Human Immunodeficiency Virus Vaccine Trials Research Articles

Comprehension of informed consent and voluntary participation in registration cohorts for phase IIb HIV vaccine trial in Dar Es Salaam, Tanzania: a qualitative descriptive study

BackgroundInformed consent as stipulated in regulatory human research guidelines requires volunteers to be well-informed about what will happen to them in a trial. However, researchers may be faced with the challenge of how to ensure that a volunteer agreeing to take part in a clinical trial is truly informed. This study aimed to find out volunteers’ comprehension of informed consent and voluntary participation in Human Immunodeficiency Virus (HIV) clinical trials during the registration cohort.MethodsWe conducted a qualitative study among volunteers who were enrolled in the registration cohort of HIV clinical trials in Dar es Salaam, Tanzania. A purposive sampling strategy was used to obtain twenty study participants. The data were collected between June and September 2020 using a semi-structured interview guide. In-depth interviews were used to collect the data to obtain deep insights of the individual study participants on the comprehension of informed consent and participation in the clinical trial. A thematic analysis approach was used to analyze the data. Themes and subthemes were supported by the quotes from the participants.ResultsVolunteers described comprehension of informed consent from different perspectives. They reported that various components of the informed consent such as study procedure, confidentiality, risk and benefits were grasped during engagement meetings. Furthermore, the volunteers’ decision to participate in the registration cohort was voluntary. However, trial aspects such as health insurance, free condoms, and medical checkups could have indirectly influenced their reluctance to withdraw from the study.ConclusionEngagement meetings may increase the comprehension of informed consent among potential participants for HIV clinical trials. However, trial incentives may influence participation, and thus future research should focus on the challenges of giving incentives in the study. This will ensure comprehension and voluntary participation in the context of HIV clinical trials.

Major HIV vaccine candidates

Introduction and objective: Human immunodeficiency virus (HIV) is a virus, which is responsible for an acquired immunodeficiency syndrome (AIDS). This pathogen is widespread worldwide causing a pandemic that has been going on for decades. Researches around the world are trying to end this situation and it seems that the greatest hope lies in finding an effective vaccine. It is important due to the fact that AIDS and its consequences are responsible even nowadays for death of many people infected around the world. The aim of this study was to provide the most important information about major HIV vaccine trials and efficacy of vaccine candidates.
 Materials and methods: For the purposes of writing this article, the available literature was reviewed. The database of medical publications – Pubmed datebase and other publicaly available books, database and online sites was searched, with the use of keywords such as HIV, HIV vaccine, HIV epidemiology.
 State of knowledge: According to review studies HIV vaccine trials has been going for 4 decades. Over 250 trials has been conducted since then, but unfortunately, none of them resulted in effective vaccine. The difficulties of this task are mainly connected with the nature of HIV virus. To date, one study has shown some effectiveness, but not enough to claim success. Other studies are ongoing around the world and more are planned.
 Conclusions: Developing an effective HIV vaccine is the clue to solving the problem, which is new HIV infections. Further researches, further research funding and international cooperation are needed to end this pandemic.

Causal Isotonic Regression.

In observational studies, potential confounders may distort the causal relationship between an exposure and an outcome. However, under some conditions, a causal dose-response curve can be recovered using the G-computation formula. Most classical methods for estimating such curves when the exposure is continuous rely on restrictive parametric assumptions, which carry significant risk of model misspecification. Nonparametric estimation in this context is challenging because in a nonparametric model these curves cannot be estimated at regular rates. Many available nonparametric estimators are sensitive to the selection of certain tuning parameters, and performing valid inference with such estimators can be difficult. In this work, we propose a nonparametric estimator of a causal dose-response curve known to be monotone. We show that our proposed estimation procedure generalizes the classical least-squares isotonic regression estimator of a monotone regression function. Specifically, it does not involve tuning parameters, and is invariant to strictly monotone transformations of the exposure variable. We describe theoretical properties of our proposed estimator, including its irregular limit distribution and the potential for doubly-robust inference. Furthermore, we illustrate its performance via numerical studies, and use it to assess the relationship between BMI and immune response in HIV vaccine trials.

Young men who have sex with men’s awareness, acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study

BackgroundNew cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM’s vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research. MethodsThis secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI.We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses. ResultsAcceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (β = 0.62) and 85% (β = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (β = −0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (β = 0.18) and altruism (β = 0.60), and negatively associated with education (β = −0.21). ConclusionsYMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns.ClinicalTrials.gov Identifier: NCT02842060.

Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody.

Studies demonstrate a protective effect of antibodies (Abs) in breast milk (BM) against mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Contribution of the BM cellular component has been overlooked. The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with Abs mediating functions through the constant immunoglobulin region-the crystallizable fragment (Fc). These data support induction of vaccine Abs triggering antiviral activities by leukocytes through Fc receptors (FcRs). To measure Ab-dependent cellular phagocytosis (ADCP), an essential Fc-mediated response, by BM phagocytes. Cells were isolated from five human BM samples obtained at 7-183 days postpartum and analyzed for ADCP. Fluorescent beads coated with HIV envelope (Env) epitopes were used as targets. Sixty-seven to 100 mL of milk was utilized. Total cell concentrations per milliliter were 16,083-222,857, with 1.6-12.3% being CD45+ leukocytes. ADCP activity was measurable using the HIV-specific Ab 830A. Use of the actin inhibitor cytochalasin D and FcR blocker indicated that ADCP was actin dependent and required FcR engagement. ADCP scores were variable, but largely consistent, across the samples studied, exhibiting <4-fold difference from lowest to highest activity for CD45+ cells. Of the CD45+ ADCP, significantly more activity was granulocyte derived (72-95%), while the remaining activity was monocyte driven. The data indicate that BM phagocytes can manifest antiviral activities in the presence of specific Abs and therefore may contribute to reduction of MTCT of HIV.

Gender aspects on HIV prevention efforts and participation in HIV vaccine trials among Police officers in Dar es Salaam, Tanzania

BackgroundFor 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.MethodsThis 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.ResultsParticipants’ 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.ConclusionsThese 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.

Sparse partial least squares with group and subgroup structure.

Integrative analysis of high dimensional omics datasets has been studied by many authors in recent years. By incorporating prior known relationships among the variables, these analyses have been successful in elucidating the relationships between different sets of omics data. In this article, our goal is to identify important relationships between genomic expression and cytokine data from a human immunodeficiency virus vaccine trial. We proposed a flexible partial least squares technique, which incorporates group and subgroup structure in the modelling process. Our new method accounts for both grouping of genetic markers (eg, gene sets) and temporal effects. The method generalises existing sparse modelling techniques in the partial least squares methodology and establishes theoretical connections to variable selection methods for supervised and unsupervised problems. Simulation studies are performed to investigate the performance of our methods over alternative sparse approaches. Our R package sgspls is available at https://github.com/matt-sutton/sgspls.

Capturing public interest toward new tools for controlling human immunodeficiency virus (HIV) infection exploiting data from Google Trends.

Human immunodeficiency virus vaccination and pre-exposure prophylaxis represent two different emerging preventive tools. Google Trends was used to assess the public interest toward these tools in terms of digital activities. Worldwide web searches concerning the human immunodeficiency virus vaccine represented 0.34 percent, 0.03 percent, and 46.97 percent of human immunodeficiency virus, acquired immune deficiency syndrome, and human immunodeficiency virus/acquired immune deficiency syndrome treatment-related Google Trends queries, respectively. Concerning temporal trends, digital activities were shown to increase from 0 percent as of 1 January 2004 percent to 46 percent as of 8 October 2017 with two spikes observed in May and July 2012, coinciding with the US Food and Drug Administration approval. Bursts in search number and volume were recorded as human immunodeficiency virus vaccine trials emerged. This search topic has decreased in the past decade in parallel to the increase in Truvada-related topics. Concentrated searches were noticed among African countries with high human immunodeficiency virus/acquired immune deficiency syndrome prevalence. Stakeholders should take advantage of public interest especially in preventive medicine in high disease burden countries.

Using Digital Technologies in Clinical HIV Research: Real-World Applications and Considerations for Future Work

BackgroundDigital technologies, especially if used in novel ways, provide a number of potential advantages to clinical research in trials related to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) and may greatly facilitate operations as well as data collection and analysis. These technologies may even allow answering questions that are not answerable with older technologies. However, they come with a variety of potential concerns for both the participants and the trial sponsors. The exact challenges and means for alleviation depend on the technology and on the population in which it is deployed, and the rapidly changing landscape of digital technologies presents a challenge for creating future-proof guidelines for technology application.ObjectiveThe aim of this study was to identify and summarize some common themes that are frequently encountered by researchers in this context and highlight those that should be carefully considered before making a decision to include these technologies in their research.MethodsIn April 2016, the Global HIV Vaccine Enterprise surveyed the field for research groups with recent experience in novel applications of digital technologies in HIV clinical research and convened these groups for a 1-day meeting. Real-world uses of various technologies were presented and discussed by 46 attendees, most of whom were researchers involved in the design and conduct of clinical trials of biomedical HIV prevention and treatment approaches. After the meeting, a small group of organizers reviewed the presentations and feedback obtained during the meeting and categorized various lessons-learned to identify common themes. A group of 9 experts developed a draft summary of the findings that was circulated via email to all 46 attendees for review. Taking into account the feedback received, the group finalized the considerations that are presented here.ResultsMeeting presenters and attendees discussed the many successful applications of digital technologies to improve research outcomes, such as those for recruitment and enrollment, participant identification, informed consent, data collection, data quality, and protocol or treatment adherence. These discussions also revealed unintended consequence of technology usage, including risks to study participants and risks to study integrity.ConclusionsKey lessons learned from these discussions included the need to thoroughly evaluate systems to be used, the idea that early success may not be sustained throughout the study, that some failures will occur, and considerations for study-provided devices. Additionally, taking these key lessons into account, the group generated recommendations on how to move forward with the use of technology in HIV vaccine and biomedical prevention trials.

A Phase 1 Human Immunodeficiency Virus Vaccine Trial for Cross-Profiling the Kinetics of Serum and Mucosal Antibody Responses to CN54gp140 Modulated by Two Homologous Prime-Boost Vaccine Regimens.

A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months. The two homologous prime-boost regimens were well tolerated and induced CN54gp140-specific responses that were observed in both the systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with FcγR engagement, and both vaccine regimens were associated with strikingly similar patterns in antibody titer and FcγR-binding profiles. In both groups, identical changes in the antigen (Ag)-specific IgG-subclass fingerprint, leading to a decrease in IgG1 and an increase in IgG4 levels, were modulated by booster injections. Here, the dissection of immune profiles further supports the notion that prime-boost strategies are essential for the induction of diverse Ag-specific HIV-1 responses. The results reported here clearly demonstrate that identical responses were effectively and safely induced by both vaccine regimens, indicating that an accelerated 6-month regimen could be employed for the rapid induction of immune responses against CN54gp140 with no apparent impact on the overall quality of the induced immune response. (This study has been registered at http://ClinicalTrials.gov under registration no. NCT01966900.)

Combining biomarkers for classification with covariate adjustment.

Combining multiple markers can improve classification accuracy compared with using a single marker. In practice, covariates associated with markers or disease outcome can affect the performance of a biomarker or biomarker combination in the population. The covariate-adjusted receiver operating characteristic (ROC) curve has been proposed as a tool to tease out the covariate effect in the evaluation of a single marker; this curve characterizes the classification accuracy solely because of the marker of interest. However, research on the effect of covariates on the performance of marker combinations and on how to adjust for the covariate effect when combining markers is still lacking. In this article, we examine the effect of covariates on classification performance of linear marker combinations and propose to adjust for covariates in combining markers by maximizing the nonparametric estimate of the area under the covariate-adjusted ROC curve. The proposed method provides a way to estimate the best linear biomarker combination that is robust to risk model assumptions underlying alternative regression-model-based methods. The proposed estimator is shown to be consistent and asymptotically normally distributed. We conduct simulations to evaluate the performance of our estimator in cohort and case/control designs and compare several different weighting strategies during estimation with respect to efficiency. Our estimator is also compared with alternative regression-model-based estimators or estimators that maximize the empirical area under the ROC curve, with respect to bias and efficiency. We apply the proposed method to a biomarker study from an human immunodeficiency virus vaccine trial. Copyright © 2017 John Wiley & Sons, Ltd.

Higher T-Cell Responses Induced by DNA/rAd5 HIV-1 Preventive Vaccine Are Associated With Lower HIV-1 Infection Risk in an Efficacy Trial.

It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial. 2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4+ T-cell magnitude and Env-specific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection. We observed an unexpectedly strong inverse correlation between Env-specific CD8+ immune response magnitude and HIV-1 infection risk (hazard ratio [HR] = 0.18 per SD increment; P = .04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01). Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection.

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

An update on human immunodeficiency virus vaccine preparedness studies.

Human immunodeficiency virus (HIV) vaccine preparedness studies (VPSs) have taken place in both the Organisation for Economic Co-operation and Development (OECD) countries and the non-OECD countries. HIV VPSs are conducted to assess the feasibility of phase 3 HIV vaccine trials. This descriptive review is an update of HIV VPSs in the non-OECD countries, and examines the willingness to participate (WTP) in hypothetical HIV vaccine trials, as well as retention. Few VPSs have been published in the OECD countries since the discontinuation of the STEP/Phambili HIV vaccine trials. Barriers to participation in the non-OECD countries after the STEP/Phambili studies include safety issues and side effects, vaccine-induced seropositivity (VISP) and mistrust among key informants (KIs). HIV VPSs indicate that HIV vaccine trials are still feasible in the non-OECD countries, but barriers must be overcome to improve feasibility. Hypothetical WTP in a VPS may not translate into actual WTP in an HIV vaccine trial.

Strategies for preventing mucosal cell-associated HIV transmission.

Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission.

HIV vaccine trial exploits a dual and central role for innate immunity.

Limited understanding of correlates of protection from HIV transmission hinders development of an efficacious vaccine. D. J. M. Lewis and colleagues (J. Virol. 88:11648-11657, 2014, doi:10.1128/JVI.01621-14) now report that vaginal immunization with an HIVgp140 vaccine linked to the 70-kDa heat shock protein downregulated the human immunodeficiency virus (HIV) coreceptor CCR5 (chemokine [C-C motif] receptor 5) and increased expression of the HIV resistance factor APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G), in women. These effects correlated with HIV suppression ex vivo. Thus, vaccine-induced innate responses not only facilitate adaptive immunity-they may prove to be critical for preventing HIV transmission.

Clade B virus-like particle (VLP)-expressing HIV vaccine

A human immunodeficiency virus (HIV) vaccine is of high importance for the control of the current pandemic. Outside of screening blood, male circumcision and drug treatment of mothers and infants at birth, the effectiveness of public health measures have been limited by compliance and cost. Particularly important in the path towards an HIV vaccine has been the Thai RV144 efficacy trials, which demonstrated that priming with a recombinant canary poxvirus (ALVAC) and boosting with ALVAC plus gp120 protein provided partial protection against HIV. In RV144, a non-neutralizing antibody was associated with reduced risk. Non-neutralizing antibodies, which can directly block infection, distinguish themselves from neutralizing antibodies by mediating protection via the fragment crystallizable (Fc) regions of bound antibody, triggering killing by innate immune responses, such as antibody-dependent cellular cytotoxicity, phagocytosis and complement-mediated killing. GeoVax (Atlanta, GA, USA) has developed clade B vaccines that have undergone phase I and IIa clinical testing in the Americas through the HIV Vaccine Trials Network.

Limited Impact of Passive Non-Neutralizing Antibody Immunization in Acute SIV Infection on Viremia Control in Rhesus Macaques

BackgroundAntiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus (HIV) infection. While neutralizing activity appears to be central in sterile protection against HIV infection, the entity of inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV)-specific antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in nonhuman primate models have indicated controversial protective efficacy of HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs). While reports on HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro, whether non-NAbs could also alter the pathogenic course of established SIV replication in vivo, likewise via neutralizing antibody (NAb) administration, has been unclear. Here, we performed post-infection passive immunization of SIV-infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell-mediated viral inhibition (ADCVI)-competent non-NAbs.Methods and FindingsTen lots of polyclonal immunoglobulin G (IgG) were prepared from plasma of ten chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI activity. A cocktail of three non-NAb lots showing high virion-binding capacity and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239 challenge. This resulted in an infection course comparable with control animals, with no significant difference in set point plasma viral loads or immune parameters.ConclusionsDespite virus-specific suppressive activity of the non-NAbs having been observed in vitro, their passive immunization post-infection did not result in SIV control in vivo. Virion binding and ADCVI activity with lack of virus neutralizing activity were indicated to be insufficient for antibody-triggered non-sterile SIV control. More diverse effector functions or sophisticated localization may be required for non-NAbs to impact HIV/SIV replication in vivo.

The HIV Epidemic Among Women in the United States: A Persistent Puzzle

The HIV Epidemic Among Women in the United States: A Persistent Puzzle

A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus

IntroductionMalaria, tuberculosis (TB) and human immunodeficiency virus (HIV) are diseases with devastating effects on global public health, especially in the developing world. Clinical trials of candidate vaccines for these diseases are being conducted at an accelerating rate, and require accurate and consistent methods for safety data collection and reporting. We performed a systematic review of publications describing the safety results from clinical trials of malaria, TB and HIV vaccines, to ascertain the nature and consistency of safety data collection and reporting. MethodsThe target for the review was pre-licensure trials for malaria, TB and HIV vaccines published in English from 2000 to 2009. Search strategies were customized for each of the databases utilized (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Database of Reviews and Effects). Data extracted included age of trial participants, vaccine platform, route and method of vaccine administration, duration of participant follow-up, reporting of laboratory abnormalities, and the type, case definitions, severity, reporting methods and internal reporting consistency of adverse events. ResultsOf 2278 publications screened, 124 were eligible for inclusion (malaria: 66, TB: 9, HIV: 49). Safety data reporting was found to be highly variable among publications and often incomplete: overall, 269 overlapping terms were used to describe specific adverse events. 17% of publications did not mention fever. Descriptions of severity or degree of relatedness to immunization of adverse events were frequently omitted. 26% (32/124) of publications failed to report data on serious adverse events. ConclusionsThe review demonstrated lack of standardized safety data reporting in trials for vaccines against malaria, TB and HIV. Standardization of safety data collection and reporting should be encouraged to improve data quality and comparability. LimitationsThe search strategy missed studies published in languages other than English and excluded studies reporting on vaccine trials for diseases besides malaria, TB and HIV.