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UNASSIGNED: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer.
UNASSIGNED: This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema.
UNASSIGNED: Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women.
UNASSIGNED: ClinicalTrials.gov identifier: NCT06165614.

We investigate an efficient computational tool to suggest useful treatment regimens for people infected with the human immunodeficiency virus (HIV). Structured treatment interruption (STI) is a regimen in which therapeutic drugs are periodically administered and withdrawn to give patients relief from an arduous drug therapy. Numerous studies have been conducted to find better STI treatment strategies using various computational tools with mathematical models of HIV infection. In this paper, we leverage a modified version of the double deep Q network with prioritized experience replay to improve the performance of classic deep learning algorithms. Numerical simulation results show that our methodology produces significantly more optimal cost values for shorter treatment periods compared to other recent studies. Furthermore, our proposed algorithm performs well in one-day segment scenarios, whereas previous studies only reported results for five-day segment scenarios.

Although highly active antiretroviral therapy (HAART) has changed infection with human immunodeficiency virus (HIV) from a diagnosis with imminent mortality to a chronic illness, HIV positive patients who do not develop acquired immunodeficiency syndrome (AIDs) still suffer from a high rate of cardiac dysfunction and fibrosis. Regardless of viral load and CD count, HIV-associated cardiomyopathy (HIVAC) still causes a high rate of mortality and morbidity amongst HIV patients. While this is a well characterized clinical phenomena, the molecular mechanism of HIVAC is not well understood. In this review, we consolidate, analyze, and discuss current research on the intersection between autophagy and HIVAC. Multiple studies have linked dysregulation in various regulators and functional components of autophagy to HIV infection regardless of mode of viral entry, i.e., coronary, cardiac chamber, or pericardial space. HIV proteins, including negative regulatory factor (Nef), glycoprotein 120 (gp120), and transactivator (Tat), have been shown to interact with type II microtubule-associated protein-1 β light chain (LC3-II), Rubiquitin, SQSTM1/p62, Rab7, autophagy-specific gene 7 (ATG7), and lysosomal-associated membrane protein 1 (LAMP1), all molecules critical to normal autophagy. HIV infection can also induce dysregulation of mitochondrial bioenergetics by altering production and equilibrium of adenosine triphosphate (ATP), mitochondrial reactive oxygen species (ROS), and calcium. These changes alter mitochondrial mass and morphology, which normally trigger autophagy to clear away dysfunctional organelles. However, with HIV infection also triggering autophagy dysfunction, these abnormal mitochondria accumulate and contribute to myocardial dysfunction. Likewise, use of HAART, azidothymidine and Abacavir, have been shown to induce cardiac dysfunction and fibrosis by inducing abnormal autophagy during antiretroviral therapy. Conversely, studies have shown that increasing autophagy can reduce the accumulation of dysfunctional mitochondria and restore cardiomyocyte function. Interestingly, Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has also been shown to reduce HIV-induced cytotoxicity by regulating autophagy-related proteins, making it a non-antiviral agent with the potential to treat HIVAC. In this review, we synthesize these findings to provide a better understanding of the role autophagy plays in HIVAC and discuss the potential pharmacologic targets unveiled by this research.

Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.

People living with human immunodeficiency virus (PLWH) are a significant population globally. Research delineating our understanding of coinfections in PLWH is critical to care for those navigating infection with other pathogens. The recent COVID-19 pandemic underscored the urgent need for studying the effects of SARS-CoV-2 infections in therapy-controlled and uncontrolled immunodeficiency viral infections. This study established the utility of a feline model for the in vivo study of coinfections. Domestic cats are naturally infected with SARS-CoV-2 and Feline Immunodeficiency Virus, a lentivirus molecularly and pathogenically similar to HIV. In this study, comparisons are made between FIV-positive and FIV-negative cats inoculated with SARS-CoV-2 (B.1.617.2.) in an experimental setting. Of the FIV+ cats, three received Zidovudine (AZT) therapy in the weeks leading up to SARS-CoV-2 inoculation, and two did not. SARS-CoV-2 viral RNA was quantified, histopathologic comparisons of respiratory tissues were made, and T-cell populations were analyzed for immune phenotype shifts between groups. CD4+ T lymphocyte responses varied, with FIV+-untreated cats having the poorest CD4+ response to SARS-CoV-2 infection. While all cats had significant pulmonary inflammation, key histopathologic features of the disease differed between groups. Additionally, viral genomic analysis was performed, and results were analyzed for the presence of emerging, absent, amplified, or reduced mutations in SARS-CoV-2 viral RNA after passage through the feline model. Positive selection is noted, especially in FIV+ cats untreated with AZT, and mutations with potential relevance were identified; one FIV+-untreated cat had persistent, increasing SARS-CoV-2 RNA in plasma five days post-infection. These findings and others support the utility of the feline model for studying coinfection in people with HIV and highlight the importance of antiretroviral therapy in clearing SARS-CoV-2 coinfections to minimize transmission and emergence of mutations that may have deleterious effects.

Human Immunodeficiency Virus (HIV) remains a significant global health challenge with approximately 38 million people currently having the virus worldwide. Despite advances in treatment development, the virus persists in the human population and still leads to new infections. The virus has a powerful ability to mutate and hide from the human immune system in reservoirs of the body. Current standard treatment with antiretroviral therapy effectively controls viral replication but requires lifelong adherence and does not eradicate the virus. This review explores the potential of Advanced Therapy Medicinal Products as novel therapeutic approaches to HIV, including cell therapy, immunisation strategies and gene therapy. Cell therapy, particularly chimeric antigen receptor T cell therapy, shows promise in preclinical studies for targeting and eliminating HIV-infected cells. Immunisation therapies, such as broadly neutralising antibodies are being investigated to control viral replication and reduce reservoirs. Despite setbacks in recent trials, vaccines remain a promising avenue for HIV therapy development. Gene therapy using technologies like CRISPR/Cas9 aims to modify cells to resist HIV infection or eliminate infected cells. Challenges such as off-target effects, delivery efficiency and ethical considerations persist in gene therapy for HIV. Future directions require further research to assess the safety and efficacy of emerging therapies in clinical trials. Combined approaches may be necessary to achieve complete elimination of the HIV reservoir. Overall, advanced therapies offer new hope for advancing HIV treatment and moving closer to a cure.

UNASSIGNED: Public sharing of de-identified biomedical data promotes collaboration between researchers and accelerates the development of disease prevention and treatment strategies. However, open-access data sharing presents challenges to researchers who need to protect the privacy of study participants, ensure that data are used appropriately, and acknowledge the inputs of all involved researchers. This article presents an approach to data sharing which addresses the above challenges by using a publicly available dashboard with de-identified, aggregated participant data from a large HIV surveillance cohort.
UNASSIGNED: Data in this study originated from the Rakai Community Cohort Study (RCCS), which was integrated into a centralized data mart as part of a larger data management strategy for the Rakai Health Sciences Program in Uganda. These data were used to build a publicly available, protected health information (PHI)-secured visualization dashboard for general research use.
UNASSIGNED: Using two unique case studies, we demonstrate the capability of the dashboard to generate the following hypotheses: firstly, that HIV prevention strategies ART and circumcision have differing levels of impact depending on the marital status of investigated communities; secondly, that ART is very successful in comparison to circumcision as an interventional strategy in certain communities.
UNASSIGNED: The democratization of large-scale anonymized epidemiological data using public-facing dashboards has multiple benefits, including facilitated exploration of research data and increased reproducibility of research findings.
UNASSIGNED: By allowing the public to explore data in depth and form new hypotheses, public-facing dashboard platforms have significant potential to generate new relationships and collaborations and further scientific discovery and reproducibility.

In recent years, virological, pathological, and immunological studies need to be carried out for the emerging anti-human immunodeficiency virus (HIV) therapies such as gene therapy, broadly neutralizing antibodies, and the derived chimeric antigen receptor (CAR)-T immunotherapy, which necessitates suitable, simple, and inexpensive small-animal models and methods for accurate quantification of the viral genome in the HIV-1 infected. In our research, the HIV-∆ENV-Jurkat-EGFP-mCherry cell line was engineered through the infection with a dual-labelled HIV pseudovirus. A nested quantitative PCR (nested-qPCR) method with the cellular genome as the integrated standard was established for the quantification of HIV proviral copies. We administered intravenous injections of healthy human peripheral blood mononuclear cell (PBMC) into NOD/Prkdcscid/IL2rgnull (NPG) mice. To verify engraftment kinetics, we analyzed the percentages of hCD45+, hCD3+, hCD4+, and hCD8+ cells in the peripheral blood of hu-PBMC-NPG mice. To evaluate HIV-1 infection in hu-PBMC-NPG mice, we inoculated these mice with HIV NL4-3-NanoLuc by intraperitoneal (IP) injection. We then monitored the luciferase expression by the small animal imaging system and measured the viral load in the spleen by qPCR. The infiltration of human PBMCs in mice was detected 3-5 weeks after intravenous injection, and the percentage of hCD45 in humanized mouse PBMCs were more than 25% five weeks after IP inoculation. The expression of the virus-associated luciferase protein was detected by luciferase imaging 27 days post infection. Moreover, the viral total DNA, RNA, and proviral DNA copies reached 18 000 copies/106 cells, 15 000 copies/μg RNA, and 15 000 copies/106 cells, respectively, in the mouse spleen. Taken together, we reported a convenient method for building a simple humanized mouse model of HuPBMC-NPG/severe combined immunodeficiency (SCID) by intravenous injection with hu-PBMCs without advanced surgical skills and irradiation. Furthermore, we established a convenient method for the efficient determination of proviral DNA to assess HIV replication in vivo, viral reservoir sizes, and efficacy of novel anti-HIV therapies including CAR-T immunotherapy and gene therapy.

OBJECTIVE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany.
METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany.
RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs.
CONCLUSIONS: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.