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1.
Curr HIV Res ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39279712

RESUMEN

INTRODUCTION: The C-C chemokine receptor type 5 (CCR5) is a major co-receptor for human immunodeficiency virus (HIV). Some individuals carry the CCR5 delta-32 genetic polymorphism. People with homozygous CCR5 delta-32 gene are nearly completely resistant to HIV-1 infection. High-resolution melting curve (HRM) analysis is a post-PCR technique utilized for identifying genetic variations in a quick, affordable, and closed-tube assay. The objective of this study was to develop an HRM assay for easy detection of delta-32 mutations. MATERIALS AND METHODS: DNA was extracted from peripheral blood mononuclear cells. HRM was performed to detect delta-32 mutation. The study investigated the impact of various factors, including annealing temperature, template concentration, touchdown PCR, additives, amplicon size, and program settings, on HRM Tm differentiation. RESULTS: It was expected that there would be a 4°C Tm difference between amplicons with and without delta-32 mutation, but the test showed a difference of only 2.3°C. In attempts to identify heterozygote delta-32 variants, a Tm difference of only 0.4°C could be achieved. Various modifications were applied, such as adjusting the template concentration, using touchdown PCR, and adding DMSO and glycerol. However, none of these changes helped to differentiate the Tm effectively, especially in delta-32 heterozygote samples. CONCLUSION: The HRM test identified four samples with heterozygote mutations in each HIV-infected (8.89%) and control (5.72%) groups. More importantly, this study showed that identifying the delta-32 mutation of the CCR5 gene using HRM assay is not as straightforward as previously suggested in some literature, and it requires special setup conditions.

2.
Biomolecules ; 14(9)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39334852

RESUMEN

The binding of the HIV-1 Gag polyprotein to the plasma membrane is a critical step in viral replication. The association with membranes depends on the lipid composition, but its mechanisms remain unclear. Here, we report the binding of non-myristoylated Gag to lipid membranes of different lipid compositions to dissect the influence of each component. We tested the contribution of phosphatidylserine, PI(4,5)P2, and cholesterol to membrane charge density and Gag affinity to membranes. Taking into account the influence of the membrane surface potential, we quantitatively characterized the adsorption of the protein onto model lipid membranes. The obtained Gag binding constants appeared to be the same regardless of the membrane charge. Furthermore, Gag adsorbed on uncharged membranes, suggesting a contribution of hydrophobic forces to the protein-lipid interaction. Charge-charge interactions resulted in an increase in protein concentration near the membrane surface. Lipid-specific interactions were observed in the presence of cholesterol, resulting in a two-fold increase in binding constants. The combination of cholesterol with PI(4,5)P2 showed cooperative effects on protein adsorption. Thus, we suggest that the affinity of Gag to lipid membranes results from a combination of electrostatic attraction to acidic lipids, providing different protein concentrations near the membrane surface, and specific hydrophobic interactions.


Asunto(s)
Colesterol , VIH-1 , Productos del Gen gag del Virus de la Inmunodeficiencia Humana , VIH-1/metabolismo , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química , Colesterol/metabolismo , Colesterol/química , Unión Proteica , Lípidos de la Membrana/metabolismo , Lípidos de la Membrana/química , Membrana Celular/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Adsorción , Membrana Dobles de Lípidos/metabolismo , Membrana Dobles de Lípidos/química , Propiedades de Superficie , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfatidilinositol 4,5-Difosfato/química , Fosfatidilserinas/metabolismo , Fosfatidilserinas/química , Humanos
3.
medRxiv ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39228723

RESUMEN

Background: 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. Methods: 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. Discussion: 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. Trial Registration: ClinicalTrials.gov identifier: NCT06165614.

4.
Front Public Health ; 12: 1394842, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296834

RESUMEN

Background: Urinary tract infections (UTIs) and antibacterial resistance (ABR) are important public health problems, but they are not well-studied among people living with human immunodeficiency virus (PLHIV) globally, especially in low-income countries. Therefore, it is important to regularly measure the extent of UTIs and ABR in the most susceptible populations. This study aimed to investigate the prevalence of UTIs, associated factors, bacterial causal agents, and their antibiotic susceptibility profile among PLHIV in central Ethiopia. Methods: A hospital-based cross-sectional study was conducted to recruit 688 PLHIV by a simple random sampling method. Background information was gathered through interviews, while clinical information was gathered from recent information sheets of patient charts using organized, pretested, and validated study tools. Midstream urine was collected aseptically and transported to the Microbiology Laboratory of Aklilu Lemma Institute of Pathobiology within 4 h of collection, maintaining its cold chain. Standard conventional microbial culture methods and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry were used to identify the bacterial isolates at the species level. Kirby Bauer's disk diffusion method was used to determine the antibiotic susceptibility profile of the bacterial isolates based on the interpretation guidelines of the Clinical Laboratory Standard Institute. Logistic regression models were used to examine factors associated with the occurrence of UTIs among PLHIV attending selected hospitals in Addis Ababa, and Adama. Results: Out of 688 PLHIVs involved in the current study, 144 (20.9%) were positive for UTIs, whereas the majority were asymptomatic for UTIs. In the multivariable logistic regression analysis, only HIV RNA ≥ 200 copies/ml [AOR = 12.24 (95% CI, 3.24, 46.20), p < 0.01] and being symptomatic for UTIs during the study period [AOR = 11.57 (95% CI, 5.83, 22.97), p < 0.01] were associated with the occurrence of UTIs. The dominant bacterial species isolated were Escherichia coli (E. coli; n = 65; 43%), followed by Enterococcus faecalis (E. faecalis; n = 16; 10.6%) and Klebsiella pneumoniae (K. pneumoniae; n = 11; 7.3%). Over half of the E. coli isolates were resistant to antibiotics such as gentamicin (GM; n = 44; 67.7%), amikacin (AN; n = 46; 70.8%), nalidixic acid (NA; n = 42; 64.6%), ciprofloxacin (CIP; n = 40; 61.5%), and azithromycin (AZM; n = 45; 69.2%). All of the K. pneumoniae isolates (n = 11; 100%), (n = 6; 54.5%), and (n = 7; 63.6%) were resistant to [amoxicillin as well as amoxicillin + clavulanic acid], ceftriaxone, and sulfamethoxazole + trimethoprim, respectively. All the Staphylococcus aureus (S. aureus) isolates were resistant to cefoxitin, which implies methicillin-resistant S. aureus (MRSA). Conclusion: The high prevalence of UTIs and antibiotic resistance revealed in the current study needs public health interventions such as educating the population about preventive measures and the importance of early treatment of UTIs. Our findings also highlight the need to provide UTI screening services for PLHIV, and healthcare providers should adopt antibiotic stewardship programs to promote and ensure their appropriate and judicious use.


Asunto(s)
Antibacterianos , Infecciones por VIH , Infecciones Urinarias , Humanos , Etiopía/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiología , Masculino , Estudios Transversales , Femenino , Adulto , Prevalencia , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Adolescente , Factores de Riesgo , Hospitales/estadística & datos numéricos , Adulto Joven , Farmacorresistencia Bacteriana
5.
Cureus ; 16(8): e66840, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280565

RESUMEN

Cat-scratch disease (CSD), caused by Bartonella henselae (B. henselae), typically presents with regional lymphadenopathy following a cat scratch or bite. We report a case of a 50-year-old man with a complex medical history including HIV, Crohn's disease, coronary artery disease, and bipolar disorder, who presented with progressively enlarging cervical lymphadenopathy associated with fever, night sweats, and myalgias. Initial evaluation suggested a neoplastic etiology, prompting extensive laboratory investigations and imaging. However, subsequent history prompted serological testing and markedly elevated Bartonella antibody titers, leading to a clinical diagnosis of CSD. Empirical doxycycline therapy was initiated, resulting in the complete resolution of symptoms. This case underscores the importance of considering CSD in the differential diagnosis of lymphadenopathy, particularly in people living with HIV regardless of immunocompetency, and highlights the challenges of diagnosis and management in complex patients.

7.
Respir Med Case Rep ; 52: 102111, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39328403

RESUMEN

Central airway obstruction (CAO) is generally defined as airflow limitation due to >50 % occlusion and is most commonly due to malignant etiologies. However, benign etiologies, including herpes-simplex-virus (HSV) endobronchial pseudotumor, can occur. Due to the rarity of HSV causing airway obstruction, an evidence-based approach to the bronchoscopic resection and standardization of therapy after removal are lacking. Herein, we present a case of HSV pseudotumor successfully managed by argon-plasma-coagulation (APC) debulking via bronchoscopy and medical management with intravenous foscarnet due to failed treatment with acyclovir for previous HSV lesions.

8.
Aten Primaria ; 57(1): 103048, 2024 Sep 13.
Artículo en Español | MEDLINE | ID: mdl-39276681

RESUMEN

Routinely obtaining a sexual history is a necessary first step to identify which patients have specific sexual behaviours that may put them at risk and use appropriate protective measures, especially in vulnerable populations. However, late diagnosis of HIV infection remains very high. Combination prevention strategies based on condom promotion, harm reduction programs for people who inject drugs plus PrEP and HIV PEP are the best options to prevent new infections. Screening for STIs (including hepatotropic viruses) and early diagnosis and treatment are essential for the person since it improves the prognosis and complications and also for the community because it breaks the chain of transmission. People living with HIV who have an undetectable viral load do not transmit the virus sexually (undetectable=untransmittable).

9.
Int J Infect Dis ; : 107248, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39341421

RESUMEN

BACKGROUND: The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection. METHODS: We enrolled 628 consecutive children aged ≤ 15 years, admitted for TB suspicion. Multiple cytokines levels in QuantiFERON Gold In-Tube supernatants and antigen 85B antibodies (Ag85B Abs) were assessed in children tested positive with either Xpert TB or mycobacterial culture. Results were compared to control children. FINDINGS: Among the biomarkers most strongly associated with TB, Random Forest Classification analysis selected Ag85B Abs, IL2/IFN-γ ratio, and MIG for the scoring system. The ROC curve derived from our scoring system showed an AUC of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71-97% and specificity 79-99%. INTERPRETATION: This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of the HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system.

10.
Biomedicines ; 12(9)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39335448

RESUMEN

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus and neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion and neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces HIV-1, CATB secretion, and neuronal apoptosis. We aimed to elucidate the intracellular pathways modulated by BD1047 in HIV-infected MDM exposed to cocaine. We hypothesized that the Sig1R antagonist BD1047, prior to cocaine, significantly deregulates proteins and pathways involved in HIV-1 replication and CATB secretion that lead to neurotoxicity. MDM culture lysates from HIV-1-infected women treated with BD1047 before cocaine were compared with untreated controls using TMT quantitative proteomics, bioinformatics, Lima statistics, and pathway analyses. Results demonstrate that pretreatment with BD1047 before cocaine dysregulated eighty (80) proteins when compared with the infected cocaine group. We found fifteen (15) proteins related to HIV-1 infection, CATB, and mitochondrial function. Upregulated proteins were related to oxidative phosphorylation (SLC25A-31), mitochondria (ATP5PD), ion transport (VDAC2-3), endoplasmic reticulum transport (PHB, TMED10, CANX), and cytoskeleton remodeling (TUB1A-C, ANXA1). BD1047 treatment protects HIV-1-infected MDM exposed to cocaine by upregulating proteins that reduce mitochondrial damage, ER transport, and exocytosis associated with CATB-induced neurotoxicity.

11.
J Theor Biol ; 594: 111914, 2024 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-39111541

RESUMEN

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.


Asunto(s)
Aprendizaje Profundo , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Algoritmos , Fármacos Anti-VIH/uso terapéutico , Simulación por Computador , Esquema de Medicación
12.
Cureus ; 16(7): e64304, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130838

RESUMEN

Thrombotic microangiopathy (TMA) is a condition characterized by hemolytic anemia, thrombocytopenia, and organ damage due to the formation of microthrombi. It can be classified as primary or secondary, with secondary TMA being associated with conditions such as infections, autoimmune diseases, and malignancies. This report details the case of a 39-year-old male with secondary TMA, exploring the potential roles of malignant hypertension and HIV infection with the aim of examining the potential link between malignant hypertension and HIV infection in the development of TMA, highlighting the need for a thorough and broad diagnostic approach.

13.
Front Cell Dev Biol ; 12: 1372573, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086659

RESUMEN

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.

14.
Cureus ; 16(7): e64860, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39156471

RESUMEN

Herpes simplex virus (HSV) frequently affects the ocular and genital regions, especially in immunocompromised individuals. On rare occasions, HSV infections can present as pseudotumors. These pseudotumors may mimic cancerous growths, condylomas, or hypertrophic lesions rather than the characteristic small ulcerations. The development of pseudotumors due to HSV is particularly uncommon, especially in the facial region. This atypical presentation poses significant diagnostic challenges and may potentially lead to erroneous identification as a cancerous growth. This case report details a 53-year-old African American man with human immunodeficiency virus (HIV) (noncompliant with antiretroviral therapy) presenting with a purulent ocular pseudotumor secondary to HSV infection, along with a review of the literature surrounding HSV pseudotumors.

15.
Viruses ; 16(8)2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39205255

RESUMEN

Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell's susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of the HIV-1 replication cycle, contributing to productive infection and replication, or severely attenuating the chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to the various HIV-1 target cell types where appropriate.


Asunto(s)
Infecciones por VIH , VIH-1 , Interacciones Huésped-Patógeno , Replicación Viral , VIH-1/fisiología , Humanos , Infecciones por VIH/virología
16.
Microorganisms ; 12(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39065058

RESUMEN

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.

17.
J Clin Immunol ; 44(7): 163, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008214

RESUMEN

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.


Asunto(s)
Anticuerpos Neutralizantes , Autoanticuerpos , Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Masculino , Colombia , Femenino , Adulto , Cryptococcus gattii/inmunología , Persona de Mediana Edad , Cryptococcus neoformans/inmunología , Criptococosis/inmunología , Criptococosis/diagnóstico , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Estudios Retrospectivos , Seronegatividad para VIH/inmunología , Adulto Joven , Anciano
18.
Med Sci (Basel) ; 12(3)2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39051379

RESUMEN

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.


Asunto(s)
Terapia Genética , Infecciones por VIH , Humanos , Tratamiento Basado en Trasplante de Células y Tejidos , Replicación Viral , VIH
19.
Cureus ; 16(6): e61562, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38962632

RESUMEN

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.

20.
Front Public Health ; 12: 1366795, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962784

RESUMEN

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.


Asunto(s)
Infecciones por VIH , Sífilis , Carga Viral , Humanos , Sífilis/epidemiología , Estudios Transversales , Masculino , Adulto , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Femenino , China/epidemiología , Persona de Mediana Edad , Factores de Riesgo
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