CURRENT HIV RESEARCH

Africa is an Essential Partner in the Research and Development of an HIV Vaccine
Gray G, Williamson C, Bekker LG, Daniels B, Smidt W, Garrett N, Kityo Mutuluuza C, Mwesigwa B, Stranix-Chibanda L, Akimbu A, Obuku A, Johnson T, Naluyima P, Sawe F, Burgers W, Ntiginya N, Morar N, Takalani A, Hendricks S, Woeber K, Abrahams F, Tholanah M, Mugamba S, Mulder M and Moore P
Despite significant advances in HIV antiretroviral treatment, and proven efficacy of HIV prevention options, an effective and affordable HIV vaccine is still necessary for the elimination of HIV, particularly in Africa. Furthermore, viral and host factors unique to the African continent provide a strong scientific rationale for local vaccine discovery efforts. Several key challenges hamper Africa's vaccine research and production capabilities. These include inadequate funding for African-led research, equipment and infrastructure challenges, lack of preclinical evaluation capacity, limited manufacturing facilities for clinical-grade vaccines, and a shortage of scientists with specialized laboratory, bioinformatics and biostatistics training. A recently established African-led consortium seeks to strengthen African HIV vaccine contributions by providing support, training and funding to address these gaps by strengthening discovery research and conducting early phase clinical trials of existing and novel Africa-derived vaccine candidates while strengthening African manufacturing infrastructure and capacity. Constant and robust community and stakeholder engagement will be key to ensuring the success of the consortiums' efforts in providing sustainable vaccine development, manufacturing and clinical testing in Africa. Given the magnitude of the HIV burden in Africa, with largely undescribed viral and host diversity, it is vital that HIV vaccine discovery evolves to include the underutilized scientific expertise and capacity on the African continent. Recent interruptions in the funding of consortia in Africa threaten this type of progress and can derail progress in vaccine discovery.
The Rising Impact of HPV Infection in the Antiretroviral Therapy (ART) Era
Asensi-Díaz E, Carrillo I, Al-Hayani A, Mejías-Ledesma M, Guadalajara H, Azinovic I, Trsitancho JLD, Vidal LS, Castellano V, García-Olmo D, Górgolas M and Cabello-Úbeda A
Since the introduction of antiretroviral therapy (ART), non-AIDS malignancies-particularly anal cancer-have increased in people living with HIV (PLHIV). However, associated risk factors and disease progression remain poorly defined.
Brain Abscess Caused by Nocardia sp. in an HIV Patient: A Case Report Highlighting Challenges and Treatment Success
Ghazawi TM, Alhazmi M, Bakri HA, Jaly AA, Shabi Y and Alhazmi AH
Nocardia brain abscess is a rare opportunistic infection in people living with HIV at an advanced stage. Immunosuppression, especially with very low CD4 counts and non-adherence to treatment, increases the risk. These infections are diagnostically challenging due to their nonspecific presentation and the limited sensitivity of routine molecular panels in detecting Nocardia.
Characterization of Early Viral Populations in Infants Acquiring HIV Through Perinatal and Breastmilk Transmission: A Review of what is Currently Known and the Gaps that Need to be Addressed to Guide Passive HIV Immunization of Breastfeeding Infants
Giorgi EE, Abrahams MR, Fouda G, John-Stewart G, Goga A, Mullins JI, Permar SR, Janes HE and Martin TM
Newborns represent only 1% of the population. Yet, HIV vertical transmissions represent 10% of all new infections globally, even though antiretroviral therapy (ART) has been shown to reduce the risk of vertical transmission to less than 2%. While vaccines still represent the most efficient and cost-effective intervention to eradicate new infections, HIV immunogens that can effectively elicit broad-spectrum protection are still at least a decade away. In contrast, passive immunization with broadly neutralizing antibody (bnAb) combinations has the potential to provide a more immediate pathway to HIV prophylaxis. Early-phase infant trials are underway to establish the safety and pharmacokinetics of bnAb combinations selected for their potency against viruses acquired via adult transmissions. However, the specific characteristics and phenotypic differences of vertically transmitted viruses in infants compared to those in adults remain uncertain, including their susceptibility to known broadly neutralizing antibodies (bnAbs). We review the current knowledge of vertically transmitted HIV viruses, including their genetics and phenotypic features. Differences in immunity between adults and infants lead us to hypothesize that distinct selection and evolutionary pressures act on the virus at the time of transmission and during the early phases of infection, and these may in turn affect the choice of bnAb combinations needed for protection against vertical transmission of HIV.
HIV-Associated Lymphomas: Updates from Pathogenesis to Treatment Strategies
Liu Y, Li J and Liu Y
HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lympho-mas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and on-cogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemo-therapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19-CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy tri-als. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticle-based drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision med-icine that integrates tumor genomics and viral dynamics.
Impact of HIV-1 Tat on FDFT1 Suppression, Changes in Cholesterol Level, and KSHV Replication in BCBL1 Cells
Liu Q, Chen X, Liu D, Zou Y, Yang W, Cao Z, Ding Y, Ji W, Xiao N, Tang H, Jiang Y, Wei L and Zeng Y
The present study investigated the molecular mechanism by which the transactivator of transcription (Tat) protein of Human Immunodeficiency Virus 1 (HIV-1) activates the replication cycle of Kaposi's Sarcoma-associated Herpesvirus (KSHV).
A Randomized Controlled Trial Evaluating Virologic and Renal Outcomes After Switching from TDF+FTC or 3TC+EFV to TDF/3TC/DTG (TLD) Versus DTG+3TC in Virologically Suppressed Thai PWH - A Pilot Study
Kanogtorn S, Putcharoen O and Patamatamkul S
Tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/dolutegravir (DTG) (TLD) is the preferred first-line therapy for all people living with HIV (PWH) per WHO 2019 and Thai HIV guidelines. This has prompted switches from TDF + FTC or 3TC + EFV to TLD in Thailand.
The Characteristics of Peripheral Blood Lymphocyte Subsets in HIV-related Diffuse Large B-cell Lymphoma Patients and Their Impact on Treatment Efficacy
Xiang H, Lin C, Chen S, Peng Y, Jiang T, Lin C, Xiao Q, Zhang X, Liu T, Li N, Tang X, Zhang Y, Liu J and Yang Z
Peripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4+/CD8+ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.
Advancing HIV Treatment Through Nanoparticles: A Precision Medicine Approach
Zubair A, Jawad M, Khan L, Hidayat Z and Ali M
The poor solubility and bioavailability of antiretroviral drugs complicate the manage-ment of Human Immunodeficiency virus. The efficacy of these medications is diminished due to restricted absorption in the gastrointestinal tract. Patients often exhibit a wide range of reactions attributable to fluctuations in blood drug concentrations. Achieving the target plasma concentra-tions is challenging and often necessitates higher dosages, which increases the risk of adverse ef-fects. The formulation of pharmaceuticals with poor solubility is a complex and costly process that hinders overall drug development. Given the limitations of traditional formulation strategies to address these issues, it is essential to explore alternative methods. The innovative method of nano-crystallization enhances the solubility and dissolution rates of pharmaceuticals by reducing their particle sizes to the nanoscale. The increased surface area improves the medication's solu-bility and bioavailability. Nanomedicine antiretroviral medications offer several advantages over their water-insoluble counterparts, including enhanced efficacy and safety, a higher drug load, and a more rapid onset of action. For this study, various databases, including Scopus, PubMed, Google Scholar, ScienceDirect, and Web of Science, were utilized to retrieve relevant literature on nanoparticles for HIV treatment. We examine the challenges associated with current treatment methods for HIV/AIDS and highlight the remarkable potential of nanotechnology to improve both the treatment and prevention of the disease through the development of antiretroviral therapy, gene therapy, immunotherapy, vaccinology, and microbicides. This review article focuses on var-ious nanomedicine approaches used to target HIV in different sites, including the spleen, liver, kidneys, gastrointestinal tract, lungs, and brain.
HIV-1 bNAb Vaccinal Effect - An Underachieving Goal?
King H, Roederer M and Bolton DL
Reports of HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) medi-ating a potential 'vaccinal effect' implicate passively transferred bNAbs in promoting endoge-nous anti-HIV-1 immune responses. To date, three clinical trials have reported either increased anti-HIV-1 neutralizing antibodies or T cell responses following bNAb administration to people living with HIV. Despite strong enthusiasm for this hypothesis, motivated in large part by its potential application to HIV-1 therapeutic strategies, the mechanism(s) underlying a vaccinal ef-fect remain unclear. Moreover, vaccinal effects on antibody and T cell responses are not consist-ently replicated. Partly, this inconsistency may be due to numerous difficulties in sensitively measuring a vaccinal effect in the context of human clinical trials. The magnitude of immune response increase following bNAb administration is generally modest, even when it is observed; a far greater enhancement of neutralization or T cell responses is likely required for a biologically meaningful impact. We review clinical and pre-clinical nonhuman primate studies that evaluated HIV-1/SIV monoclonal antibodies for vaccinal effects, with an emphasis on the strengths and limitations of these studies. Considerations for future studies investigating vaccinal effects are discussed, including appropriate comparators and specificity controls. Lastly, immune response characteristics of elite controller cohorts are outlined as potential vaccinal effect endpoints more likely to mediate HIV-1 suppression. As bNAb therapeutic interventions increasingly turn to combination approaches, including incorporation of immunomodulatory agents, attention to study design incorporating appropriate control groups, and relevant immunogenicity assays will enable more conclusive interpretation of vaccinal effects likely to mediate durable control of HIV. In any case, to date, the elicitation of vaccinal effects has been disappointing.
Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence
Fouda GG, Singh A, Nelson A, Janes H, Martin T, Levy O, Wu D, Zou F, Jean-Philippe P, De Paris K, Van Rompay KKA and Permar SR
An optimal HIV vaccine should provide protective immunity before sexual debut to prevent infection in adolescents and young adults, including acute infections in women of childbearing age. Such a vaccine will likely require multiple sequential immunization doses and would therefore be ideally initiated in childhood. Many of the world's most successful vaccines are initiated in childhood for the induction of lifelong immunity and/or immunity that can be boosted later in life as part of the WHO Expanded Program on Immunization (EPI). Thus, the EPI vaccine framework provides an infrastructure that could be leveraged for the implementation of a multidose HIV immunization regimen. Early childhood also provides a window of time in which there is minimal HIV exposure risk, and the plasticity of the early life immune landscape may present advantages for the elicitation of broadly neutralizing Antibodies (bnAbs), a primary target for HIV vaccination. Sequential vaccination with adjuvanted immunogens targeting spe-cific bnAb lineages is a promising HIV vaccine strategy, and several vaccine candidates are cur-rently being tested in adult clinical trials. It will be critical also to evaluate the most promising immunogens and adjuvants in pediatric settings. Preclinical studies, including in vitro and in sil-ico modelling as well as studies in animal models, will be essential to guide the design of future pediatric vaccine trials. This review summarizes current advances in bnAb germline targeting immunization. It provides the rationale for a better integration of preclinical and clinical vaccine studies to facilitate the development of a vaccine that achieves protective immunity in preadoles-cence.
Epidemiology of Kidney Disease in People Living with HIV in Türkiye; Comorbidities and Drug Toxicities are Emerging Problems
Eser F, Kayaaslan B, Şentürk GÇ, Sönmezer MÇ, Baştuğ A, Birengel S, İnkaya AÇ, Kuzi S, Hatipoğlu ÇA, Sarıcaoğlu EM, İskender G, Yenigün EC and Ünal S
To reveal the epidemiology of kidney disease (KD) in people living with HIV (PWLH) and to report the antiretroviral treatment (ART) management in case of kidney disease.
Innovative Single-Cell Sequencing Techniques for B-Cell Analysis and Their Implications for Rational HIV-1 Vaccine Design
Guerra D, Graus LTM, Beaumont T, Claireaux M and van Gils MJ
The application of single-cell analysis to investigate immune cell diversity has historically been considered a complex task. Recently, innovative techniques have emerged revolutionizing the way immune cells can be explored, offering unprecedented insights into the dynamics of this complex system. In particular, novel approaches have enabled a detailed characterization of B-cell responses, encompassing immune repertoire, gene expression, and phenotype analysis at an individual cell level. By analyzing single B-cells, researchers can unravel their heterogeneity, trace clonal evolution, and track immune responses during infections and vaccinations over time, gaining a deeper understanding of the mechanisms underlying antibody secretion and immune memory formation. This knowledge can inform the development of optimal immunogens, adjuvants, and vaccine platforms, which are crucial for inducing robust, long-lasting protective responses and overcoming existing challenges in vaccine research. This is particularly valuable for rational vaccine design against certain pathogens, such as human immunodeficiency virus [HIV-1], for which a successful vaccine remains to be developed due to the need to elicit rare broadly neutralizing antibodies that target conserved epitopes on the genetically diverse envelope glycoprotein trimer. This review will highlight the latest advancements in single-cell sequencing techniques and bioinformatic tools for the analysis of B-cell responses in the context of infectious diseases and vaccinations. Single-cell sequencing techniques, their applications, and their pivotal role in advancing the design of next-generation vaccines, especially in the context of HIV-1, will be discussed.
Sustained Delivery of Dolutegravir Sodium for Better Management of HIV/AIDS via Solid Lipid Nanoparticles
Singh M, Kedar P, Kanugo A and Bukkawar A
Human immunodeficiency virus (HIV) is a primary health concern that leads to Acquired immunodeficiency syndrome (AIDS), with more than 39.9 million people living with HIV globally. Dolutegravir sodium is a lipophilic compound with a log P value of 2.2. The current research aimed at augmenting the solubility, dissolution, and therapeutic benefits of Dolutegravir sodium through Solid lipid nanoparticles.
Toxoplasma gondii Coinfection in HIV-Positive Patients at a Tertiary Care Hospital
Kürkçü MF, Bakır A, Kaba SBT, Kuşabbi İA and Usluca S
Toxoplasma gondii (T. gondii) can cause serious complications in both immunocompetent and immunosuppressed individuals. This study aims to assess the seroprevalence of T. gondii among HIV-positive individuals and to investigate its association with age, sex, CD4+ T cell count, HIV RNA levels, and hematological parameters.
Unveiling an Immunological Mystery: Deciphering the Durability Divide in Vaccine-Elicited Antibody Responses
Lewis GK, Ciupe S and Sajadi M
Achieving durable antibody-mediated protection remains critical in vaccine develop-ment, particularly for viral diseases like COVID-19 and HIV. We discuss factors influencing an-tibody durability, highlighting the role of long-lived plasma cells (LLPCs) in the bone marrow, which are essential for sustained antibody production over many years. The frequencies and prop-erties of bone marrow LLPC are critical determinants of the broad spectrum of antibody durability for different vaccines. Vaccines for diseases like measles and mumps elicit long-lasting antibod-ies; those for COVID-19 and HIV do not. High epitope densities in the vaccine are known to favor antibody durability, but we discuss three underappreciated variables that also play a role in long-lived antibody responses. First, in addition to high epitope densities, we discuss the im-portance of CD21 as a critical determinant of antibody durability. CD21 is a B cell antigen recep-tor (BCR) complex component. It significantly affects BCR signaling strength in a way essential for generating LLPC in the bone marrow. Second, all antibody-secreting cells (ASC) are not cre-ated equal. There is a four-log range of antibody secretion rates, and we propose epigenetic im-printing of different rates on ASC, including LLPC, as a factor in antibody durability. Third, antibody durability afforded by bone marrow LLPC is independent of continuous antigenic stim-ulation. By contrast, tissue-resident T-bet+CD21low ASC also persists in secondary lymphoid tissues and continuously produces antibodies depending on persisting antigen and the tissue mi-croenvironment. We discuss these variables in the context of making an HIV vaccine that elicits broadly neutralizing antibodies against HIV that persist at protective levels without continuous vaccination over many years.
Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development
Diazgranados CA, Onami T and Anklesaria P
This review outlines the Gates Foundation's investments in support of global efforts dedicated to the research and development of a safe, highly effective, prophylactic HIV vaccine. Our current Collaboration for AIDS Vaccine Discovery (CAVD) portfolio encompasses a wide range of initiatives, including projects aimed at eliciting broadly neutralizing antibodies, enhanc-ing CD8 T cell responses, and, through central service facilities, developing innovative analytical tools and animal models to assess immune responses. One central service facility also offers prod-uct development services to translate preclinical findings into clinical trials. Additionally, we are investing in platforms designed for the controlled release of HIV immunogens, simplifying com-plex vaccine regimens. Our ultimate objective is to develop a highly efficacious, safe, and durable vaccine that ensures broad access, uptake, and affordability. Furthermore, we emphasize the crit-ical importance of fostering global partnerships, with a focus on supporting research capacity in low- and middle-income countries. By making intentional investments, we aim to stimulate sus-tainable research and development in the regions most affected by the HIV epidemic.
Attributes Associated with HIV Risk Behaviors in a Network-Based Study of People Who Inject Drugs
Ryan V, Lee T, Piovani D, Katenka N, Friedman SR, Bonovas S, Buchanan A and Nikolopoulos G
People who inject drugs (PWID) are often part of sexual and drug use networks. Engaging in unprotected sex or sharing drug injection equipment, which could occur between connections (ties) in these networks, is known to increase HIV transmission risk. This study aimed to identify attributes associated with network connections between PWID and their contacts during an HIV outbreak in Athens, Greece (2013-2015).
Assessment of Brain Volume and Cortical Thickness in People with HIV and Major Depressive Disorder
Aşçıbaşı K, Atalay S, Albayrak Uçak H and Burhanoğlu BB
This study aims to examine neuroanatomical differences associated with depressive symptoms in people with HIV (PWH) by comparing three groups: depressed PWH (PWH Dep+), non-depressed PWH (PWH Dep-), and HIV-negative controls. The primary goal is to explore specific alterations in brain volume and cortical thickness linked to depressive symp-tomatology in PWH.
Genotypic Diversity and Pre-Treatment Resistance Characteristic Analysis Among Newly Diagnosed HIV-1-Positive MSM from 2020-2022 in Jiaxing City, China
Zhang X, Ren G, Ge Z, Lv S, Li P, Song Y, Jia M, Zhou Y, Yan Y and Zhu G
Since the first recorded HIV-1 infection in 1998, Jiaxing City has seen increasing HIV infections among men who have sex with men (MSM), necessitating targeted research to understand HIV-1 subtypes and drug resistance patterns to improve prevention and treatment strategies.
Family Support and Depression among Adolescents Living with HIV in Northern Nigeria
Umar AI, Olawumi AL, Ogunyele TT, Magaji HY, Suleiman AK, Grema BA, Wester CW and Aliyu MH
Family support is an important component of family-oriented care and a vital element in the care of patients with chronic illnesses, including HIV/AIDS. We investigated the association between perceived family support and depression among adolescents living with HIV in northern Nigeria.