mirror the results of other studies that find infrequent reports of NSIs.

Using Mobile Technology (pMOTAR) to Assess Reactogenicity: Protocol for a Pilot Randomized Controlled Trial.

BackgroundAccurate safety monitoring in HIV vaccine trials is vital to eventual licensure and consequent uptake of products. Current practice in preventive vaccine trials, under the HIV Vaccine Trials Network (HVTN), is to capture related side effects in a hardcopy tool. The reconciliation of this tool, 2 weeks after vaccination at the safety visit, is time consuming, laborious, and fraught with error. Unstructured Supplementary Service Data (USSD), commonly used to purchase airtime, has been suggested for collection of safety data in vaccine trials. With saturated access to mobile phones in South Africa, this cheap, accessible tool may improve accuracy and completeness of collected data and prove feasible and acceptable over the hardcopy tool.ObjectiveThe objective of our study is to develop and implement a USSD tool for real-time safety data collection that is feasible and acceptable to participants and staff, allowing for a comparison with the hardcopy tool in terms of completeness and accuracy.MethodsThis feasibility study is being conducted at a single study site, the Centre for the AIDS Programme of Research in South Africa eThekwini Clinical Research site, in South Africa. The feasibility study is nested within a parent phase 1/2a preventive HIV vaccine trial (HVTN 108) as an open-label, randomized controlled trial, open to all consenting parent trial participants. Participants are randomly assigned in a 1:1 ratio to the hardcopy or USSD tool, with data collection targeted to the third and fourth injection time points in the parent trial. Online feasibility and acceptability surveys will be completed by staff and participants at the safety visit. We will itemize and compare error rates between the hardcopy tool and the USSD printout and associated source documentation. We hypothesize that the USSD tool will be shown to be feasible and acceptable to staff and participants and to have superior quality and completion rates to the hardcopy tool.ResultsThe study has received regulatory approval. We have designed and developed the USSD tool to include all the data fields required for reactogenicity reporting. Online feasibility and accessibility surveys in both English and isiZulu have been successfully installed on a tablet. Data collection is complete, but analysis is pending.ConclusionsSeveral HIV preventive vaccine trials are active in Southern Africa, making tools to improve efficiencies and minimize error necessary. Our results will help to determine whether the USSD tool can be used in future vaccine studies and can eventually be rolled out.Trial RegistrationClincalTrials.gov NCT02915016; https://clinicaltrials.gov/ct2/show/NCT02915016 (Archived by WebCite at http://www.webcitation.org/71h0cztDM)Registered Report IdentifierRR1-10.2196/9396

Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials

BackgroundThe evaluation of durable immune responses is important in HIV vaccine research and development. The efficiency of such evaluation could be increased by incorporating predictors of the responses in the statistical analysis. In this paper, we investigated whether and how baseline demographic variables and immune responses measured two weeks after vaccination predicted durable immune responses measured six months later. MethodsWe included data from seven preventive HIV vaccine regimens evaluated in three clinical trials: a Phase 1 study of four DNA, NYVAC and/or AIDSVAX vaccine regimens (HVTN096), a Phase 2 study of two DNA and/or MVA vaccine regimens (HVTN205), and a Phase 3 study of a single ALVAC/AIDSVAX regimen (RV144). Regularized random forests and linear regression models were used to identify and evaluate predictors of the positivity and magnitude of durable immune responses. ResultsWe analyzed 201 vaccine recipients with data from 10 to 127 immune response biomarkers, and 3–5 demographic variables. The best prediction of participants’ durable response positivity based on two-week responses rendered up to close-to-perfect accuracy; the best prediction of participants’ durable response magnitude rendered correlation coefficients between the observed and predicted responses ranging up to 0.91. Though prediction performances differed among biomarkers, durable immune responses were best predicted by the two-week response level of the same biomarker. Adding demographic information and two-week response levels of different biomarkers provided little or no improvement in the predictions. ConclusionsFor some biomarkers and for the vaccines we studied, two-week post-vaccination responses can well predict durable responses six months later. Therefore, if immune response durability is only assessed in a sub-sample of vaccine recipients, statistical analyses of durable responses will have increased efficiency by incorporating two-week response data. Further research is needed to generalize the findings to other vaccine regimens and biomarkers.Clinicaltrials.gov identifiers: NCT01799954, NCT00820846, NCT00223080.

Current ethical issues in HIV/AIDS research and HIV/AIDS care.

HIV/AIDS is a global public health concern with more than 30 million deaths having been reported. Over 70% of the 35 million people with HIV/AIDS live in sub-Saharan Africa. The current available antiretroviral treatments are limited because they do not cure but slow the progression of disease. Therefore, care and treatment for HIV/AIDS and its related research, especially in HIV-preventive vaccine trials, require stringent ethical guidelines because of the vulnerability of the affected individuals as it with all clinical trials. These guidelines should incorporate the basic principles in ethics which include autonomy of individuals, beneficence, non-malfeasance and justice in the care and participation of individuals in research. With at least one in five African adults infected with the disease living in sub-Saharan Africa, this review will discuss the current ethical issues in HIV care and HIV research based on the South African context as well as exploring some of the issues globally.

Representation of Latinos and Blacks in screening for and enrollment into preventive HIV vaccine trials in New York City

IntroductionIn the United States, Latinos and Blacks are disproportionately affected by HIV/AIDS, but have been underrepresented in HIV vaccine trials. We assessed screening and enrollment of Blacks and Latinos for preventive HIV vaccine trials conducted in New York City, 2009–2012. MethodsA retrospective analysis was conducted among 18–50 year old men and transgender women screening for four preventive phase 1 and 2 HIV vaccine trials. Demographic, recruitment, and behavioral/medical eligibility data and outcome of screening were examined. To determine factors associated with enrollment, a multivariable logistic regression analysis was performed. ResultsAmong 6077 individuals who provided contact information, 2536 completed a phone pre-screen. 96 (1.6% of recruitment contacts) enrolled. Latinos were 35.7% of recruitment contacts, but 17.7% of those enrolled, whereas Blacks were 22.5% and 32.3%, respectively. Among all Latinos, nearly one third were excluded for being uncircumcised, an eligibility criterion for several studies. In multivariable analysis among potentially eligible potential participants, controlling for age and recruitment method, Latinos were less likely than Whites to enroll in a preventive HIV vaccine trial (aOR 0.52, 95% CI 0.28–0.95) whereas Blacks were as likely as Whites (aOR 0.99, 95% CI 0.59–1.67). Individuals recruited through print advertisements, social media/internet, referral, and other modes were more likely to enroll compared to those recruited through in-person outreach, controlling for age and race/ethnicity. ConclusionsTargeted outreach has led to substantial inclusion of Latinos and Blacks, with Blacks comprising almost a third of those enrolled in these preventive HIV vaccine trials. Latinos, however, were less likely to enroll compared to Whites. Circumcision status as an eligibility criterion partly accounts for this, but further studies are warranted to address the reasons Latinos decide not to participate in preventive HIV vaccine trials.

Use of placebos in Phase 1 preventive HIV vaccine clinical trials

Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives.

Lessons Learned from HIV Vaccine Clinical Efficacy Trials

The past few years have witnessed many promising advances in HIV prevention strategies involving preexposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end.

Long-Term Persistence of Vaccine-Induced HIV Seropositivity in Healthy Volunteers

Objectives: To assess the long-term serological impact of HIV preventive vaccine trial participation, vaccineinduced HIV seropositivity (VISP) was evaluated and related factors were investigated. The anti-HIV antibody reactivity ratio distribution was estimated. Methods: ANRS COHVAC is an open national prospective multicentre cohort study including healthy volunteers who received at least one dose of vaccine candidate of ANRS HIV preventive vaccine trials since 1992. VISP was studied in a cross-sectional study at the time of the cohort’s initial visit, starting in 2008. Anti-HIV antibody detection was performed using the ABBOTT ARCHITECT® HIV Ag/Ac Combo Enzyme Immunoassay (EIA) in a centralized laboratory. A ratio greater than or equal to 1 was considered to define HIV seropositivity. Results: 293 participants were evaluated for a median period of 6 years (range: 2-18 years) after their inclusion in vaccine preventive trials. The frequency of VISP was estimated at 7.2% (21 out of 293) for all volunteers, and 69.0% (20 out of 29) for volunteers who received recombinant HIV-1 envelope protein, after a median period of 16.6 years after immunization (range: 16.3-18.4). The ARCHITECT test ratio among positive volunteers was low, with a median of 3.02 (range: 1.02 -14.04). Conclusion: Healthy volunteers should be informed of possible VISP persistence for nearly 17 years, following HIV envelope vaccination inducing antibody responses. A single, routine serology test is unable to differentiate between VISP and a recent HIV infection. The combination of different technologies, applicable to resource-limited settings, is needed to distinguish vaccine-induced seropositivity from an HIV infection.

Inclusion of adolescent girls in HIV prevention research – an imperative for an AIDS‐free generation

Recent scientific advances centred on the use of anti-retrovirals (ARVs) – both prophylactically to prevent HIV acquisition (pre-exposure prophylaxis, or PrEP) and for treatment to minimize onward transmission (treatment as prevention, or TasP) – have led to a new-found optimism for control of the HIV/AIDS epidemic and the possibility of creating an “AIDS-free generation”. In order to translate this optimism into reality, large and sustained reductions in incident HIV infections are required. Several models have projected that with substantial programmatic scale-up of the new prevention agenda, such requirements can be satisfied. However, these models typically assume a uniform efficiency for interventions in reducing incident infections across populations, and neglect to consider their current unavailability to a key population driving the epidemic at its epicentre: adolescent girls. (Published: 8 March 2014) Citation: Abdool Karim Q and Dellar R. Journal of the International AIDS Society 2014, 17 :19075 http://www.jiasociety.org/index.php/jias/article/view/19075 | http://dx.doi.org/10.7448/IAS.17.1.19075

Motivators to Participation in Actual HIV Vaccine Trials

An examination of actual HIV vaccine trials can contribute to an understanding of motivators for participation in these studies. Analysis of these motivators reveals that they can be categorized as social and personal benefits. Social benefits are generally altruistic, whereas personal benefits are psychological, physical, and financial. In this systematic review, the authors performed a literature search for actual preventive HIV vaccine trials reporting motivators to participation. Of studies conducted in the Organization for Economic Co-operation and Development (OECD) countries, the authors retrieved 12 studies reporting on social benefits and seven reporting on personal benefits. From the non-OECD countries, nine studies reported on social benefits and eight studies on personal benefits. Social benefits were most frequently described on macroscopic, altruistic levels. Personal benefits were most frequently psychological in nature. Rates of participation were compared between the OECD and the non-OECD countries. Knowledge of actual motivators in specific countries and regions can help target recruitment in various types of actual HIV vaccine trials.

Reasons for Not Participating in a Phase 1 Preventive HIV Vaccine Study in a Resource-Rich Country

Dear Editor, One of the limitations in conducting phase 1 preventive HIV vaccine trials in a resource-rich country is the difficulty in recruiting volunteers. There are currently 34 million people living with HIV and each year 2.7 million people become newly infected and 1.8 million people die of AIDS. Preventive HIV vaccine investigation is a critical path in developing a long-term strategy to control the worldwide HIV epidemic. Research efforts over the last two decades to develop a preventive HIV vaccine have showed that this is a particularly difficult objective. To date, over 200 phase 1–3 HIV vaccine trials have been conducted or are ongoing but only 3 have reached phase 3. Only one HIV vaccine in a phase 3 study demonstrated a modest efficacy when compared with placebo. Therefore, multiple trials are needed to find an effective HIV vaccine and greater efforts for any promising immunogen to reach phase 1 clinical trials has been proposed. It is estimated that over 35,000 volunteers will be required per year for phase 1–3 HIV vaccine trials worldwide to achieve this goal. Several studies have focused on the hypothetical willingness-to-participate or enrollment efficiency and have identified the most frequent reasons cited for declining HIV trial enrollment. Despite the growing literature on this issue, there are few data on barriers to participation in low risk volunteers willing to participate in phase 1 preventive HIV vaccine. The first phase 1 HIV vaccine clinical trial conducted in Spain, RISVAC-02, needed to recruit 30 HIV-uninfected volunteers in Spain. RISVAC-02 was a double-blinded, randomized placebocontrolled phase 1 HIV vaccine trial conducted in two Spanish clinical centers in Madrid and Barcelona. The study was approved by the institutional ethical review board and by the Spanish Regulatory Authorities. Details of the design of the study are published elsewhere. Inclusion criteria were age between 18 and 55 years, being at low risk of HIV-1 infection, agreeing to use an effective method of contraception from 14 days prior to the first vaccination until 4 months after the last immunization, and consent to HIV and sexually transmitted disease (STD) testing. The exclusion criteria were pregnancy or lactation, serious clinical problems, receiving a live attenuated vaccine 60 days before or any vaccine 14 days before screening, receiving any blood product or gamma-globulins 4 months before screening, participating in any other clinical trial 30 days before enrollment, history of several local or systemic vaccine reactions, and HIV/hepatitis B virus (HBV)/ hepatitis C virus (HCV)/syphilis infection. We analyzed demographics, recruitment source, sexuality, motivation to participate, or discontinuation of all healthy volunteers from the first contact with us to the baseline RISVAC-02 study. Different strategies and various approaches for recruitment of potential volunteers were used. Advertisements in mass media such as national and local newspapers, medical journals, HIV-related magazines, and TV interviews were conducted. E-mails were sent to different organizations: HIV/ AIDS NGOs, gay community associations, universities, hospitals, and others social networks. Informative posters were distributed in the cities of Madrid and Barcelona. Individuals who responded and provided a telephone number or an e-mail address were contacted and given further information. If they were interested we invited them to participate in a prescreening interview were they answered a survey that was conducted by trained nursing staff in a personal interview. Demographics, clinical history, lifestyle and risk factors, how they found out about the study and reasons for participating were obtained through an open/closed-ended questionnaire. If individuals were eligible and interested in participating, they were booked for a screening appointment. Informed consent was obtained from all the subjects. Those patients who agreed and fulfilled the inclusion criteria were enrolled. SPSS version 17 (SPSS, Inc., Chicago, IL) was used for analysis. Descriptive statistics and cross-tabulations were generated for all the variables of interest. Continuous variables were compared between groups with the Student’s t test or the non-parametric Mann-Whitney U test. Categorical variables were compared between groups with the v or Fisher’s exact tests. p value of £ 0.05 was considered significant. A total of 356 volunteers who responded to our campaign and sent a telephone number or an e-mail address were contacted and invited to a first interview. Seventy-five subjects

Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events

Background Recently, more clinical trials are being conducted in Africa and Asia, therefore, background morbidity in the respective populations is of interest. Between 2000 and 2007, the International AIDS Vaccine Initiative sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub-Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers.Objective To assess background morbidity as reflected by unsolicited adverse events (AEs), unrelated to study vaccine, reported in clinical trials from four continents.Methods All but three clinical trials were double-blind, randomized and placebo-controlled. Study procedures and data collection methods were standardized. The frequency and severity of AEs reported during the first year of the trials were analyzed. To avoid confounding by vaccine-related events, solicited reactogenicity and other AEs occurring within 28 d after any vaccination were excluded.Results In total, 2134 AEs were reported by 76% of all participants; 73% of all events were mild. The rate of AEs did not differ between placebo and vaccine recipients. Overall, the percentage of participants with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and India (65%), while the percentage of participants with AEs of moderate or greater severity was similar in all regions except India. In all regions, the most frequently reported AEs were infectious diseases, followed by gastrointestinal disorders.Conclusions Despite some regional differences, in these healthy participants selected for low risk of HIV infection, background morbidity posed no obstacle to clinical trial conduct and interpretation. Data from controlled clinical trials of preventive interventions can offer valuable insights into the health of the eligible population.

Barriers to Volunteer Enrollment in HIV Preventive Vaccine Clinical Research Trials: A Review of the Literature

Attempting to enroll volunteers into a clinical research study often presents a challenge to the investigative team. Potential subjects often look on the experience with suspicion; they might fear being treated like ‘‘guinea pigs.’’ Many preconceived biases about participating in research stem from one particular clinical study, the infamous Tuskegee syphilis experiment. In this study, which started in 1932 and lasted 40 years, 600 Black men (300 with syphilis and 201 without syphilis) from a rural area of Alabama were told by researchers that they were being treated for ‘‘bad blood,’’ a local term used to describe several ailments, including syphilis, anemia, and fatigue. In truth, they did not receive the proper treatment to cure syphilis. When the study was reviewed, an investigative panel found (a) no evidence that researchers had informed the participants about the study or its real purpose, (b) that the men had been misled and had not been given all the facts required to provide informed consent, and (c) nothing to show that subjects were ever given the choice of quitting the study, even when penicillin became the drug of choice for syphilis in 1947 (Centers for Disease Control and Prevention, 2009). Although codes have since been implemented to prevent such unethical behavior from recurring and thousands of studies have been conducted without incident, the fear of being harmed still haunts potential volunteers. When testing a preventive vaccine against HIV, the challenges to recruit, enroll, and retain volunteers for clinical trials become even more difficult because many communities have not been adequately informed or rather have been misinformed about HIV vaccine research, resulting in a basic mistrust of this research. Knowing the factors that influence enrollment of volunteers into HIV vaccine research can greatly affect recruitment and retention of volunteers. As McCluskey, Alexander, Larkin, Murguia, and Wakefield (2005) wrote, ‘‘A promising vaccine candidate without the volunteers needed to test it, or a vaccine that is not trusted by the people it is meant to benefit, will impair long-term success’’ (p. 650). The purpose of this article is to explore factors that deter recruitment of volunteers into HIV preventive vaccine trials.

HIV vaccine trial willingness among injection and non-injection drug users in two urban centres, Barcelona and San Francisco

Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%).

HIV-1 Incidence Rates and Risk Factors in Agricultural Workers and Dependents in Rural Kenya: 36-Month Follow-Up of the Kericho HIV Cohort Study

Incidence data from prospective cohort studies using rigorous laboratory methods are important in designing and evaluating HIV vaccine and therapeutic clinical trials and health care programs. We report 36-month HIV-1 incidence rates and demographic and psychosocial risks from the Kericho cohort in rural Kenya's southern Rift Valley Province. Thirty-six month, prospective, closed, observational cohort study of adult plantation workers and dependents followed biannually. HIV-1 incidence rates per 100 person-years (py) were calculated, and Cox regression analyses were used to estimate hazards ratios (HR) associated with seroconversion. Two thousand four hundred volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated. Twenty-nine new HIV cases were identified in year 1 of follow-up, which increased to cumulative totals of 49 and 63 cases in years 2 and 3, respectively. The corresponding 1-, 2-, and 3-year incidence rates were 1.41 [95% confidence interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00 (95% CI = 0.77-1.28) per 100 py. Risk factors associated with HIV seroconversion included the following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than once (HR = 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32; 95% CI = 0.17-0.60), history of sexually transmitted infection (HR = 2.40; 95% CI = 1.09-5.26), history of substance abuse during sex (HR = 2.44; 95% CI = 1.16-5.13), and history of transactional sex (HR = 3.30; 95% CI = 1.79-6.09). HIV-1 incidence rates were relatively low in adult plantation workers and dependents in rural Kenya. Cohorts including higher risk populations (eg, commercial sex workers) warrant consideration for regional HIV preventive vaccine trials. Even low incidence, well-described cohorts generate valuable epidemiological clinical trial data.

The Potential Role of Biomarkers in HIV Preventive Vaccine Trials

Successful conduct of HIV vaccine efficacy trials entails identification and enrollment of at-risk populations, assessment of appropriate end points as measures of vaccine efficacy for prevention of HIV acquisition, and amelioration of disease course among infected vaccinees, as well as identification of potential confounders or effect modifiers. Although not invariably useful and bringing their own cost in terms of measurement and validation, a variety of biomarkers may aid at each stage of trial conduct. A review of selected articles, chosen based on quality, relevance of the biomarker to HIV vaccine trials, and availability of the publication, was conducted. The authors also drew experience from current trials and other planned or ongoing trials. Biomarkers are available to assess HIV incidence in potential study populations, but care is needed in interpreting results of these assays. During trial conduct, sexually transmitted infections such as herpes simplex virus type 2 may act as effect modifiers on primary and secondary end points, including HIV incidence and set point viral load. The utility of sexually transmitted infection biomarkers will likely depend heavily on local epidemiology at clinical trial sites. Analyses from recent large HIV vaccine efficacy trials point to the complexities in interpreting trial results and underscore the potential utility of biomarkers in evaluating confounding and effect modification.

Engaging Members of African American and Latino Communities in Preventive HIV Vaccine Trials

African Americans (AAs) and Latinos in United States bear a disproportionate burden of HIV infection, yet remain underrepresented in HIV vaccine trials. The success in engaging and enrolling AAs and Latinos in phase 1 and phase 2 vaccine trials at 2 research sites in New York City is described. A retrospective analysis of 1683 HIV-uninfected individuals who completed > or = 1 stage of the screening process from 2002 to 2006. Data on sociodemographic, behavioral characteristics, medical eligibility, and enrollment in National Institutes of Health-sponsored vaccine trials were collected. 7.5% of screening participants completed enrollment; 33% were AAs, 24% Latinos. The proportion of enrollees did not differ significantly by race/ethnicity. Low-risk vs. high-risk AAs (49% vs. 23%, P = 0.006) and high-risk vs. low-risk Latinos (31% vs. 13%, P = 0.006) were more likely to enroll. Among them, loss to follow-up was the most common reason for not completing screening. In multivariate analysis, older participants, high-risk men, and high-risk women were more likely to complete enrollment. Once potential minority participants are identified and engaged in the screening process, it is possible to enroll them at rates comparable to white participants. Experience at these sites suggests that the challenge in achieving high rates of minority participation is in increasing the initial pool of candidates prescreening for HIV vaccine studies.