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1.
J Theor Biol ; 594: 111914, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39111541

ABSTRACT

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 Structured treatment interruption (STI) is a regimen in which therapeutic drugs are periodically administered and withdrawn to give patients relief from an arduous drug therapy.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.

2.
Front Cell Dev Biol ; 12: 1372573, 2024.
Article in English | MEDLINE | ID: mdl-39086659

ABSTRACT

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 ß 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.

3.
Quant Imaging Med Surg ; 14(7): 4675-4687, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39022222

ABSTRACT

Background: People infected with human immunodeficiency virus (PIWH) have a higher risk of cardiovascular events. This study was designed to compare the differences in plaque characteristics and perivascular fat between subclinical coronary atherosclerosis in PIWH and healthy controls (HC) by coronary computed tomography angiography (CCTA). We also assessed the associations between human immunodeficiency virus (HIV) infection, antiretroviral therapy (ART), and coronary artery disease (CAD). Methods: This cross-sectional study included a total of 158 PIWH and 79 controls. CCTA was used to evaluate coronary artery plaque prevalence, coronary stenosis severity, plaque composition, plaque volume, and perivascular fat attenuation index (FAI). Logistic regression analyses were used to assess the associations between the prevalence of coronary artery plaque and HIV-related clinical indicators. Results: There was no difference in total coronary artery plaque prevalence between PIWH and controls (44.3% vs. 32.9%; P=0.09), but the prevalence of noncalcified plaque was significantly higher in PIWH compared with the controls (33.5% vs. 16.5%; P=0.006). After adjustment for age, sex, statin use, and family history of cardiovascular disease (CVD), the prevalence of noncalcified plaque remained 2 times higher in PIWH [odds ratio (OR), 2.082; 95% confidence interval (CI): 1.007-4.304; P=0.048]. The perivascular FAI measured around the left anterior descending artery (LAD) was higher in PIWH (-71.4±5.7 vs. -73.5±7.0; P=0.03) compared with that of the controls. The intra-group analyses of PIWH suggested that the decrease in nadir CD4+ T-cell count was associated with the increased prevalence of noncalcified plaque (OR, 4.139; 95% CI: 1.312-13.060; P=0.02). Conclusions: PIWH have a higher risk of developing noncalcified plaque and greater perivascular fat. In addition, the increased noncalcified plaque prevalence in PIWH may be associated with the immunodeficiency caused by HIV.

4.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2195-2210, 2024 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-39044584

ABSTRACT

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.


Subject(s)
DNA, Viral , Disease Models, Animal , HIV Infections , HIV-1 , Proviruses , Animals , HIV-1/genetics , HIV-1/immunology , Mice , Humans , Proviruses/genetics , HIV Infections/immunology , HIV Infections/virology , DNA, Viral/genetics , Mice, Inbred NOD , Mice, SCID , Leukocytes, Mononuclear/immunology , Viral Load
5.
Infection ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042326

ABSTRACT

PURPOSE: 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. CONCLUSION: 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.

6.
Med Sci (Basel) ; 12(3)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39051379

ABSTRACT

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.


Subject(s)
Genetic Therapy , HIV Infections , Humans , Cell- and Tissue-Based Therapy , Virus Replication , HIV
7.
JAMIA Open ; 7(3): ooae069, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39044942

ABSTRACT

Objectives: 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. Materials and Methods: 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. Results: 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. Discussion: 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. Conclusion: 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.

8.
J Clin Immunol ; 44(7): 163, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008214

ABSTRACT

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.


Subject(s)
Antibodies, Neutralizing , Autoantibodies , Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Autoantibodies/blood , Autoantibodies/immunology , Male , Colombia , Female , Adult , Cryptococcus gattii/immunology , Middle Aged , Cryptococcus neoformans/immunology , Cryptococcosis/immunology , Cryptococcosis/diagnosis , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Retrospective Studies , HIV Seronegativity/immunology , Young Adult , Aged
9.
Vaccines (Basel) ; 12(7)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39066420

ABSTRACT

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.

10.
Cureus ; 16(6): e61562, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38962632

ABSTRACT

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

11.
Front Public Health ; 12: 1366795, 2024.
Article in English | MEDLINE | ID: mdl-38962784

ABSTRACT

Background: Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs). Objective: This study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China. Method: We conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load <50 copies/mL) were included in the study. Data were collected from the National Epidemiological Database of Zhejiang Province and all participants were tested for viral load and current syphilis. Multivariable logistic regression was used to identify risk factors associated with current syphilis infection. Result: A total of 30,744 participants were included in the analysis. 82.7% of participants were male, the mean age was 44.9 ± 14.1 years, 84.9% had received ART in a hospital setting, the mean time on ART was 5.9 ± 3.1 years and 5.6% of participants were infected with current syphilis. Multivariable logistic regression showed that being male [adjusted odds ratio (aOR): 2.12, 95% confidence interval (CI): 1.69-2.66], high level of education (aOR: 1.23, 95% CI: 1.02-1.49), homosexual route of HIV infection (aOR: 1.80, 95% CI: 1.60-2.04), non-local registered residence (aOR: 1.29, 95% CI: 1.11-1.51), had history of STIs before HIV diagnosis (aOR: 1.95, 95 % CI: 1.75-2.18) and treatment provided by a municipal hospital (aOR: 2.16, 95% CI: 1.31-3.55) were associated with increased risk of current syphilis infection. Being married (aOR: 0.67, 95% CI: 0.58-0.76) was associated with a decreased risk of current syphilis infection. Conclusion: Our findings revealed a high rate of current syphilis infection among virally suppressed PLWH in eastern China. Duration of ART did not reduce the prevalence of current syphilis infection. Targeted interventions to reduce current syphilis infection should be prioritized for subgroups at higher risk.


Subject(s)
HIV Infections , Syphilis , Viral Load , Humans , Syphilis/epidemiology , Cross-Sectional Studies , Male , Adult , HIV Infections/epidemiology , HIV Infections/complications , Female , China/epidemiology , Middle Aged , Risk Factors
12.
Microorganisms ; 12(7)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39065058

ABSTRACT

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.

13.
Health Sci Rep ; 7(6): e2206, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38933421

ABSTRACT

Background: Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM. Methods: This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and I 2 along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764). Results: Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly. Conclusion: There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.

14.
Cureus ; 16(5): e60579, 2024 May.
Article in English | MEDLINE | ID: mdl-38894803

ABSTRACT

Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion, potentially leading to cerebral ischemia due to inadequate oxygen and nutrient supply to the brain tissue. The development of collateral vessels in stenotic regions, inherently fragile and prone to rupture, may further precipitate intracerebral hemorrhage. Alongside focal neurological symptoms, the common clinical presentations of Moyamoya angiopathy encompass headaches, dizziness, cognitive impairments, seizures, and involuntary movements. When associated with an underlying systemic illness, including Down Syndrome, cranial radiation, neurofibromatosis type 1, or meningitis, the condition is termed Moyamoya syndrome; whereas when idiopathic and a genetic mutation are identified, it is referred to as Moyamoya disease. In this report, we present a case of the rare Moyamoya syndrome, which was attributed to syphilis and HIV infection and was identified during an investigation into the etiology of ischemic stroke in a young patient.

15.
Cureus ; 16(5): e60697, 2024 May.
Article in English | MEDLINE | ID: mdl-38899257

ABSTRACT

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening condition found in immunocompromised individuals, especially in human immunodeficiency virus (HIV) positive patients. Here, we report a case of PCP in a presumably immunocompetent 25-year-old male patient who presented with a one-month history of chest pain, dyspnea, and a nonproductive cough with recent development of night sweats. The patient recently immigrated to the United States without any known medical or family history. A chest radiograph revealed moderate pneumothorax for which a chest tube was placed. A chest computed tomography (CT) scan revealed diffuse lung disease with multiple thin- and thick-walled cystic lesions on a background of diffuse ground-glass opacities. Based on these radiologic findings and subsequent positive HIV serology, there was a high suspicion of PCP. Bronchoalveolar lavage was performed, and PCR for Pneumocystis jirovecii was positive. Appropriate treatment was initiated, and the patient recovered well. Through this report, we aim to highlight the importance of recognizing the various clinical and radiologic findings of PCP even in patients with no overt risk factors. Prompt and targeted treatment could mitigate morbidity and mortality associated with this opportunistic pathogen.

16.
Viruses ; 16(6)2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38932227

ABSTRACT

The HIV envelope glycoprotein (Env) is a trimeric protein that facilitates viral binding and fusion with target cells. As the sole viral protein on the HIV surface, Env is important both for immune responses to HIV and in vaccine designs. Targeting Env in clinical applications is challenging due to its heavy glycosylation, high genetic variability, conformational camouflage, and its low abundance on virions. Thus, there is a critical need to better understand this protein. Flow virometry (FV) is a useful methodology for phenotyping the virion surface in a high-throughput, single virion manner. To demonstrate the utility of FV to characterize Env, we stained HIV virions with a panel of 85 monoclonal antibodies targeting different regions of Env. A broad range of antibodies yielded robust staining of Env, with V3 antibodies showing the highest quantitative staining. A subset of antibodies tested in parallel on viruses produced in CD4+ T cell lines, HEK293T cells, and primary cells showed that the cellular model of virus production can impact Env detection. Finally, in addition to being able to highlight Env heterogeneity on virions, we show FV can sensitively detect differences in Env conformation when soluble CD4 is added to virions before staining.


Subject(s)
HIV-1 , Virion , env Gene Products, Human Immunodeficiency Virus , Humans , env Gene Products, Human Immunodeficiency Virus/chemistry , env Gene Products, Human Immunodeficiency Virus/metabolism , env Gene Products, Human Immunodeficiency Virus/genetics , env Gene Products, Human Immunodeficiency Virus/immunology , HIV-1/genetics , HIV-1/physiology , HIV-1/immunology , Virion/metabolism , HEK293 Cells , HIV Antibodies/immunology , Antibodies, Monoclonal/immunology , CD4-Positive T-Lymphocytes/virology , CD4-Positive T-Lymphocytes/immunology , HIV Infections/virology
17.
Curr HIV Res ; 2024 06 10.
Article in English | MEDLINE | ID: mdl-38899524

ABSTRACT

INTRODUCTION/OBJECTIVES: Different ART (antiretroviral therapy) options may affect the risk of osteopenia/osteoporosis in people living with HIV (PLWH) having increased life expectancy. Current guidelines recommend bone mineral density (BMD) measurement only in patients at risk. In our study, we investigated the prevalence of osteopenia/osteoporosis and associated risk factors in naive patients not receiving ART. METHODS: This study included 116 newly diagnosed, ART naive HIV-positive patients who were studied retrospectively. Vitamin D level, BMD measurement, CD4 and CD8 count, CD4/CD8 ratio, HIV RNA level, body mass index and other risk parameters of ART naive patients were included in our study. RESULTS: Of 116 patients, 103 were male and 13 female. 47.4% (osteoporosis in 4.3%, osteopenia in 43.1%) of patients had osteopenia/osteoporosis. The patients with osteopenia/osteoporosis had older age (39.2±11.0 vs 32.0±8.6, p=0.0001), lower vitamin D levels (16.0±5.0 vs 24.4±6.3, p=0.0001), lower BMI (body mass index) (23.0±4.0 vs 24.6±4.6 p<0.05), lower CD4 and CD8 counts (405.1±885.0 vs 467.3± 695.1; 849.9570.4 vs 1012.0±629.4 respectively, p<0.05). 41.8% had CD4 count ≤200/µL (vs 18.0%, p=0.005). No statistically significant differences were observed in terms of gender distribution, smoking, alcohol and drug use, comorbidities and, additional drug use and HIV RNA >100 000 copies/ml. In multivariate analysis, age and vitamin D level were significant and independent (p<0.05) risk factors with osteoporosis/osteopenia. CONCLUSION: Being over 40 years of age, CD4 count ≤200/µL, vitamin D level <20 ng/mL and low BMI are the most important risk factors for osteopenia/osteoporosis in ART naive patients. Among these parameters, age and vitamin D level were significant and independent risk factors. These factors may guide the determination of the need for dual-energy x-ray absorptiometry (DXA) testing in ART naive patients and drug choices in the treatment plan.

18.
Arthroplast Today ; 27: 101382, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38872811

ABSTRACT

Background: Total knee arthroplasty (TKA) has become a common surgical intervention for human immunodeficiency virus (HIV)-positive patients who develop osteonecrosis of the knee. This paper summarized existing literature regarding the outcomes of HIV-positive patients undergoing TKA in 4 subsections: (1) complications; (2) survivorship analyses; (3) patient-reported outcomes; and (4) infections. Methods: A review of PubMed was performed, searching for articles focused on HIV-positive patients undergoing TKA. There were 6 reports selected, containing 4765 HIV-positive patients, and data regarding the various domains was tabulated and analyzed. To ensure article quality, a methodology score and level of evidence were determined for selected studies. Results: Complication rates for HIV-positive patients were low, with a larger study reporting that 7.8% of HIV-positive patients developed a complication in comparison to 8% of HIV-negative patients. Survivorship analyses showed similar results, with a study reporting implant survivorship of 98% for HIV-positive and 99% for HIV-negative patients. There were no differences in patient-reported outcomes; HIV-positive patients improved from baseline with respect to the mean Knee Society objective and mean Knee Society functional scores, and the University of California, Los Angeles self-reported activity levels. The infection rate for HIV-positive patients was low, with a larger database study reporting that 0.6% of HIV-positive patients developed a wound infection in comparison to 0.4% of HIV-negative patients. Conclusions: A TKA is an effective treatment for HIV-positive patients who develop osteonecrosis of the knee. Results showed similar patient-reported outcomes, implant survivorships, revisions, and complication rates when compared to non-HIV patients.

19.
Int J Hematol Oncol Stem Cell Res ; 18(2): 206-209, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38868809

ABSTRACT

Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S deficiency, antiphospholipid antibody syndrome, and heightened levels of pro-inflammatory cytokines. This case report highlights an exceptionally uncommon occurrence of deep venous thrombosis in an HIV-infected patient receiving a therapeutic dose of enoxaparin. This underscores the need for cautious consideration of the risk of VTE in HIV-infected individuals, even with preventive or therapeutic anticoagulant treatment. Further research is recommended to investigate HIV as a potential risk factor of prophylactic anticoagulation.

20.
AIDS Behav ; 28(8): 2630-2638, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38856847

ABSTRACT

Globally, Botswana has one of the highest burdens of HIV. This study estimated the impact of the COVID-19 pandemic on the HIV cascade of care in Sub-Saharan Africa. We conducted an interrupted time series analysis on national-level data to estimate the effect of COVID-19 on the numbers of HIV tests, positive HIV tests and ART initiations from April 2019 until March 2021. In multivariable Poisson interrupted time series regression, the COVID-19 lockdown was associated with a 27% decrease in the monthly numbers of HIV tests (IRR 0.73, 95%CI 0.72-0.73), a 25% decrease in HIV positive tests (IRR 0.75, 95%CI 0.71-0.79), and a 43% reduction in ART initiations (IRR 0.57, 95%CI 0.55-0.60). The impact of the pandemic on all three outcomes was worse in males and those aged ≥ 50 years. In conclusion, COVID-19 had a strong negative impact on HIV screening, diagnosis and ART initiation in Botswana.


Subject(s)
COVID-19 , HIV Infections , Interrupted Time Series Analysis , SARS-CoV-2 , Humans , Botswana/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , HIV Infections/epidemiology , Male , Female , Adult , Middle Aged , HIV Testing/statistics & numerical data , Young Adult , Anti-HIV Agents/therapeutic use , Pandemics
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