Current HIV Research最新文献

Background: Valaciclovir, a prodrug of acyclovir, is used to treat herpes simplex virus infections. The pharmacokinetics of the drug, namely, low oral bioavailability and short half-life, demands an alternative drug delivery system. Since the drug normally targets virus-infected cells and is metabolized into active acyclovir, its therapeutic effect can be achieved through both local and systemic action when administered vaginally. The innate physiological characteristics of the vagina limit long-term drug availability in the vaginal region.

Objective: This study aimed to propose a nanoparticle-loaded in situ gel as a drug delivery system to achieve both local and systemic effects of the drug.

Methods: Ionotropic gelation-high-speed homogenization was adopted to prepare xanthan gum nanoparticles, where crosslinking agents consisted of a combination of sodium citrate and aluminum chloride. Design Expert Software V13 was used to screen the formulation and processing variables. The nanoparticles were characterized by particle size, zeta potential, morphology, drug loading, and in vitro drug release. The selected nanoparticles were combined with 20% w/v poloxamer 407 and 2% w/v HPMC to produce an in situ mucoadhesive gel, and ex vivo drug permeation was established.

Results: Drug loading ranged from 79.92±0.11 to 95.52±0.11%. During the 12-hour investigation, drug release was promising. The optimum formula exhibited a zeta potential of -18.6 mV and an average particle size of 117.0 nm. The optimized nanoparticle permeability coefficient was fourfold higher than that of the drug-embedded gel. The in situ gel's adhesion strength (0.784 N) revealed adequate mucoadhesive properties.

Conclusion: Nanoparticulate mucoadhesive gels are a promising approach for the management of genital herpes infection.

Introduction: Co-infections with human cytomegalovirus (HCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Toxoplasma gondii (T. gondii) pose clinical challenges in human immunodeficiency virus-1 (HIV-1)-infected individuals by complicating disease progression and management. This study aimed to investigate the serological and molecular prevalence of HCMV, HBV, HCV, and T. gondii co-infections among treatment-naive HIV-infected individuals.

Methods: A cross-sectional study was conducted from March 2022 to August 2024 on 203 treatment-naive HIV-1-infected individuals. Plasma samples were analyzed using ELISA for serological markers and real-time PCR for molecular detection. Statistical analyses were performed to assess demographic and clinical variables associated with co-infections.

Results: Among the 203 participants, the prevalence of anti-HCV antibodies, HBsAg, HCMV IgM, and T. gondii IgM was 9.9%, 2.5%, 1.5%, and 0.5%, respectively. Molecular detection confirmed active HBV, HCV, and HCMV infections in 40%, 60%, and 66.7% of seropositive individuals, respectively, while T. gondii DNA was undetected. HCV genotyping revealed subtype 1a as the most common (50%), followed by 3a (37.5%) and 1b (12.5%).

Discussion: The findings indicate a moderate prevalence of HBV and HCV co-infections and a low prevalence of HCMV and T. gondii co-infections in treatment-naive HIV patients.

Conclusion: These results highlight the need for targeted public health interventions, including vaccination and screening strategies, to reduce the risk of co-infections in HIV-infected individuals.

Background: 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.

Case presentation: We present a 57-year-old HIV-positive female who developed a brain abscess after discontinuing antiretroviral therapy (ART) in 2019. She presented in 2023 with progressive headaches, fever, and vomiting. MRI revealed a ring-enhancing lesion, suggesting a brain tumor or severe infection. Craniotomy with pus aspiration confirmed Nocardia sp. The patient was treated with trimethoprim/sulfamethoxazole (TMP-SMX) and imipenem-cilastatin, showing sig-nificant improvement after two weeks of intravenous therapy. The patient was then discharged on oral TMP-SMX.

Conclusion: This case highlights the diagnostic challenges of nocardial brain abscesses in pa-tients with HIV and highlights the importance of diagnosis, early neurosurgical intervention, and targeted antimicrobial therapy in improving outcomes.

Introduction: 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.

Material and methods: This retrospective observational study analysed PLHIV who developed anal cancer between 2000 and 2021 at a third-level university hospital. Epidemiological, immunological, and microbiological factors, as well as disease management and outcomes, were assessed.

Results: A total of 38 patients were included, 95% of whom were men, with an incidence rate of 105 cases per 100,000 person-years. The median CD4 nadir was 169 cells/μl, with 60% of patients having a CD4 nadir <200 cells/μl, and 93.3% had a CD4/CD8 ratio <0.4. HPV infection was documented in 100% of tested patients (35/38), and 50% presented with advanced tumor stages. At 2 years post-diagnosis, 66% achieved complete remission, while 13.2% had a recurrence. Long-term tumor-related mortality was 15%, with an overall survival of 66%.

Discussion: A significant number of patients presented with advanced-stage anal cancer and ongoing immunosuppression, emphasising the need for earlier detection and better follow-up. Despite guidelines, screening participation remains low, highlighting the importance of multidisciplinary care and targeted prevention strategies in high-risk PLHIV populations. However, as a retrospective single-centre study with a limited sample size, our findings may be affected by information and selection bias, restricting broader applicability.

Conclusion: Co-infection with HIV and HPV and low CD4 nadir were common features in these patients. HPV prevention and anal dysplasia screening are crucial to reducing this emerging condition.

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.

Introduction: 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.

Methods: We conducted a randomized trial among virologically suppressed PWH aged ≥18 years on TDF + FTC or 3TC + EFV who were switched to either TLD or DTG + 3TC. The primary outcome was the change in estimated glomerular filtration rate (eGFR) calculated by cystatin C at 24 weeks.

Results: Sixteen participants (eight per group), 69% male with a mean age of 41 years and a median duration of HIV diagnosis of 7.1 years, were enrolled. A greater, though not statistically significant, decline in eGFR was observed in the TLD group. The mean differences were 5.15 mL/ min/1.73 m² (95% CI: -12.06 to 22.35; p = 0.532) for cystatin C and 4.01 mL/min/1.73 m² (95% CI: -3.58 to 11.59; p = 0.277) for creatinine. All participants maintained virological suppression. No significant differences were observed in BMI, LDL, or CD4 counts.

Discussion: Although not statistically significant, TLD was associated with a trend toward greater eGFR decline. This finding warrants attention, particularly in patients at risk for renal dysfunction.

Conclusion: Dual therapy with DTG + 3TC may be a preferable switch option over TLD for virologically suppressed PWH with renal safety concerns.

Introduction: 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).

Methods: BCBL-1 cells were initially infected with lentivirus overexpressing HIV-1 Tat. The relative mRNA expression of Farnesyl Diphosphate Farnesyltransferase 1 (FDFT1), HIV-1 Tat, KSHV Open Reading Frame 73 (ORF73), and KSHV Open Reading Frame 50 (ORF50) was quantified by real-time fluorescent quantitative Polymerase Chain Reaction (RT-qPCR). The cellular cholesterol levels were determined using a total cholesterol assay kit. BCBL-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) served as a positive control for the lytic replication of KSHV. The relative mRNA expression levels of HIV-1 Tat, FDFT1, KSHV ORF73, and KSHV ORF50 were subsequently evaluated in BCBL-1 cells following infection with lenti-viruses for FDFT1 overexpression or FDFT1-RNAi knockdown, and the cellular cholesterol content was quantified.

Results: The findings revealed that HIV-1 Tat downregulated FDFT1 and upregulated the expression of KSHV ORF50 in BCBL-1 cells. FDFT1 overexpression upregulated the expression of the latency-associated gene, ORF73, of KSHV in BCBL-1 cells, while knockdown of FDFT1 upregulated the expression of genes associated with the lytic reactivation of KSHV. Infection with the HIV-1 lentivirus, which overexpresses Tat, as well as manipulation of FDFT1, significantly altered the cholesterol content in BCBL-1 cells.

Conclusion: The downregulation of FDFT1 by HIV-1 Tat modulates cellular cholesterol levels and is associated with KSHV replication in BCBL-1 cells.

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.

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.

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.