Human Immunodeficiency Virus Research Research Articles

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Four Decades of HIV: Global Trends, Testing Assays, Treatment, and Challenges

More than 77 million individuals have been infected with the human immunodeficiency virus (HIV) and approximately 37.6 million people are living with HIV infection. HIV infection may increase susceptibility to cancer, cardiovascular disease, bone disease, and other co-morbid conditions. Antiretroviral (ARV) drugs are extremely potent HIV replication inhibitors. Combination ARV therapy suppresses the viral load and prolongs the lifespan of individuals who can acquire and adhere to ARV drug regimens. Indeed, viral suppression can nearly eliminate the risk of developing acquired immune deficiency syndrome (AIDS). ARV drugs reduce the risk of HIV transmission in uninfected individuals. In addition to a vital role in prevention strategies, viral transmission is still common in unprotected populations, especially in injection drug users, female sex workers, men who have sex with men (MSM), and transgender individuals. The history and timeline provide key milestones in HIV research leading to improved and advanced approaches to resolve the issue of HIV transmission. Nevertheless, it is essential to pursue breakthroughs, innovative treatments, improved prevention methods, and the development of vaccines. This article summarizes the 40-year timeline of HIV, testing assays, global burden, prevalence, treatment, and challenges related to HIV/AIDS.

Health-related quality of life among people living with HIV in the era of universal test and treat: results from a cross-sectional study in KwaZulu-Natal, South Africa

Background The World Health Organisation’s (WHO) key population-based strategy for ending the human immunodeficiency virus (HIV) epidemic is universal HIV test and treat (UTT) along with pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Despite the successful scale-up of the UTT strategy in sub-Saharan Africa (SSA), the quality of life (QoL) of people living with HIV (PLHIV) remains sub-optimal. Poor QoL in PLHIV may threaten the UNAIDS 95-95-95 programme targets. Monitoring QoL of PLHIV has become a key focus of HIV research among other outcomes so as to understand health-related QoL (HRQoL) profiles and identify interventions to improve programme performance. This study aimed to describe HRQoL profiles and identify their predictors in PLHIV in KwaZulu Natal, South Africa. Methods We conducted a secondary data analysis of a cross-sectional survey conducted between May and June 2022 among PLHIV (n = 105) accessing HIV services at an outpatient clinic in KwaZulu-Natal, South Africa. Socio-demographic, HRQoL (EQ-5D-5L index scores), clinical data, depressive symptoms (CES-D-10), and viral load data were collected from all participants. We examined predictors of HRQoL using generalised linear models controlling for age and sex. Results The mean age of the participants was 45 years (SD = 13). The proportion of participants with disabilities and comorbidities were 3% and 18%, respectively. Depressive symptoms were present in 49% of the participants. Participant’s mean EQ-5D-5L index score was 0.87 (SD = 0.21) and ranged from 0.11 to 1.0. The mean general health state (EQ-VAS) was 74.7 (SD = 18.8) and ranged from 6 to 100. Factors that reduced HRQoL were disability (β = −0.607, p ≤ 0.001), comorbidities (β = − 0.23, p ≤ 0.05), presence of depressive symptoms (β = −0.10, p ≤ 0.05), and old age (β = −0.04, p ≤ 0.05). Factors that increased HRQoL were a good perceived health state (β = 0.147, p ≤ 0.001) and availability of social support (β = 0.098, p ≤ 0.05). Conclusion A combination of old age (60 years and above), any disability and comorbidities had a considerable effect on HRQoL among PLHIV. Our findings support the recommendation for an additional fourth UNAIDS target that should focus on ensuring that 95% of PLHIV have the highest possible HRQoL. Psycho-social support interventions are recommended to improve the HRQoL of PLHIV.

Measures to improve participation of registered nurses in HIV and AIDS research.

Registered nurses are crucial in lowering the complications of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Nigeria. Human immunodeficiency virus infects individuals and impairs the immune system, impairing the body's capacity to fight bacteria, viruses, and other pathogens. Therefore, registered nurse-led initiatives are beneficial in promoting HIV and AIDS research development. However, these evidence-based treatments and professional expectations for registered nurse research creation do not represent contemporary research development on HIV and AIDS by registered nurses. This study aimed to explore measures to improve the participation of registered nurses in HIV and AIDS research in Nigeria. The study was conducted at a general hospital in Ijebu Ode, Ogun State, Nigeria. A qualitative approach design was employed. Participants of the study comprised 31 registered nurses in three focus groups. This study demonstrated the importance of research in effectively reducing HIV and AIDS transmission and maintaining good practices in a hospital setting in Nigeria. However, this understanding did not translate into knowledge creation through autonomous research productivity in this context. The study discovered that registered nurses were primarily involved in data collection and validation, which did not result in publications. The study found that registered nurses in Nigeria are typically worried about ways to promote nurses' engagement in research in Nigeria. These results might be utilised to improve the supply of research services and act as a baseline for future research linked to HIV and AIDS transmission prevention in Nigeria.

Global Research Output Human Immunodeficiency Virus From 1954-2022: Literature Review

HIV (human immunodeficiency virus) have two primary HIV strains are HIV-1 and HIV-2. Both can lead to AIDS and our work is explained to easily find out the data about HIV. We conducted the research work of HIV between the years of 1954-2022. We classified the models by their mathematical structure and research question. The amount of information that researchers are analyzing from etiology, pathogenesis, in-vivo, in-vitro, and human trials grows daily. As compared data for the HIV research and review work the research will perform moderately with the review work. The In-vivo and the In-vitro work are performed little lower than the other work. This is the useful research review source for the HIV research work. We created a segregation of desirable features of models, reviewed and classified the articles to inform our conclusions.

Outbreak-Associated Cases Of Human Hepatitis Viruses (HAV, HBV & HCV) With Herpes Simplex Virus And HIV Infections Detected in Blood-Based Biomarkers

Hepatitis A vaccines are based on classic first-generation inactivated virus vaccines and have been developed by different biopharmaceuticals. HAV is found in the stool, blood of people who are infected and foodborne hepatitis. HBV is a short-term disease and is one of the major causative agents of chronic liver illness.  For others, it can become a long-term, chronic infection like liver disease or liver cancer. The analysis of genomic variability of HBV isolates is fundamental for molecular and epidemiological studies. HCV has a higher rate of mutation existing inside an individual as quasispecies. In this sense, this study addresses an analysis of viral hepatitis A/B/C, Herpervirus Simplex (HSV) type 1/2 and the human immunodeficiency virus (HIV) as topics related to comprehensive care for people with sexually transmitted infections (STIs). A total of 2.750 samples were collected from 2.713 patients, of which 38,43% were for HCV; 31,20% for HIV research; 30,25% for HAV and 0,10% for HSV. In all, eight biomarkers of the hepatitis B virus (HBV) were investigated, of which the HBsAg marker was non-reactive in 44,01% (2022 y) and 47.66% (2023 y). About 31,41% (2022 y) and 31.99% (2023y) were reactive for anti-HBs. The highest percentage of investigated samples (98.38%) was recorded in March 2022 with a average proportion of 55.25 ± 12.96 (CV = 0.234) for the non reactive IgM biomarker. The authors suggest follow-up with new serological research associated with molecular assays aimed specifically at reactive and inconclusive results.

Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.

Human immunodeficiency virus (HIV) has infected millions of people worldwide and continues to be a major global health problem. Scientists required a small animal model to study HIV pathogenesis and immune responses. To this end, humanized mice were created by transplanting human cells and/or tissues into immunodeficient mice to reconstitute a human immune system. Thus, humanized mice have become a critical animal model for HIV researchers, but with some limitations. Current conventional humanized mice are prone to death by graft versus host disease induced by the mouse signal regulatory protein α and CD47 signaling pathway. In addition, commonly used humanized mice generate low levels of human cytokines required for robust myeloid and natural killer cell development and function. Here, we describe recent advances in humanization procedures and transgenic and knock-in immunodeficient mice to address these limitations.

The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?

In the early 2000s, novel humanized mouse models based on the transplantation of human hematopoietic stem and progenitor cells (HSPCs) into immunocompromised mice were introduced (hu mice). The human HSPCs gave rise to a lymphoid system of human origin. The HIV research community has greatly benefitted from these hu mice. Since human immunodeficiency virus (HIV) type 1 infection results in a high-titer disseminated HIV infection, hu mice have been of great value for all types of HIV research from pathogenesis to novel therapies. Since the first description of this new generation of hu mice, great efforts have been expended to improve humanization by creating other immunodeficient mouse models or supplementing mice with human transgenes to improve human engraftment. Many labs have their own customized hu mouse models, making comparisons quite difficult. Here, we discuss the different hu mouse models in the context of specific research questions in order to define which characteristics should be considered when determining which hu mouse model is appropriate for the question posed. We strongly believe that researchers must first define their research question and then determine whether a hu mouse model exists, allowing the research question to be studied.

Nurses' awareness of the availability of HIV and AIDS research.

Hardship of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) transmission in Nigeria needs research-based strategies that scientifically inform research findings for relevant research advocacy. This study aimed to enhance nurses' awareness of the availability of HIV and AIDS research in Nigeria. The research was carried out in a general hospital, a tertiary hospital in Ijebu Ode, Ogun State, Nigeria. A qualitative technique was used, as well as an exploratory-descriptive design was employed. Semi-structured interviews were carried out. Three focus group interviews with seven participants in each group were used to gather data. This study showed the value of nurses' awareness of the availability of HIV and AIDS research in overcoming obstacles to successfully controlling HIV and AIDS transmission in a hospital context in Nigeria. The study results demonstrated the nurses' understanding of local and global research. The result of the study also demonstrated the essential role of collaboration with partners in enhancing nurses' awareness of the availability of HIV and AIDS research in Nigeria. The study found that nurses in Nigeria were usually unaware of their role in healthcare research development in the context of HIV and AIDS. They preferred to go with the flow of events. This study affirms the importance of nurses' awareness of the availability of HIV and AIDS research in overcoming obstacles to successfully controlling HIV and AIDS transmission in a hospital context in Nigeria.

Adolescent and young adult research across the HIV prevention and care continua: an international programme analysis and targeted review

Human immunodeficiency virus (HIV) continues to rise in young people among low- and middle-income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings. NIH-funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012-2017 and 2018-2021. The review included a landscape assessment and an evaluation of NIH-defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed. Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH-defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub-Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions. Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC3 H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC.

A 16-color full spectrum flow cytometric analysis for comprehensive evaluation of T-cell reconstitution in SIV-infected rhesus macaques

T-cell reconstitution is central in human immunodeficiency virus (HIV) infection/disease progression. Simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) have been the most widely used animal model for HIV research so far. An effective flow cytometry panel is crucial for monitoring the T cell reconstitution in SIV infection progression. We developed this sixteen-color flow cytometry-based panel for a T cell subsets analysis by manual gating and, once successfully gated, to characterize T cells function in-depth in rhesus macaques. This panel included markers to characterize CD4+ T cells and CD8+ T cells, T regulatory cells (Tregs), and T cell differentiation status (CD45RA and CCR7). Additionally, we included antibodies that measure T cell activation and proliferation molecules (CD69, HLA-DR, CD38 and Ki67), antibodies that examine the expressions of key PD-1 pathway molecule (PD-1), SIV potential target (CD32) and the primary SIV co-receptor CCR5 (CD195). High-dimensional single cell analysis was also performed to identify CD3+ T cells immunophenotypes of SIV-infected rhesus macaques. We designed this panel to evaluate the responses of different T cell subsets to SIV in whole blood from SIV-infected rhesus macaques.

Peptide-based Fusion Inhibitors for Preventing the Six-helix Bundle Formation of Class I Fusion Proteins: HIV and Beyond.

A number of different viral families have developed convergent methods to infect cells. Class I fusion proteins are commonly used by members of Arenaviridae, Coronaviridae, Filovirdae, Orthomyxoviridae, Paramyxoviridae, and Retroviridae. Class I viral fusion proteins are trimers that are involved in recognizing the cellular receptor, with a region that is responsible for fusing the viral and target cell membranes. During the fusion process, the fusion region folds into a six-helix bundle (6 HB) which approximates the two membranes leading to fusion. For Human Immunodeficiency Virus (HIV), the gp41 subunit is responsible for the formation of this 6 HB. The fusion inhibitor drug enfuvirtide, or T20, is the only US Food and Drug Administration and European Medicines Agency approved drug which targets this crucial step and has been widely used in combination regimens for the treatment of HIV since March 2003. In this review, we describe the current state of peptide-based fusion inhibitors in the treatment of HIV, and review how the field of HIV research is driving advances in the development of similar therapeutics in other viral systems, including the Severe Acute Respiratory Syndrome (SARS) coronaviruses.

Perceptions of HIV Research Participation Among Gay, Bisexual, and Other Men who Have Sex with Men and Transgender and Nonbinary Adults: Results From a Midwest Pride Event

Human immunodeficiency virus (HIV) continues to disproportionately affect gay, bisexual, and other men who have sex with men (GBM) and transgender and nonbinary (trans/NB) individuals. This study investigated attitudes toward participation in HIV survey research, guided by Emanuel's framework for ethical clinical research (e.g., risk-benefit ratio, fair participant selection, respect for participants, social value, and collaborative partnership). GBM (n = 294) and trans/NB (n = 86) persons recruited at a Pride event in Milwaukee completed a survey assessing risks and benefits of participation in, and comfort responding to, sexual health surveys. Participants reported few ethical concerns (e.g., privacy and confidentiality), with notable differences by race, sexual orientation and gender identity, and prior research experiences. Implications for HIV research with GBM and trans/NB individuals are discussed.

The impact of COVID-19 on mentoring early-career investigators: "Everything can wait. Listen more than usual and share your own struggles".

The COVID-19 pandemic disrupted almost all sectors of academic training and research, but the impact on human immunodeficiency virus (HIV) research mentoring has yet to be documented. We present the perspectives of diverse, experienced mentors in a range of HIV research disciplines on the impact of COVID-19 on mentoring the next generation of HIV researchers.In November to December, 2020, we used an online data collection platform to cross-sectionally query previously-trained HIV mentors on the challenges related to mentoring during the pandemic, surprising/positive aspects of mentoring in that context, and recommendations for other mentors. Data were coded and analyzed following a thematic analysis approach.Respondents (180 of 225 mentors invited [80% response]) reported challenges related to relationship building/maintenance, disruptions in mentees’ training and research progress, and mentee and mentor distress, with particular concerns regarding mentees who are parents or from underrepresented minority backgrounds. Positive/surprising aspects included logistical ease of remote mentoring, the relationship-edifying result of the shared pandemic experience, mentee resilience and gratitude, and increased enjoyment of mentoring. Recommendations included practical tips, encouragement for patience and persistence, and prioritizing supporting mentees’ and one's own mental well-being.Findings revealed gaps in HIV mentors’ competencies, including the effective use of remote mentoring tools, how to work with mentees in times of distress, and the prioritization of mentor well-being. Mentors are in a unique position to identify and potentially address factors that may lead to mentees leaving their fields, especially parents and those from underrepresented backgrounds. We discuss implications beyond the COVID-19 pandemic.

Pre-exposure Prophylaxis in HIV Research: A Latent Dirichlet Allocation Analysis (GAPRESEARCH).

Pre-exposure prophylaxis (PrEP) has been shown to be an effective approach to prevent human immunodeficiency virus (HIV) infections; however, implementation of the service remains challenging. This global bibliometric analysis aims to describe the current trends in HIV research prevention through PrEP to reveal the potential gaps of knowledge and to put forward recommendations for future research. A bibliometric analysis was conducted through Web of Science from 1990 to 2017. Exploratory factor analysis was also employed to find research domains emerging from the abstracts' contents. Latent Dirichlet allocation, which is a topic modeling algorithm, was utilized to perform text mining and determine relationships among text documents. A total of 4852 papers regarding HIV PrEP research were retrieved. The number of papers and their impact has significantly increased. Preventing sexual transmissions, improving access, and quality of health-care services for current users, as well as men who have sex with men, pregnant women and children, were the research domains most related to PrEP. We found a data gap in research regarding sex workers, potential side effects of PrEP, and misjudgment toward PrEP users. Despite the growth in research about HIV PrEP, there exist barriers to scaling up the implementation of PrEP worldwide and for such intervention to reach its fWull potential. International research collaboration efforts to investigate the potential safety concerns of PrEP and develop strategies to eliminate social misjudgment against PrEP users are warranted. Addressing these knowledge gaps might facilitate the development of effective global implementation strategies for PrEP in the future.

Alcohol Use and the Risk of Communicable Diseases.

The body of knowledge on alcohol use and communicable diseases has been growing in recent years. Using a narrative review approach, this paper discusses alcohol’s role in the acquisition of and treatment outcomes from four different communicable diseases: these include three conditions included in comparative risk assessments to date—Human Immunodeficiency Virus (HIV)/AIDS, tuberculosis (TB), and lower respiratory infections/pneumonia—as well as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) because of its recent and rapid ascension as a global health concern. Alcohol-attributable TB, HIV, and pneumonia combined were responsible for approximately 360,000 deaths and 13 million disability-adjusted life years lost (DALYs) in 2016, with alcohol-attributable TB deaths and DALYs predominating. There is strong evidence that alcohol is associated with increased incidence of and poorer treatment outcomes from HIV, TB, and pneumonia, via both behavioral and biological mechanisms. Preliminary studies suggest that heavy drinkers and those with alcohol use disorders are at increased risk of COVID-19 infection and severe illness. Aside from HIV research, limited research exists that can guide interventions for addressing alcohol-attributable TB and pneumonia or COVID-19. Implementation of effective individual-level interventions and alcohol control policies as a means of reducing the burden of communicable diseases is recommended.

A GEE Approach for Estimating Correlation Coefficients Involving Left-censored Variables

HIV (Human Immunodeficiency Virus) researchers are often con cerned with the correlation between HIV viral load measurements and CD4+ lymphocyte counts. Due to the lower limits of detection (LOD) of the avail able assays, HIV viral load measurements are subject to left-censoring. Mo tivated by these considerations, the maximum likelihood (ML) method under normality assumptions was recently proposed for estimating the correlation between two continuous variables that are subject to left-censoring. In this paper, we propose a generalized estimating equations (GEE) approach as an alternative to estimate such a correlation coefficient. We investigate the robustness to the normality assumption of the ML and the GEE approaches via simulations. An actual HIV data example is used for illustration.

PIN80 Understanding Real-World Utilization of Pre-Exposure Prophylaxis (PrEP): Data from Trio Health HIV Research Network

In February 2019, the US Department of Health and Human Services proposed a strategic initiative to end human immunodeficiency virus (HIV) epidemic in the US by reducing new HIV infections by 90% in 2020–2030. One of the 4 pillars of the initiative is protecting persons at risk for HIV infection using HIV PrEP (antiretrovirals proven effective at preventing infection among persons at risk). We investigated PrEP uptake, adherence, and discontinuation among patients in care at 11 large geographically distributed US HIV treatment centers. Trio Health HIV Research Network containing electronic medical records for over 130,000 HIV and non-HIV patients was used for the study. PrEP patient registry contains nearly 9,000 patients with PrEP prescriptions and over 5,000 with PrEP dispenses. Of 5,223 adults with PrEP dispensing data, 66% were male, 4% female, <1% transgender, and 30% unspecified gender; 59% were white, 12% black, 10% other race, 19% unknown; 86% were age <50 at PrEP initiation. Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) was dispensed to 81% of patients, FTC/tenofovir alafenamide (TAF) to 47%. Average PrEP duration was 10.2 mo (SD 9.9): 12 mo (11.6) FTC/TDF, 7.2 mo (4.4) FTC/TAF. Average medication possession ratio was 88%: 87% for FTC/TDF, 93% for FTC/TAF. Trio Health HIV Research Network is dynamic data collection that provides insight into patterns of PrEP prescribing and dispensing, patient experience and adherence, longitudinal changes in comorbidities and laboratory values, frequency and time to seroconversion. Continued collection and analyses of patient data will broaden PrEP awareness and optimize patient outcomes.

Characteristics of REPRIEVE Trial Participants Identifying Across the Transgender Spectrum.

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.7% overall, 2.4% among natal males, 0.3% among natal females, and varied across geographic regions (from 0% in sub-Saharan Africa to 2.3% in High Income Region). Thirty percent of natal male PATS identified other than transgender. Some characteristics differed by gender. Most notably, 38% of natal male PATS receiving gender-affirming treatment had waist circumference >102 cm (compared with ≤25% in other groups). Given that PATS is a key population, HIV research should routinely report trial participation and outcomes by gender in addition to natal sex, to provide the results needed to optimize medical care to PATS.

Lessons learnt conducting minimally invasive autopsies in private mortuaries as part of HIV and tuberculosis research in South Africa

Current estimates of the burden of tuberculosis (TB) disease and cause-specific mortality in human immunodeficiency virus (HIV) positive people rely heavily on indirect methods that are less reliable for ascertaining individual-level causes of death and on mathematical models. Minimally invasive autopsy (MIA) is useful for diagnosing infectious diseases, provides a reasonable proxy for the gold standard in cause of death ascertainment (complete diagnostic autopsy) and, used routinely, could improve cause-specific mortality estimates. From our experience in performing MIAs in HIV-positive adults in private mortuaries in South Africa (during the Lesedi Kamoso Study), we describe the challenges we faced and make recommendations for the conduct of MIA in future studies or surveillance programmes, including strategies for effective communication, approaches to obtaining informed consent, risk management for staff and efficient preparation for the procedure.