Interpreting HIV Serodiagnostic Test Results in the 1990s: Social Risks of HIV Vaccine Studies in Uninfected Volunteers
Robert B. BelsheM L ClementsM. C. KeeferBarney S. GrahamLawrence CoreyRichard SpostoS WescottDavid A. Lawrence
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Objective: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results. Design: Retrospective cohort study. Setting: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases. Participants: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection. Measurements: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria. Results: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected. Conclusions: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected.Keywords:
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African Americans in the United States (U.S.) are disproportionately affected by HIV. Developing an HIV vaccine is an important part of the HIV prevention and treatment toolkit and may help contribute to ending the HIV epidemic. To date, HIV vaccine trials have not engaged representative numbers of African Americans. We evaluated the willingness of African Americans to participate in HIV vaccine trials and identified correlates of willingness to participate (WTP) by surveying African Americans at low- and high-risk of HIV infection in a multi-site, cross-sectional study. We enrolled 1,452 participants; 59% heterosexual women; 21% heterosexual men; 20% men who have sex with men (MSM). Over half of participants (58%) expressed some level of WTP in HIV vaccine trials. Multivariable analyses revealed several variables were positively related to WTP: HIV risk behavior, knowing someone with HIV/AIDS, social support for trial participation, high perception of risk, perceived protection if in a trial, altruism, and greater tolerance for the ambiguous nature of trials (p<0.01). Emphasis on contextual factors related to personal HIV experiences, including knowledge of someone with HIV, and community support for research, may provide effective strategies for engaging African Americans in future HIV vaccine trials.
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Background Participation in HIV vaccine trials is an essential step towards development of an effective preventive vaccine. A Phase I/II HIV vaccine trial enrolls volunteers at low risk of acquiring HIV infection, however a few may still become infected. Understanding the experiences of volunteers who acquired HIV infection while participating in such trials is essential for future research. Here, we describe experiences of HIV infected volunteers in Phase I/II HIV vaccine trials conducted in urban Tanzania. Materials and methods We used a case study design. In-depth interviews were conducted with four participants who became HIV infected during long follow-up visits after completion of vaccination schedules in a Phase I/II trial. Between 3 and 8 years after HIV positive diagnosis, each participant was interviewed at three time points within a two-year interval so as to allow for accumulation of experiences and cross-checking the emerging constructs. Data was analyzed using a qualitative data analysis framework. Results Analysis revealed that participation in HIV vaccine trials involves balancing controversies and the spirit of informed decision. The participants declared that they did not acquire HIV from the experimental vaccine. Disclosure of HIV status within the family was gender specific. Men were hesitant to disclose their HIV status to their sexual partners fearing for the consequences. Women’s attempt to disclose their HIV status yielded negative reactions from the sexual partners. The acquired knowledge from the HIV vaccine research enabled the participants to cope with the uncertainties and their health status. Conclusions The knowledge acquired during the Phase I/II HIV vaccine trial appears to be an essential resource to cope with uncertainties post research. The HIV vaccine trial implementers need to understand the challenges the volunteers may confront after the trial while coping with their health status. Longitudinal studies are essential to trace the effects of uncertainties to the individual participants.
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HIV remains a major public health problem in Sub-Saharan Africa. About 54.5% of all people living with HIV live in Eastern and Southern Africa. There is no HIV vaccine or cure available yet despite ongoing research to develop one and uptake of vaccines is critical in the global society. It is imperative to describe the perceptions and experiences of the vaccines trial participants, as they may give lessons for COVID-19 vaccine development. A phenomenological qualitative study was conducted to describe the experiences of volunteers who participated in a phase I/II HIV vaccine trial in Tanzania. A purposive sample of 20 of the 60 trial participants was interviewed. Interviews were subjected to thematic-content analysis. The study showed that trial participation was driven by positive expectations related to health and the realization of the need for an effective vaccine to combat HIV. However, fear and concerns about the safety of the trial vaccine were the frequently reported challenges to participation. The significant others and community play an important role in trial participation. The success of a trial depends on direct and indirect participation in trials. Future vaccine trials must promote positive expectations for trial participation and address fears and concerns related to vaccine safety. Key words: HIV Vaccine trial, participant experiences, COVID-19 vaccine trial, trial benefits and challenges, Tanzania.
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Abstract Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce non-neutralizing antibodies that kill virus-infected cells as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) antibodies frequently contain potent antibody dependent cellular cytotoxicity (ADCC) making them a vaccine target. Here we explore the effect of delayed and repetitive boosting of RV144 vaccinee recipients with ALVAC/AIDSVAX B/E on the C1C2-specific antibody repertoire. It was found that boosting increased clonal lineage specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific antibody showed that it bound a highly conserved Env gp120 epitope. Thus, rationally designed boosting strategies to affinity mature these type of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than seen in the RV144 trial. Significance Over one million people become infected with HIV-1 each year making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine-regimen is the only HIV-1 clinical trial to date to demonstrate vaccine-efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine-efficacy. The RV305 HIV-1 vaccine-regimen was a follow-up boost of RV144 vaccine-recipients that occurred 6-8 years after the conclusion of RV144. Our studies focused on the effect of delayed boosting in humans on the vaccine-induced antibody repertoire. It was found that boosting with a HIV-1 Env vaccine increased antibody-mediated effector function potency and breadth.
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Our study aimed to measure the levels of serotonin and oxytocin in patients affected by end-stage renal disease (ESRD), undergoing dialysis and participating in a program of animal-assisted activities (AAAs) with a dog. Ten patients with comparable levels of ESRD were enrolled. A blood sample was taken before the start of the study in order to establish basal levels. Eleven meetings were held once a week for 3 months during the last hour of dialysis, and blood samples were collected before and after AAAs. Two more meetings, one month apart from each other, were held two months later without the dog but with the same veterinarian zootherapist. Blood was drawn at the beginning and at the end of each meeting. The samples were then processed for the measurement of serotonin and oxytocin, and data obtained were analysed using analysis of variance with mixed effect models. The results show an increasing level of both serotonin and oxytocin between subsequent meetings with the dog and an increasing trend of inter-intervention levels. Overall, the results suggest that AAAs lead to modifications of serotonin and oxytocin levels, which are also accompanied by behavioural changes of patients.
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Twenty years after its recognition, HIV / AIDS has become the most important infectious disease globally and the leading cause of death in Africa. A preventive vaccine represents the best long-term hope for its control. The development of such a vaccine, however, has encountered a number of scientific challenges, including the lack of information on immune correlates of protection, the limitations in our understanding of the relevance of primate protection experiments in relation to vaccine-induced protection in humans, and the significance of genetic and immunologic variability of HIV strains for potential vaccine efficacy. Despite these uncertainties, the first phase I trial of an HIV vaccine was conducted in the United States in 1987. Since then more than 30 candidate vaccines have been tested in over 70 phase I / II clinical trials in both industrialized and developing countries. The first HIV vaccine trial in a developing country was conducted in 1993, six years after the first trial in the United States. Since then eighteen phase I / II trials and one phase III trial have been or are being conducted in developing countries, and additional phase II and III trials are planned to start in 2003. Most of these initial trials have been conducted in Thailand, but more recently trials have been initiated in Africa, Latin America and the Caribbean. Over the past years, the HIV vaccine development effort has followed three major overlapping paradigms. The first “wave” of candidate vaccines aimed at inducing neutralizing antibodies. The second wave focused on stimulation of CD8+ T-cell responses. The current “wave” of HIV vaccine research is aimed at optimizing both humoral and cell-mediated immune responses. The first generation of candidate vaccines (based on the HIV envelope protein) entered phase III efficacy evaluation in 1998, and definitive results from these trials will become available in 2003. Plans to ensure wide access to future HIV vaccines must be developed well in advance. Keywords: hiv vaccines, aids, hiv strains, hiv envelope protein
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Most human immunodeficiency virus (HIV) vaccine trials have lacked efficacy and empirical vaccine lead targets are scarce. Thus far, the only independent correlate of reduced risk of HIV-1 acquisition in humans is elevated levels of V2-specific antibodies identified in the modestly protective RV144 vaccine trial. Ten years after RV144, human and non-human primate vaccine studies have reassessed the potential contribution of V2-specific antibodies to vaccine efficacy. In addition, studies of natural HIV-1 infection in humans have provided insight into the development of V1V2-directed antibody responses and their impact on clinical parameters and disease progression. Functionally diverse anti-V2 monoclonal antibodies were isolated and their structurally distinct V2 epitope regions characterized. After RV144, a plethora of research studies were performed using different model systems, immunogens, protocols, and challenge viruses. These diverse studies failed to provide a clear picture regarding the contribution of V2 antibodies to vaccine efficacy. Here, we summarize the biological functions and clinical findings associated with V2-specific antibodies and discuss their impact on HIV vaccine research.
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