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In March 2020, COVID-19 shuttered access to many healthcare settings offering HIV testing and there is no licensed HIV self-test in Canada.A team of nurses at the University of Ottawa and Ottawa Public Health and staff from the Ontario HIV Treatment Network (OHTN) obtained Health Canada's Special Access approval on April 23, 2020 to distribute bioLytical's INSTI HIV self-test in Ottawa; we received REB approval on May 15, 2020. As of July 20, 2020, eligible participants (≥18 years old, HIV-negative, not on PrEP, not in an HIV vaccine trial, living in Ottawa, no bleeding disorders) could register via www.GetaKit.ca to order kits.In the first 6 weeks, 637 persons completed our eligibility screener; 43.3% (n = 276) were eligible. Of eligible participants, 203 completed a baseline survey and 182 ordered a test. These 203 participants were an average of 31 years old, 72.3% were white, 60.4% were cis-male, and 55% self-identified as gay. Seventy-one percent (n = 144) belonged to a priority group for HIV testing. We have results for 70.9% (n = 129/182) of participants who ordered a kit: none were positive, 104 were negative, 22 were invalid, and 2 "preferred not to say"; 1 participant reported an unreadiness to test.Our results show that HIV self-testing is a pandemic-friendly strategy to help ensure access to sexual health services among persons who are good candidates for HIV testing. It is unsurprising that no one tested positive for HIV thus far, given the 0.08% positivity rate for HIV testing in Ottawa. As such, we advocate for scale-up of HIV self-testing in Canada.RéSUMé: CONTEXTE: En mars 2020, la COVID-19 a empêché l’accès à de nombreux établissements de santé offrant des tests de dépistage du VIH et il n’existe pas d’autotest du VIH autorisé au Canada. INTERVENTION: Une équipe d’infirmières de l’Université d’Ottawa et de Santé publique Ottawa et le personnel du Réseau ontarien de traitement du VIH (OHTN) ont obtenu l’approbation d’accès spécial de Santé Canada le 23 avril 2020 pour distribuer l’autotest VIH INSTI de bioLytical à Ottawa; nous avons reçu l’approbation du Comité d’éthique de la recherche (CER) le 15 mai 2020. À partir du 20 juillet 2020, les participants admissibles (≥18 ans, séronégatifs, ne prenant pas de PPrE, ne participant pas à un essai de vaccin contre le VIH, vivant à Ottawa, ne souffrant pas de troubles de la coagulation) pouvaient s’inscrire via www.GetaKit.ca pour commander une trousse d’autotest. RéSULTATS: Au cours des six premières semaines, 637 personnes ont rempli notre questionnaire d’admissibilité; 43,3 % (n = 276) étaient admissibles. Parmi les participants admissibles, 203 ont répondu à l’enquête de référence et 182 ont commandé un test. Ces 203 participants avaient en moyenne 31 ans, 72,3 % étaient blancs, 60,4 % étaient hommes-cis et 55 % s’identifiaient comme gays. Soixante et onze pour cent (n = 144) appartenaient à un groupe prioritaire pour le dépistage du VIH. Nous avons les résultats pour 70,9 % (n = 129/182) des participants qui ont commandé une trousse : aucun n’était positif, 104 étaient négatifs; 22 étaient invalides; 2 « préféraient ne pas le dire »; et un seul a indiqué qu’il n’était pas prêt à subir le test. CONCLUSION: Nos résultats montrent que l’autodépistage du VIH est une stratégie adaptée à la pandémie pour aider à garantir l’accès aux services de santé sexuelle aux gens qui sont de bons candidats au dépistage du VIH. Il n’est pas surprenant que personne n’ait été testé positif pour le VIH jusqu’à présent, étant donné le taux de positivité de 0,08 % pour le test de dépistage du VIH à Ottawa. C’est ce qui nous incite à préconiser l’intensification du recours à l’autotest du VIH au Canada.

Background: HIV vaccine efficacy trials require the active participation of volunteers who are committed and adherent to the study protocol. However, information about the influence of Injecting Drug Users (IDUs) to participate in HIV vaccine efficacy trials in low-income countries is inadequate. The present study explored the factors that motivate or hinder IDUs from participating in HIV vaccine efficacy trials in Dar es Salaam, Tanzania. Methods: A qualitative descriptive study design was employed among IDUs at Muhimbili National Hospital (MNH). A purposeful sampling technique was used to recruit the participants. Three (3) focus group discussions (FGDs) and 10 In-Depth Interviews (IDIs) were used to collect the data. The data from participants were audio-recorded, transcribed, and analysed using the content analysis approach. Findings: The participants reported that altruism and the desire to reduce risks of HIV infection were the motivators to participate in hypothetical HIV vaccine trials. In addition, participants reported to consult close relatives towards motivation to participate in the vaccine trial. In contrast, the perceived fear of vaccine side effects, lack of information about HIV vaccine studies, and HIV-related stigma towards participants were described as barriers to participate in the HIV vaccine trials. Conclusion: Participation in a hypothetical HIV vaccine trial among IDUs is influenced by positive and negative factors. Actual recruitment plans could be made through a better explanation of HIV vaccine trials, the expected individual and collective benefits associated with the trials. Community involvement and sensitisation is likely to enhance participation in future HIV vaccine trials in Tanzania.

Background 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. Setting 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. Methods 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. Results 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. Conclusion 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.

Background: Despite the successful conduct of three Phase I/II HIV vaccine trials in Dar es Salaam, Tanzania, misperception around the trials has been reported. In this study, misperception means incorrect understanding that in Phase I/II HIV vaccine trial, the researchers infected the volunteers with HIV. We describe the magnitude of misperception around HIV vaccine trials and associated factors among participating communities in Dar es Salaam, Tanzania. Methods: We conducted a cross-sectional study that included 605 respondents aged ³18 years from the communities that participated in Phase I/II HIV vaccine trials. These communities comprised of youths, Police and Prison officers. Respondents were interviewed using a pre-tested questionnaire on socio-demographic characteristics, HIV knowledge, and responses to HIV vaccine trial related questions. Results: Of the 605 respondents, 156 (26%) had misperception that the researchers infected the volunteers with HIV during the trials, while 58% weren’t sure whether the researchers infected the volunteers with the HIV or not. Awareness about progress in HIV vaccine development (adjusted risk ratio (RR)=1.50; 95% CI=1.11 – 2.04), participation in an HIV vaccine sensitization meeting (adjusted RR=1.50; 95% CI=1.14-1.97) and advanced secondary education (adjusted RR=1.92; 95% CI=1.19 – 3.09) were associated with an increased likelihood of having the misperception that researchers infected the volunteers. Nevertheless, the majority (94.5%) of respondents showed a willingness to know more about ongoing HIV vaccine studies while about 44.3% had reservations of taking part in HIV vaccine trials due to fear of getting HIV from the vaccine. Conclusions: The misperception that researchers infected volunteers with HIV in Phase I/II trial is significant and was associated with respondents’ awareness about HIV vaccine development, participation in sensitization meetings and advanced education. Partial knowledge about HIV vaccine trials was of note. Future HIV vaccine trials should strive to address the knowledge gap.

Fishing communities are a new “Most at Risk Population for HIV in sub-Saharan Africa

In HIV vaccine studies, longitudinal immune response biomarker data are often left-censored due to lower limits of quantification of the employed immunological assays. The censoring information is important for predicting HIV infection, the failure event of interest. We propose two approaches to addressing left censoring in longitudinal data: one that makes no distributional assumptions for the censored data – treating left censored values as a “point mass” subgroup – and the other makes a distributional assumption for a subset of the censored data but not for the remaining subset. We develop these two approaches to handling censoring for joint modelling of longitudinal and survival data via a Cox proportional hazards model fit by h-likelihood. We evaluate the new methods via simulation and analyze an HIV vaccine trial data set, finding that longitudinal characteristics of the immune response biomarkers are highly associated with the risk of HIV infection.

Background: Vaccinia based immunizations have caused myo/pericarditis and vaccine study volunteers are monitored by ECG. We report ECG outcome obtained during the screening period for an HIV vaccine trial. Methods: ECG was performed in healthy Tanzanian volunteers. ECG abnormalities and findings interfering with the interpretation of myo/pericarditis were subject to study ineligibility. We determined the prevalence of left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon (SL) or the Cornell index, ST-elevations and early repolarization (ERP) in association with gender, age, BMI and body height by regression analysis adjusted for gender and age. Results: In 257 volunteers (median age 23 years, 63% males) overall positivity for LVH defined by SL or Cornell criteria was seen in 20.6% and 3.5%, ST-elevations ≥0.1 mV or ≥0.2 mV in 77.8% and 38.1%, and ERP in 23.4%. Positive SL criteria were associated with male gender (PR 7.84, p

Despite advances in preventive treatments for HIV, children continue to become infected with HIV. Research has investigated adult and adolescents’ willingness to participate in hypothetical HIV vaccine trials; however, maternal willingness to enroll their infants in such trials remains underexplored. Aim: This study explored the factors influencing mothers’ decision-making about enrolling their HIV negative infants in a hypothetical HIV vaccine trial. Methods: HIV infected and uninfected mothers (n = 22) were interviewed. Results: Several factors were identified as influencing the mothers’ decisions, including perceptions and knowledge of HIV and vaccines. Conclusion: Maternal concerns about protecting their infants from HIV were also identified and mothers indicated that they were eager to vaccinate their children. Insufficient information and reassurance regarding vaccine trial safety and efficacy influenced maternal reluctance to enroll their child.

Defining and identifying causal intervention effects for transmissible infectious disease outcomes is challenging because a treatment – such as a vaccine – given to one individual may affect the infection outcomes of others. Epidemiologists have proposed causal estimands to quantify effects of interventions under contagion using a two-person partnership model. These simple conceptual models have helped researchers develop causal estimands relevant to clinical evaluation of vaccine effects. However, many of these partnership models are formulated under structural assumptions that preclude realistic infectious disease transmission dynamics, limiting their conceptual usefulness in defining and identifying causal treatment effects in empirical intervention trials. In this paper, we propose causal intervention effects in two-person partnerships under arbitrary infectious disease transmission dynamics, and give nonparametric identification results showing how effects can be estimated in empirical trials using time-to-infection or binary outcome data. The key insight is that contagion is a causal phenomenon that induces conditional independencies on infection outcomes that can be exploited for the identification of clinically meaningful causal estimands. These new estimands are compared to existing quantities, and results are illustrated using a realistic simulation of an HIV vaccine trial.

Purpose of Review The design of an HIV vaccine remains an elusive but top priority. Data from the non-human primate model and the first moderately protective HIV vaccine trial (RV144) point to a role for qualitative changes in humoral immune functions in protection from infection. Here, we review the current understanding of the antibody response throughout HIV infection, the known correlates of protection, and current strategies to manipulate antibodies to put an end to the epidemic. Recent Findings Recent studies point to innate immune-recruiting antibody function in preventing infection as well as controlling viremia following infection. These data have begun to inform next-generation design of HIV vaccines and antibody therapies by uncovering new viral targets and antibody architectures to improve potency and breadth. Summary Emerging data illustrate a role for innate immune recruiting-antibodies in conferring protection against HIV infection as well as promoting viral control and clearance, offering an unprecedented opportunity to modulate and improve antibody function to fight HIV more effectively.

Background The search for an efficacious HIV vaccine is a global priority. To date only one HIV vaccine trial (RV144) has shown modest efficacy in a phase III trial. With existing different HIV-1 subtypes and frequent mutations, multiple trials are needed from different geographical sites particularly in sub-Saharan Africa where most HIV infections occur. Thus, motivations to participate in HIV vaccine trials among Tanzanians need to be assessed. This paper describes the motives of Police Officers who showed great interest to volunteer in HIVIS-03 in Dar es Salaam, Tanzania. Methods A descriptive cross-sectional study was conducted among Police Officers who showed interest to participate in the HIVIS-03, a phase I/II HIV vaccine trial in Dar es Salaam. Prior to detailed training sessions about HIV vaccine trials, the potential participants narrated their individual motives to participate in the trial on a piece of paper. Descriptive analysis using content approach and frequency distributions were performed. Results Of the 265 respondents, 242 (91.3 %) provided their socio-demographic characteristics as well as reasons that would make them take part in the proposed trial. Majority, (39.7 %), cited altruism as the main motive. Women were more likely to volunteer due to altruism compared to men (P

Summary: Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called ‘sieve analysis’, one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Availability and Implementation: Visualization: http://sieve.fredhutch.org/viz. Source code: https://github.com/nkullman/SIEVE. Data API: http://sieve.fredhutch.org/data. Contact: agartlan@fredhutch.org

HIV-1 infection continues to be a global health challenge and a vaccine is urgently needed. Broadly neutralizing antibodies (bNAbs) are considered essential as they inhibit multiple HIV-1 strains, but they are difficult to elicit by conventional immunization. In contrast, non-neutralizing antibodies that correlated with reduced risk of infection in the RV144 HIV vaccine trial are relatively easy to induce, but responses are not durable. To overcome these obstacles, adeno-associated virus (AAV) vectors were used to provide long-term expression of antibodies targeting the V2 region of the HIV-1 envelope protein, including the potent CAP256-VRC26.25 bNAb, as well as non-neutralizing CAP228 antibodies that resemble those elicited by vaccination. AAVs mediated effective antibody expression in cell culture and immunocompetent mice. Mean concentrations of human immunoglobulin G (IgG) in mouse sera increased rapidly following a single AAV injection, reaching 8–60 μg/mL for CAP256 antibodies and 44–220 μg/mL for CAP228 antibodies over 24 weeks, but antibody concentrations varied for individual mice. Secreted antibodies collected from serum retained the expected binding and neutralizing activity. The vectors generated here are, therefore, suitable for the delivery of V2-targeting HIV antibodies, and they could be used in a vectored immunoprophylaxis (VIP) approach to sustain the level of antibody expression required to prevent HIV infection.

HIV prevention trials provide a prevention package to participants to help prevent HIV acquisition. As new prevention methods are proven effective, this raises ethical and scientific design complexities regarding the prevention package or standard of prevention. Given its high HIV incidence and prevalence, South Africa has become a hub for HIV prevention research. For this reason, it is critical to study the implementation of relevant ethical-legal frameworks for such research in South Africa. This qualitative study used in-depth interviews to explore the practices and perspectives of eight members of South African research ethics committees (RECs) who have reviewed protocols for HIV vaccine trials. Their practices and perspectives are compared with ethics guideline requirements for standards of prevention.

Background For more than three decades, Human Immunodeficiency Virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS) continue to dominate the health agenda. In sub-Saharan African countries, women are at more risk of contracting HIV and AIDS compared with men due to biological, social, economic, socio-economic and cultural factors. Women in the uniformed services may be more vulnerable to HIV/AIDS because of their work context, mobility, age and other factors that expose them to a higher risk of infection than women in the general population. This article describes gender dimensions, motives and challenges towards HIV prevention amongst Police officers (POs) in Dar es Salaam, Tanzania. Methods This was a descriptive qualitative study conducted at Police stations in Dar es Salaam, Tanzania. Fifteen in-depth interviews were conducted on POs; seven men, and eight women. Content analysis approach was used to analyze data. Results Participants’ self-descriptions shed light on gender differences in relation to self -perceptions, job contexts, sexual relationships and HIV prevention. Both men and women perceived themselves as role models, and believed that the surrounding community perceived the same. Safe sexual behavior appeared crucial to avoid undesirable health outcomes. Risky sexual practices were considered avoidable. Under unavoidable sexual temptations, women in particular would be keen to avoid risky sexual practices. Some participants expressed positive views towards condoms use during extra-marital sexual relationships, while others had negative opinions. Early phases of HIV vaccine trials appeared to gain support from sexual partners. However, condom use during phase I/II HIV vaccine trials was deemed as difficult. Support from the spouse was reported to influence condom use outside the wedlock. However, religious beliefs, socio-cultural issues and individual reasons were perceived as difficulties to promote condoms use. Conclusions These findings increase understanding of gender differences and context specific efforts towards HIV prevention. Individuals’ assertiveness against risky sexual practices and the intention to participate in HIV vaccine trials to develop an effective vaccine are worth noting. Nevertheless, uncertainties towards condoms use underscore the importance of condoms’ marketing particularly in extra marital sexual relationships and during early HIV vaccine trials.

An examination of age and sex or gender (sex/gender) in HIV vaccine preparedness studies can contribute to an understanding of these demographic variables in preparation for actual HIV vaccine trials. In this descriptive review, age and sex or gender (sex/gender) were examined in relation to willingness to participate (WTP) and retention in an HIV vaccine trial. Twenty-five articles were retrieved from the Organization for Economic Co-operation and Development (OECD) countries and 28 articles were retrieved from the non-OECD countries. In US studies that involved mainly white MSM, older men were more likely to be WTP in a hypothetical HIV vaccine trial and more likely to be retained than younger men. In most OECD studies, sex/gender was not associated with WTP in a hypothetical HIV vaccine trial, while females were more likely to be retained in most studies. Largely, age was not associated with WTP in the non-OECD countries, but the results on sex/gender were more variable. The relationship between adolescent or adult WTP in hypothetical HIV vaccine trials in South Africa did not appear to be modified by high school student status. In addition, more studies in discordant couples in the context of HIV vaccine preparedness could be conducted to examine gender roles and inequalities in preparation for HIV vaccine trials.

Introduction AIDS vaccine is seen as the ultimate prevention tool that will complement the existing prevention strategies in place. Patients participate in HIV vaccine trials with hope that developing a safe and effective AIDS vaccine is possible. To begin to understand adolescent attitudes to these complex issues, and inform our future work with adolescents in HIV vaccine trials, we undertook a formative study examining attitudes towards such trials, potential motivating factors and hypothetical willingness to participate, among youth. Methods A self-administered, facilitated questionnaire was administered to 277 students in pre university colleges, Mangalore, India from August 2012 to February 2013. The questionnaire explored general HIV knowledge, perception of adolescent risk, knowledge of vaccine concepts, willingness to participate in future vaccine trials, perceived personal and social harms and benefits associated with participation as well as barriers and facilitators to participating in future HIV vaccine trials. Results 277 college-going youth provided consent to participate, and if under 18, we also obtained written consent from a parent. Of the 241 participants who responded to the question on HIV testing, 10% indicated that they have tested for HIV. Of the majority (57%) of participants believed that parents should give permission for their child’s HIV test while most of the participants (84%) believed that parents should know the HIV status of their child. Conclusion The youth report high degrees of willingness to participate in HIV vaccine trials. This may be related to the high levels of adolescent HIV risk perception. The spectre of HIV infection looms regardless of age group, and adolescents are no exception. Indeed, public health practice would seem to say that effective vaccination of this subgroup above all would result in the greatest reduction in new infections.

Introduction An estimated 36.7 million people live with HIV/AIDS in 2015, with more than 3 million people living with the virus in Nigeria, ranking the country among the top three most affected. Because adults are mostly affected by this epidemic, their inclusion in HIV vaccine trials is of utmost importance in obtaining an effective and acceptable vaccine. This study objectives were to determine the proportion of adults willing-to-participate (WTP) in early HIV vaccine trial, evaluate the factors determining their participation as well as their entire knowledge and perception about HIV vaccine trials. Hypotheses tested included association between WTP and age, gender and knowledge about the vaccine. Methods Data was obtained from 3500 young persons (15–49 years) recruited by a multi-stage sample technique between September 2015 and September 2016. The cross-sectional study was carried out using a face-to-face interview by trained volunteers and supervised by appointed supervisors and investigators. An informed consent was obtained through a pre-tested structured questionnaire, with questions addressing socio-demographics, HIV vaccine studies knowledge and perception, sexual behaviour and possible stigma from HIV vaccine trial participation. Ethical approval was obtained from the Ethics and Research Committee of the Federal Teaching Hospital, Ido Ekiti, Nigeria. Data was analysed using SPSS software, with significance fixed at p Results The mean age ± SD was 27.53±3.46 years. 1094 (31.3%) expressed their willingness to definitely participate in the vaccine studies while 999 (28.5%) reported that they may participate especially if a very tangible incentive will be given. Unwillingness to participate was associated with safety concerns (12.0), side effects (5.0%), fear of HIV infection from vaccine (4.1%), time required for study (1.9%) and partner’s sexual intercourse refusal (1.2%). 983 (28.3%) reported people in good health, HIV negative individuals and at low risk of HIV infection, are eligible for HIV vaccine trial. There was a significant association between willing to participate in HIV vaccine trials as well as age and gender. Conclusion Participation in an HIV vaccine trial in a Nigerian context is likely to be influenced by comprehensive education about the vaccine trial concept, addressing issues relating to concerns and possible risks pertaining to participation as well as incentives, as the WTP in the vaccine trial is quite low probably due to the participants’ perception and inadequate knowledge as evidenced in this research.

Introduction AIDS vaccine research is complex; the role of an AIDS vaccine advocate is challenging. Explaining the hopeful, yet slow and complicated progress in AIDS vaccine research to non-scientific stakeholders requires someone with relatively deep knowledge of complex science, research process, and related technical issues. Likewise, the critical role of representing stakeholder concerns to AIDS vaccine researchers requires someone who can speak in language that commands scientist’s attention and respect. Methods Through the Vaccine Advocacy Resource Group (VARG) a global team of AIDS prevention research advocates play a critical liaison role in a highly complex scientific field. Since 2014, the VARG has been convened virtually largely through teleconferences and email to receive research updates, discuss advocates perspectives and priorities, and to move forward key actions. Since 2015 this engagement has increasingly happened in person at some of the worlds largest HIV Vaccine Trial gatherings, elevating the role of community based advocates in a traditionally scientific space. Results These efforts have been impactful in terms of coalescing the team of vaccine-specific advocates, building VARG members skills and understanding to a certain degree, and preparing them for conferences and scientific meetings. Conclusion This poster aims to demonstrate how building the capacity of community advocates on the science of HIV Prevention Research Advocacy, particularly how it relates to vaccine research can strengthen community ownership of clinical trials and result in AIDS competent communities long before the trial has ended, as that community continues to advocate for increased awareness of, access to and uptake of existing HIV and STI prevention options

Despite a trend of declining HIV incidence rates, up to 2 million people continue to become newly infected with HIV every year. Antiretroviral-based interventions offer optimism to achieve epidemic control, but a vaccine is needed to eliminate HIV. The path to a vaccine remains elusive because of unique features of the virus, including its ability to attack vital parts of the immune system, its high mutation rate and a little understanding on what protects a human, due to a lack of examples of a natural cure. This chapter reviews CAPRISA’s contribution to HIV vaccine research over the past decade focusing on CAPRISA’s involvement in the National Institute of Health-funded HIV Vaccine Trial Network (HVTN) Phambili trial, the first phase IIb HIV vaccine study conducted in sub-Saharan Africa, and lessons learnt during its premature closure. We then discuss ongoing Vanguard vaccine studies in preparation for the next generation of efficacy trials that CAPRISA is participating in sponsored by HVTN and Janssen Pharmaceuticals. We conclude with a synopsis of CAPRISA’s contributions to passive immunisation studies for HIV prevention.

To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p = 0.004) and 52% against viruses matching the vaccine at V3 site 307 (p = 0.004). This analysis was supported by data showing that vaccinees' plasma Abs were less reactive with I307 when replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317 were less infectious, possibly due to the contribution of F317 to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine., Highlights • The RV144 vaccine reduced infection by viruses with isoleucine in V3 position 307. • Many vaccine-induced antibodies are cross-reactive and target an epitope including I307. • There was selection for breakthrough viruses carrying F317 in V3 (p = 0.004). • F317 is needed to maintain optimal infectivity. • F317 is a poor or non-contact residue for vaccine induced V3 antibodies.

Men who sleep with men (MSM) and transgender individuals of color, the largest demographic in the House Ball community (HBC) are amongst the group at highest risk for HIV infection in the United States. The HBC have limited access to culturally appropriate HIV education. This study aimed to develop a partnership with HBC leaders to uncover strategies for increasing HIV prevention knowledge, including participation in HIV vaccine trials. To this end a research institution-community-HBC partnership was established. In-depth qualitative and quantitative data were collected from the 14 HBC leaders in western New York, revealing that knowledge of HIV and related vaccine trials was limited. Barriers to increasing HIV knowledge included fear of peer judgment, having inaccurate information about HIV, and lack of education. Among the HBC, community partnerships will further aid in the development of future HIV prevention programs and increase individuals’ willingness to participate in future HIV vaccine trials.

Introduction Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. Methods In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. Results In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Conclusion Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

BackgroundThere remains an urgent need for a prophylactic HIV vaccine to control generalised epidemics. PrEP has demonstrated effectiveness of 86% and is recommended by WHO; uptake is generally high, but retention is disappointing in some settings. The EDCTP2 project PrEPVacc will assess the efficacy of two combination prophylactic vaccine regimens (DNA, MVA and Env protein/adjuvant) each compared to placebo and the proportion of infections averted by F/TAF in comparison to TDF/FTC. A Registration Cohort, recruiting HIV negative volunteers at risk of HIV will precede the trial.MethodsThe PrEPVacc partnership agreed that 70% vaccine efficacy had public health relevance. The trial uses nstage software for multi-arm, multi-stage designs (MAMS) and the averted infections ratio (AIR) methodology with participants randomised (i) 1:1:1 to active product or placebo (ii) 1:1 to TDF/FTC : F/TAF until week 26 (presumed peak immunogenicity). Access to PrEP in the Registration Cohort and after week 26 will be standard of care. HIV seroconversions occurring between weeks 0–26 will inform the PrEP analysis, incorporating HIV incidence amongst those who do not take up PrEP locally in the Registration Cohort. Seroconversions after week 26 will inform vaccine analyses.ResultsUp to 556 participants per group affords 92% power to detect vaccine efficacy of 70% at the final analysis, assuming incidence of 4/100-person years and 10% loss with 81% and 97% power to conclude that F/TAF can avert half or more of the infections prevented by TDF/FTC if effectiveness of TDF/FTC is 70% and 80%, respectively.ConclusionPrEPVacc adopts a pragmatic approach to uncertainties around HIV incidence in settings where PrEP is increasingly available. This innovative adaptive trial design uses validated software to determine vaccine efficacy and a novel methodology to evaluate a new PrEP agent, overcoming the challenge of demonstrating non-inferiority when adherence to TDF/FTC is high and the number of outcome events very low.

In vaccine research, immune biomarkers that can reliably predict a vaccine's effect on the clinical endpoint (i.e., surrogate markers) are important tools for guiding vaccine development. This article addresses issues on optimizing two-phase sampling study design for evaluating surrogate markers in a principal surrogate framework, motivated by the design of a future HIV vaccine trial. To address the problem of missing potential outcomes in a standard trial design, novel trial designs have been proposed that utilize baseline predictors of the immune response biomarker(s) and/or augment the trial by vaccinating uninfected placebo recipients at the end of the trial and measuring their immune biomarkers. However, inefficient use of the augmented information can lead to counter-intuitive results on the precision of estimation. To remedy this problem, we propose a pseudo-score type estimator suitable for the augmented design and characterize its asymptotic properties. This estimator has superior performance compared with existing estimators and allows calculation of analytical variances useful for guiding study design. Based on the new estimator we investigate in detail the problem of optimizing the sampling scheme of a biomarker in a vaccine efficacy trial for efficiently estimating its surrogate effect, as characterized by the vaccine efficacy curve (a causal effect predictiveness curve) and by the predicted overall vaccine efficacy using the biomarker.

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%).