AIDS research and human retroviruses最新文献

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are vital for fetal metabolic programming and immunomodulation. Higher n-6:n-3 ratios, reflecting a proinflammatory eicosanoid profile, are associated with adverse perinatal outcomes. Limited data exist, however, on n-6 and n-3 PUFAs specifically in the context of HIV and pregnancy. Our objective was to assess HIV clinical factors associated with PUFA signatures in pregnant persons with HIV (PWH). In this observational cohort, third trimester plasma PUFA concentrations (six n-6 PUFAs, four n-3 PUFAs) were measured, each as a percent of total fatty acid content, via esterification and gas chromatography in pregnant PWH enrolled from 2009 to 2011 in the Nutrition substudy of the Pediatric HIV/AIDS Cohort Study. PUFA ratios (n-6:n-3) were calculated. Exposures assessed were first/second trimester CD4 count (<200 vs. >200 cells/mm³), HIV RNA viral load (VL) (VL >400 vs. <400 copies/mL), and protease inhibitor (PI) versus non-PI antiretroviral therapy (ART). Linear regression models using generalized estimating equations were fit to assess mean differences and their 95% confidence intervals (CIs) in n-6:n-3 by each exposure, adjusted for potential confounders. Of 264 eligible pregnant PWH, the median age was 27 years, 12% had CD4 counts <200 cells/mm³, and 56% had VL ≥400 copies/mL in the first/second trimesters. PUFA concentrations and ratios were similar by CD4 count and PI exposure. n-3 concentrations were lower in PWH with VL ≥400 versus <400 copies/mL (median 2.8% vs. 3.0%, p < .01, respectively); no differences were observed for n-6 concentrations by VL. In models adjusted for age, education, tobacco use, body mass index, and PI-based ART, n-6:n-3 was higher in those with VL ≥400 copies/mL (mean difference: 1.6; 95% CI: 0.79-2.48, p = .0001). Therefore, PUFA signatures in viremic pregnant PWH reflect a proinflammatory eicosanoid milieu. Future studies should evaluate associations of proinflammatory PUFA signatures with adverse perinatal outcomes in PWH.

The prevalence and control of hypertension (HTN) among people with HIV (PWH) have not been widely studied since the release of newer 2017 ACC/AHA guidelines ("new guidelines"). To address this research gap, we evaluated and compared the prevalence and control of HTN using both 2003 JNC 7 ("old guidelines") and new guidelines. We identified 3,206 PWH with HTN from the DC Cohort study in Washington, DC, between January 2018 and June 2019. We defined HTN using International Classification of Diseases (ICD)-9/-10 diagnosis codes for HTN or ≥2 blood pressure (BP) measurements obtained at least 1 month apart (>139/89 mm Hg per old or >129/79 mm Hg per new guidelines). We defined HTN control based on recent BP (≤129/≤79 mm Hg per new guidelines). We identified socio-demographics, cardiovascular risk factors, and co-morbidities associated with HTN control using multivariable logistic regression [adjusted odds ratio (aOR); 95% confidence interval (CI)]. The prevalence of HTN was 50.9% per old versus 62.2% per new guidelines. Of the 3,206 PWH with HTN, 887 (27.7%) had a recent BP ≤129/≤79 mm Hg, 1,196 (37.3%) had a BP 130-139/80-89 mm Hg, and 1,123 (35.0%) had a BP ≥140/≥90 mm Hg. After adjusting for socio-demographics, cardiovascular risk factors, and co-morbidities, factors associated with HTN control included age 60-69 (vs. <40) years (aOR: 1.42; 95% CI: 1.03-1.98), Hispanic (vs. non-Hispanic Black) race/ethnicity (aOR 1.49; 95% CI: 1.04-2.15), receipt of HIV care at a hospital-based (vs. community-based) clinic (aOR 1.21; 95% CI: 1.00-1.47), being unemployed (aOR 1.42; 95% CI: 1.11-1.83), and diabetes (aOR 1.35; 95% CI: 1.13-1.63). In a large urban cohort of PWH, nearly two-thirds had HTN and less than one-third of those met new guideline criteria. Our data suggest that more aggressive HTN control is warranted among PWH, with additional attention to younger patients and non-Hispanic Black patients.

Long-acting cabotegravir plus rilpivirine has revolutionized the concept of antiretroviral therapy, but as the causes of virological failure and satisfaction can depend on patient background, real-world data are needed. In this single-center study, we reviewed clinical records of people with HIV (PWH) who received injectable cabotegravir plus rilpivirine between June 2022 and January 2023. We assessed virological and safety outcomes, including injection site reactions (ISRs) and changes in serum creatinine and cystatin C. Seventy-four patients were included. There were no virological failures. Approximately 80% of individuals achieved HIV-RNA undetectable in all visits up to 14 months (median 13 months) after switching. Pain upon injection was significantly more common at the rilpivirine injection site, while delayed pain was significantly more common at the cabotegravir injection site. The serum creatinine (mean difference -0.12 mg/dL, p < .0001) and the cystatin C (mean difference -0.077 mg/dL, p < .0001) decreased significantly after switching, and in multivariable regression analysis, baseline characteristics did not affect the decrease in these renal function markers. Long-acting cabotegravir plus rilpivirine showed excellent antiviral efficacy and safety in PWH in Japan. ISRs were characterized differently at the cabotegravir and rilpivirine injection sites. Although cystatin C showed decrease after the regimen switch, further confirmation is needed whether cabotegravir plus rilpivirine can improve renal function.

Strategies to improve the scale-up of antiretroviral therapy (ART) for patients with HIV in Trinidad and Tobago, including the adoption of the "Test and Treat All" policy, have accompanied an increase in the number of patients with pretreatment HIV drug resistance (PDR) in the country. However, the scale of this public health problem is not well established. The objective of this study was to estimate the prevalence of PDR and evaluate its impact on viral suppression among patients with HIV receiving care at a large HIV treatment center in Trinidad and Tobago. We retrospectively analyzed data from the Medical Research Foundation of Trinidad and Tobago of patients newly diagnosed with HIV who had HIV genotyping performed. PDR was defined as having at least one drug-resistant mutation. We assessed the impact of PDR on achieving viral suppression within 12 months of ART initiation, using a Cox extended model. Among 99 patients, 31.3% had PDR to any drug, 29.3% to a non-nucleoside reverse transcriptase inhibitor (NNRTI), 3.0% to a nucleoside reverse transcriptase inhibitor, and 3.0% to a protease inhibitor. Overall, 67.1% of the patients who initiated ART (n = 82) and 66.7% (16/24) of patients with PDR achieved viral suppression within 12 months. We found no significant association between PDR status and achieving viral suppression within 12 months [adjusted hazard ratio: 1.08 (95% confidence interval: 0.57-2.04)]. There is a high prevalence of PDR in Trinidad and Tobago, specifically driven by NNRTI resistance. Although we found no difference in virologic suppression by PDR status, there is an urgent need for an effective HIV response to address the many drivers of virologic failure. Accelerating access to affordable, quality-assured generic dolutegravir and adopting it as the preferred first-line ART therapy are critical.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/μCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-β, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.