Current HIV Research最新文献

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.

Introduction: Peripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4+/CD8+ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.

Methods: Overall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.

Results: Significant differences in lymphocyte subsets were observed between groups. HIVDLBCL patients showed decreased CD4⁺ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8⁺ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8⁺ T cell counts, reduced CD3⁺ T cell percentages, and elevated CD56⁺CD16⁺ NK cell proportions compared to their younger counterparts.

Discussion: This study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4⁺ T cell depletion and CD8⁺ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of coinfections. Future studies should expand the cohort and integrate multi-omics data to validate these findings.

Conclusion: Patients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4+ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4+ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.

Introduction/objective: To reveal the epidemiology of kidney disease (KD) in people living with HIV (PWLH) and to report the antiretroviral treatment (ART) management in case of kidney disease.

Methods: This multicenter, retrospective observational study identified KD under four categories: acute kidney disease (AKD), chronic kidney disease (CKD), accelerated decline of glomerular filtration rate (GFR > 60 mL/min), and asymptomatic kidney disease indicated by markers of kidney damage. Clinical characteristics and etiological causes of KD in patients were evaluated.

Results: Among 2092 PLWH screened, 131 patients (6.26%) had at least one form of KD. All patients with KD were Caucasian; 112 (84.5%) were male, with a median age of 51 [range 21-80] years. The most common comorbidities were hyperlipidemia (43.5%), diabetes mellitus (33.6%), and hypertension (26.9%). AKD developed in 20 patients (0.95%), CKD in 35 patients (1.67%), accelerated GFR decline in 69 patients (3.29%), and asymptomatic KD in 7 patients (0.33%). Regarding the etiological causes, 39.7% of KD cases were attributed to ART-related nephrotoxicity, 21.4% to HIV-related nephropathy, 19.8% to comorbidity-associated KD, and 6.9% to non-ART drug nephrotoxicity. ART regimen modification was performed in 39 patients (29.6%) with ARTrelated nephropathy. Lamivudine-based ART required fewer treatment changes (9.5%) than tenofovir disoproxil fumarate (38.1%) or tenofovir alafenamide (36.4%) (P = 0.04).

Discussion: ART-related nephrotoxicity and comorbidity-associated kidney diseases are emerging challenges in the epidemiology of KD among PLWH.

Conclusion: Lamivudine-based ART regimens appear to be favorable in cases of KD development, showing a greater likelihood of preserving the initial treatment regimen.