HIV Vaccine Clinical Trials Research Articles

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection.

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.

Substance use patterns of HVTN phase I clinical trial participants: Enrollment, risk reduction counseling and retention

BackgroundThe primary objectives of HIV Vaccine Trials Network (HVTN) phase 1 preventive HIV vaccine clinical trials are to assess safety and immune response to study products. Participant alcohol and drug use may affect adherence, retention, and risk of HIV infection. Data on the effects of substance use are limited to medical care compliance and treatment adherence in HIV infected participants. To our knowledge, there are no data assessing substance use and retention in these vaccine trials. MethodsWe performed a meta-analysis on substance use and its impact on retention in HVTN phase I trials that recruited participants demonstrating lower risk profiles for HIV infection. Our analysis included data from 10 HVTN phase 1 clinical trials conducted between February 2009 and September 2014 in the Americas and Switzerland that utilized the identical interviewer-administered behavioral risk assessment questionnaire to capture participant self-report of substance use in the previous six months. Chi Square tests were used to assess statistical differences between variables. ResultsAmong the 964 participants, 170 (18%) missed a clinic visit and 78 (8%) terminated early from clinic follow-up; 75/774 (10%) on studies with multiple vaccination timepoints did not complete their vaccinations. Neither frequency of alcohol use, binge drinking, marijuana, nor other drug use reported at screening visits were associated with the three adherence/retention measures. Binge drinking was associated with higher rates of unprotected sex while drunk (p < .001). ConclusionsLight to moderate alcohol use does not negatively impact adherence or retention in phase I clinical trials. Based on these screening data and the low infection rate of participants during the trial period, the screening process for participation in HVTN phase 1 trials has largely been successful in enrolling and retaining individuals with lower risk profiles. Focusing on binge drinking and increased HIV/STI risk during risk reduction counseling may be warranted.

Strategies for Good Retention Rates in HIV Exposed Sero-Negatives (HESN) Individuals: Important Consideration for HIV Biomedical Prevention Trials in Nigeria

Background: Retention in clinical trials is critical for the accumulation of data over time and retaining enough power for comprehensive analysis. We document for the first time the retention rates and factors associated with retention among a cohort of HIV exposed seronegative (HESN) person in a discordant relationship. Understanding these factors will provide valuable cues for maintaining high retention rates in future HIV biomedical prevention studies in this cohort. Aim: We aimed to document retention rates and associated factors relevant in conducting future HIV prevention studies using a cohort of HIV exposed sero-negative individuals. Method: We conducted a prospective cohort study to enroll HESN persons in discordant relationship based on established inclusion criteria that includes: Established sero-discordance with at least 3 months in the relationship; above 18 years and willingness to be followed up. Relevant ethical approvals were obtained. Following informed consent at enrollment, standardized questionnaires on risk behavior and factors that may affect retention were administered at enrollment and during the 2 years follow-up. This was spread over 10 follow-up visits to mimic phase a 2b HIV vaccine clinical trial follow up and duration. In addition, clinical examinations were done and samples collected for safety lab during the follow up visits. Estimation of CD4 and viral load was also done for the HIV+ partners of HESN study participants. Results: Six hundred and sixty HESN persons were screened and 534 (81%) enrolled (i.e. month 0) and followed up. There was a decline in retention from 96% at month 1 (visit 1) to 78% at month 24 (Visit 10). Sharpest drop out from the study occurred at month 1 (20%) and month 15 (14%) follow-up visits. Inability to reach study participants, unwillingness of study participants to continue study, and mortality of the HIV+ partners of HESN participants were the commonest reasons for participant study termination. Furthermore, no or low level of formal education, (AOR 2.79; 95% CI 1.29 - 6.02, p = 0.06), being unemployed (AOR 1.96; 95% CI 1.18 - 3.29, p CI 1.16 - 2.91, p Conclusion: Retention rates decline especially during month 1 (visit 1) and month 15 (visit 7) mainly due to participants’ inability to locate study participants and death of HIV+ partners of HESN enrollees. One unexpected finding from our study is that those who were more consistent in their use of condom were more likely to stay in the study. This is a possible indication of commitment or an incentive for giving free condoms at study visits. This is encouraging for combined biomedical prevention strategies where consistent condoms use is desired. On the other hand, factors such as unemployment, poor formal education and never/occasional condom use were predictors of study drop out. Retention strategies should consider these barriers and predictors of drop out as exclusion criteria in preparation for future HIV biomedical prevention trial.

Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya.

Background1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as ‘advancing research’ and collaboration with science, and personal benefits such as health benefits and financial interests.MethodA thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site.ResultsOf the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research.ConclusionThe majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine clinical trials.

Scientific challenge and advances of the HIV vaccine research

After experiencing the failures of first and second generations of HIV vaccines, the RV144 trial in Thailand, combining pox virus and gp120 vaccines, shows a 31% protection for the first time in human study. The main scientific challenge to the vaccine of a Lentivirus where HIV belongs, is the lack of protective immunity in natural infection. Therefore, novel approaches have to be developed to overcome this bottleneck in evolution. Research progresses are made in the following areas: Finding the extremely broad neutralizing antibody (bNAb) and studying their maturation mechanism from the elite controller in HIV infected people; rational design of novel HIV immunogen to trigger germline B cells activation of the bNAb; stabilizing the HIV envelope trimers and enhancing their ability to induce bNAb; using replication competent vector to strengthen the immunogenicity and durability. Only four phase IIb/III clinical trials have been conducted in the first 30 years of HIV vaccine research. More than five phase IIb/III HIV vaccine clinical trials have been planned for the next 5 years. To repeat the RV144 trial in African, NIH started the P5 project of ALVAC/gp120 vaccine started in late 2016. The Harvard and Johnson’s collaborative Ad 26/GP140 vaccine trial will be initiated in 2017/2018. To compare the replicating (rTV) and non-replication (ALVAC) pox virus vector, China CDC and NIH will conduct a joint trial of combining their DNA/rTV with gP145 vaccines in China. The two funded CHAVI-ID groups led by Duke University and the Scripps Research Institute as well as the Vaccine Research Center of NIH will push their HIV env trimer vaccine to Phase IIb trials. With the past successes in the first two lentivirus (EIAV and FIV) vaccines and the 31% human protection of RV144, HIV vaccine research will definitely contribute to the course of Ending AIDS Epidemic by 2030.

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.

Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure.

The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α–helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α–helical conformations are preferred by this segment almost universally across all subtypes. Notably, α–helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α–helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α–helical peptide epitope in the V2 loop of HIV’s surface envelope glycoprotein.

Regulatory and Ethical Approval Timelines for HIV Vaccine Studies: An Analysis of International AIDS Vaccine Initiative (IAVI) Sponsored Studies in East and Southern Africa

Background: There has not been a systematic analysis of factors affecting ethics and regulatory timelines of HIV Vaccine trials and epidemiologic studies in Eastern and Southern Africa. We analyzed regulatory and ethics approval timelines and associated factors for HIV vaccine clinical trials and epidemiologic studies in Kenya, Uganda, Rwanda, South Africa and Zambia using data collected from seven Clinical Research Centers (CRCs) from 2001 to 2015. Methodology: Staff responsible for regulatory issues at CRCs provided archived data on ethical and regulatory review time-frames which were then validated with the sponsor central database. A semi structured questionnaires was administered to establish qualitative information on perceived factors affecting efficiency of approval processes and potential solutions. Quantitative data analysis was conducted using Excel. Qualitative data were analyzed using an open coding to analyze and elicit general themes. Findings: Data on submission for 23 clinical trials and 51 epidemiological study protocols were analyzed. Across all seven CRCs it took on average of 178 and 108 days to obtain full authorization to commence clinical trials and epidemiological studies, respectively. These timelines are shorter than the average found in other disease fields in Africa but seem longer than approval timelines in the USA and the EU that are estimated at 15-45 days and 43-75 days, respectively. We found that countries with sequential, rather than parallel, submission procedures had longer review timelines. Clinical trial approval timelines that were longer than 200 days were associated with amendment submissions prior to initial approval and with investigational products that required institutional biosafety committee reviews. Lengthier approval timelines were also associated with epidemiological studies with more invasive procedures. Conclusion: Strategies to further shorten timelines will need to focus on adoption of parallel approval processes; increase frequency of ethical review meetings and capacity strengthening of ethical review institutions.

Assessment of Anti-HIV-1 Antibodies in Oral and Nasal Compartments of Volunteers From 3 Different Populations.

In this study, we assessed the feasibility of collecting standardized nasal and salivary samples at centers in Nairobi (Kenya), Kigali (Rwanda), and London (United Kingdom) using different collection devices and media (synthetic absorptive matrices versus flocked swabs, and Salimetrics oral swabs versus whole oral fluid collection). We detected anti-Gag (p24) and envelope (gp140) antibodies in both nasal fluid and salivary collections from all HIV-infected individuals, and cross-reactive anti-p24 antibodies were detected in 10% of HIV-uninfected individuals enrolled at one site. Collections from the nasal turbinates were comparable with samples collected deeper in the nasopharyngeal tract, and the yield of anti-p24 IgA in the whole oral fluid samples was higher than in samples collected from the parotid gland. We noted a trend toward reduced levels of anti-HIV antibody in the volunteers receiving anti-retroviral therapy. Levels of antibodies were stable over multiple collection visits. Overall, this study shows that nasal and salivary samples can be collected in a standardized manner over repeated visits in both low- and high-resource settings. These methods may be used in support for future HIV vaccine clinical trials.

44 Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya

44 Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya

Frontline Health Service Providers' Perspectives on HIV Vaccine Trials among Female Sex Workers and Men Who Have Sex with Men in Karnataka, South India.

BackgroundLittle qualitative research is available on the role of frontline health service providers (FHSPs) in the implementation of clinical trials, particularly in developing countries. This paper presents findings from a qualitative study about the perspectives of FHSPs on future HIV vaccine trials involving female sex workers (FSWs) and men who have sex with men (MSM) in three districts of Karnataka, India. In particular, we explore FHSPs’ knowledge of and views on clinical trials in general, and examine their potential willingness to play a role if such trials were introduced or implemented in the region.MethodsA field team of four researchers from Karnataka—two of whom self-identified with FSW or MSM communities (“community researchers”) and two with backgrounds in social work—conducted in-depth interviews with FHSPs. Including community researchers in the study helped to build rapport with FSW and MSM participants and facilitate in-depth discussions. A coding scheme for transcribed and translated data was developed using a framework analysis approach. Data was then analysed thematically using a combination of a priori and emergent codes.ResultsOver half of FHSPs demonstrated limited knowledge or understanding of clinical trials. Despite reported skepticism around the testing of HIV vaccines in developing countries and concerns around potential side effects, most FHSPs strongly advocated for the implementation of HIV vaccine clinical trials in Karnataka. Further, most FHSPs expressed their willingness to be involved in future HIV vaccine clinical trials in varying capacities.ConclusionGiven that FHSPs are often directly involved in the promotion of health and well-being of FSWs and MSM, they are well-positioned to play leadership, ethical, and communicative roles in future HIV vaccine trials. However, our findings reveal a lack of awareness of clinical trials among FHSP participants, suggesting an important area for capacity building and staff development before viable and ethical clinical trials can be set up in the region.

OMIP-027: Functional analysis of human natural killer cells.

OMIP-027: Functional analysis of human natural killer cells.

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.

Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions.

IntroductionThe development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART), would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates.DiscussionThis review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI) as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy.ConclusionsGiven the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of an ATI is not ideal.

Vectored Immunoprophylaxis Protects Humanized Mice From Mucosal HIV Transmission.

AB Balazs, Y Ouyang, CM Hong. Nat Med. 2014;20(3):296–300 A large majority of new HIV infection results from transmission across mucosal barriers. HIV vaccine clinical trials have failed to illicit protective immunity to infection. Furthermore, pre-exposure and postexposure prophylaxis regimens have had limited success, primarily due to nonadherence to the prescribed regimens. Protection with currently available vaccines to mucosal infections, such as human papilloma virus and influenza virus, correlate with systemic neutralizing antibodies. The purpose of this study was to evaluate a new strategy for prevention of HIV transmission, “vectored immunoprophylaxis,” a specific form of gene transfer therapy in which the gene for a modified broadly neutralizing antibody is directed into …

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.

A systems biology approach revealed distinct host responses between ALVAC-SIV and NYVAC-SIV vaccines during an evaluation of immunogenicity in rhesus macaques (VAC7P.992)

Abstract Though only modestly effective, RV144 is the first HIV vaccine clinical trial to show efficacy against heterosexual transmission. It tested ALVAC-HIV (a canarypox vector expressing HIV Gag, Pro and gp120) in the prime-boost combination with AIDSVAX B/E (a HIV bivalent gp120). To understand the immune correlates and inform future trials, we repeated this regimen in a rhesus model and contrasted two different pox vectors. Our study consisted of 24 animals in four groups: two initially receiving ALVAC-SIV or the vaccinia vector NYVAC-SIV (both expressing SIV Gag, Pol and Env) as the prime, with later addition of SIV gp120 and alum boosts; and two control groups receiving empty ALVAC or NYVAC and alum only. Microarray analysis of whole blood samples showed that as early as 6 hours after the initial immunization, the gene expression features of the ALVAC-SIV group were distinct from the animals receiving NYVAC-SIV, with innate immunity pathways activated in an ALVAC-SIV-specific manner. By 24 hours post vaccination, ALVAC-SIV induced more differentially expressed (DE) genes than the other three groups relative to the pre-immunization baseline, and NYVAC-SIV and NYVAC control induced similar numbers of DE genes. We will relate these very early host responses to the differences in immunogenicity observed over the course of immunization. The impact of these early events on the later outcomes will be determined once the protective efficacies of the two vaccines are determined.

HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial

RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90%. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.

Evaluation of an Intervention Among Adolescents to Reduce Preventive Misconception in HIV Vaccine Clinical Trials

Placebo and randomization are important concepts that must be understood before youth can safely participate in HIV vaccine studies or other biomedical trials for HIV prevention. These concepts are central to the phenomenon of preventive misconception that may be associated with an increase in risk behavior among study participants related to mistaken beliefs. Persuasive messaging, traditionally used in the field of marketing, could enhance educational efforts associated with randomized clinical trials. Two educational brochures were designed to increase knowledge about HIV vaccine clinical trials via one- and two-sided persuasive messaging. Through the Adolescent Medicine Trials Network, 120 youth were enrolled, administered a mock HIV vaccine trial consent, and then randomized to receive either no supplemental information or one of the two brochures. The two-sided brochure group in which common clinical trial misconceptions were acknowledged and then refuted had significantly higher scores on knowledge of randomization and interpretation of side effects than the consent-only control group, and the willingness to participate in an HIV vaccine trial was not decreased with the use of this brochure. Two-sided persuasive messaging improves understanding of the concepts of randomization and placebo among youth who would consider participating in an HIV vaccine trial. Further evaluation of this approach should be considered for at-risk youth participating in an actual trial of a biomedical intervention for HIV prevention.

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.