AIDS research and human retroviruses最新文献

This study aimed to identify key predictors of immunological failure in elderly patients with HIV receiving antiretroviral therapy (ART) through machine learning approaches. We conducted a retrospective analysis of 490 elderly patients with HIV (including 120 with immunological failure) treated at Guigang People's Hospital from January 2009 to May 2024, using data extracted from the AIDS Comprehensive Prevention and Control Information System. Employing a two-stage analytical approach, we first applied least absolute shrinkage and selection operator (LASSO) regression to screen 50 potential risk factors, identifying 6 significant predictors. These were subsequently analyzed via logistic regression, revealing six protective factors: moderate disease stage [odds ratio (OR) = 0.401], AIDS stage (OR = 0.130), cotrimoxazole use (OR = 0.495), β2-microglobulin levels (OR = 0.755), platelet count (OR = 0.767), and alanine aminotransferase levels (OR = 0.760). Age was identified as an independent risk factor (OR = 1.275). Finally, the Shapley Additive explanations (SHAP) algorithm was utilized to rank feature importance, providing interpretable insights into predictor contributions. This study used machine learning (LASSO and logistic regression) to pinpoint critical predictors of immunological failure in elderly patients with HIV on ART, aiding early detection of high-risk individuals and informing prevention strategies.

Liver fibrosis presents a unique diagnostic challenge in people coinfected with hepatitis C virus (HCV) and human immune deficiency virus (HIV). This study aimed to explore the association between CD4 discordance and liver fibrosis in that population, alongside assessing the predictive power of different models for significant fibrosis. A cross-sectional study was conducted on 198 adult people with HIV/HCV coinfection. Liver fibrosis was noninvasively assessed using transient elastography, and CD4 discordance was defined based on the discrepancy between absolute CD4 cell count and CD4 cell percentage. Multivariate logistic regression and receiver operating characteristic curves were used for analysis. Only 52 (26.3%) individuals had concordant CD4 values. The study found a significant correlation between high CD4 discordance and significant liver fibrosis (p < .001), with a higher prevalence of significant fibrosis in those with high discordance (65.5%) than those with low (14.5%) or concordant (13.5%) CD4 values. High CD4 discordance was strongly associated with significant fibrosis (odds ratio = 11.48, p < .001). The CD4-only model showed a high negative predictive value (87.5%), making it suitable for excluding significant fibrosis. In contrast, models incorporating both CD4 count and percentage demonstrated higher positive and negative predictive values (78.6% and 87.6%, respectively), indicating their utility in diagnosing significant fibrosis. This study highlights the complexity of assessing liver fibrosis in HIV/HCV-coinfected individuals and underscores the value of CD4 discordance as a predictive factor. The predictive models, especially those combining CD4 count and percentage, provide an approach for evaluating liver fibrosis. Further research is needed to refine these models and enhance their clinical applicability.

The human T-lymphotropic virus 1 (HTLV-1) affects millions globally, notably in Brazil. The classical neurological presentation of this infection is HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is limited information on its association with lipid disorders and cardiovascular risks. Here, we compare the lipid profile of 30 people with HTLV-1 and HAM/TSP to 73 people with HTLV-1 without evidence of HAM/TSP from a Brazilian reference center between July 2021 and September 2023. People with HAM/TSP had lower levels of high-density lipoprotein and higher levels of low-density lipoprotein (LDL) and total cholesterol than people without HAM/TSP. In addition, people with HAM/TSP had a sixfold risk increase for elevated LDL. Therefore, patients with HAM/TSP show an adverse lipid profile, indicating higher dyslipidemia and cardiovascular risks. Regular lipid monitoring in this group is recommended.

The current HIV-1 epidemic in China is characterized by the co-circulation of multiple subtypes and recombinant forms. A novel circulating recombinant form of HIV-1 (CRF176_BC) has been identified in Yunnan Province, China. Near-full-length genome sequences were obtained from four individuals who identified as heterosexual and were epidemiologically unlinked. Phylogenetic analysis revealed that these sequences formed a distinct monophyletic cluster from known subtypes and CRFs. Bootscanning analyses revealed a subtype C backbone with two subtype B insertions. Bayesian evolutionary dating estimated that the four genomes shared a common ancestor between 2014 and 2016, which was not far from the present. Unlike earlier CRF_BCs, which were associated with injecting drug use in the 1990s, the emergence of CRF176_BC indicates a shift toward sexual transmission. This finding emphasizes the continuous evolution of HIV-1 in Yunnan, driven by co-circulating lineages and evolving transmission dynamics. It also highlights the importance of targeted surveillance in informing public health strategies in the context of evolving epidemics.

The emergence of CRF80_0107 resulted from recombination between co-circulating CRF01_AE and CRF07_BC genotypes. To date, no secondary recombinants involving CRF80_0107 as a parental strain have been documented in public sequence databases. Here, we report the identification and characterization of a novel HIV-1 CRF80_0107/B recombinant form isolated from a treatment-naïve men who have sex with men (MSM) individual in Baoding City, Hebei Province, China. While phylogenetic analysis of the near-full-length genome revealed clustering with the CRF80_0107 lineage, Bootscan and similarity-mapping analyses (RIP 3.0) identified a recombinant structure containing inserted B subtype fragments spanning the env, nef, and 3'LTR regions (HXB2: 7,907-9,342 nt). This represents the first documented CRF80_0107/B strain in the MSM population of northern China, highlighting the need for expanded molecular surveillance to track evolving HIV-1 diversity in this key population.

Studies have shown an association between matrix metalloproteinases (MMPs) along with tissue inhibitors of MMPs (TIMP) and human immunodeficiency virus (HIV) infection and CD4⁺ T cell count, a key clinical indicator for HIV progression, but the causality remains unclear. This study aimed to investigate the bidirectional causal relationship between MMPs/TIMP and HIV. A genome-wide association study-based two-sample bidirectional Mendelian randomization (MR) analysis was conducted to elucidate the potential causal links between MMPs/TIMP and HIV. This approach utilized robust estimators, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode. Furthermore, sensitivity analyses including Cochran's Q, MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO) tests were employed to assess heterogeneity and pleiotropic effects. The IVW analysis in the forward MR study indicated that genetically predicted levels of MMP-3 [odds ratio or OR (95% confidence interval or CI) = 0.69 (0.47-1), p = .047], MMP-20 [OR (95% CI) = 0.64 (0.43-0.97), p = .035], and TIMP-2 [OR (95% CI) = 0.68 (0.47-0.97), p = .034] were potentially associated with a lower risk of HIV. MMP-13 exhibited a genetically predicted association with a higher risk of HIV [OR (95% CI) = 2 (1.17-3.41), p = .011]. Additionally, MMP-19 demonstrated a genetic association with CD4⁺ T cell absolute count [OR (95% CI) = 0.90 (0.81-1.00), p = .042). The reverse MR analysis indicated that genetically predicted liability to HIV was associated with a higher level of MMP-1 [OR (95% CI) = 1.04 (1.01-1.08), p = .024]. Heterogeneity and horizontal pleiotropy were found between MMP-9 and HIV by Cochran's Q test and MR-Egger, but MR-PRESSO indicated no outliers. This study revealed a complex MMPs-TIMPs interplay influencing HIV risk. Future research should clarify underlying mechanisms.

Antiretroviral therapy (ART) has dramatically improved outcomes for people living with HIV (PLWH), yet concerns about cardiovascular disease (CVD) remain, especially in aging populations. In this study, we aimed to evaluate the association between ART regimens and CVD events in Japan using a nationwide pharmacovigilance database. We retrospectively analyzed reports from the Japanese Adverse Drug Event Report Database spanning April 2004 to September 2024. After removing duplicates and records with key missing data, 796,402 reports (Population A) were used for signal detection based on the reporting odds ratio (ROR) and information component (IC). A refined subset (Population B; 2,721 reports) underwent logistic regression to identify risk factors for major adverse cardiovascular events (MACE) and total cardiovascular events (MACE plus angina). ART regimen classes (e.g., integrase strand transfer inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors) and backbone therapies [e.g., abacavir (ABC)/lamivudine] were included in the analysis. Signal detection revealed significant ABC signals in both ROR and IC analyses for MACE and total CVD events. In logistic regression, advanced age (≥70 years), ABC-containing regimens, and diabetes emerged as independent risk factors for MACE and total CVD events. Dyslipidemia and hypertension were not significant in the adjusted models. Our findings underscore a potentially heightened cardiovascular risk associated with ABC, particularly in older PLWH or those with diabetes. These results highlight the need to consider individual CVD risk profiles when selecting ART regimens and reinforce the importance of ongoing pharmacovigilance to guide safer, more personalized treatment strategies worldwide.

Asanté HIV-1 Rapid Recency Assay identifies HIV-1 recent infection based on antibody avidity among newly diagnosed individuals. We estimated the mean duration of recent infection (MDRI), false recency rate (FRR), the probability of being classified as recent over time and examined the assay reproducibility. A total of 967 longitudinal plasma specimens from 180 HIV-1 seroconverting individuals, all antiretroviral treatment (ART) naïve, from multiple countries were used to determine the MDRI, while cross-sectional plasma specimens from individuals infected for >1 year (total n = 1,285; n = 926 without AIDS; n = 359 with AIDS; all ART naïve) were tested to estimate the FRR. All specimens were tested by two testers and results were interpreted visually, followed by a line intensity reader. Linear interpolation and polynomial regression were used to estimate the duration of recent infection by subject. MDRI was calculated as a mean of individual duration of recency while FRR was calculated as a fraction of long-term (LT) cases that were misclassified as recent. The LT line intensity, a reflection of antibody avidity, demonstrated an overall increase over time, especially during the first year after seroconversion. The MDRI was 160 days [95% confidence interval (CI), 140-181] by linear interpolation and 167 days (95% CI, 147-187) by polynomial regression among ART-naïve cases. Probability of individuals testing as recent infection was 97.9% (95% CI, 93.9%-99.3%) by 1 month post-seroconversion and decreased to 10.3% (95% CI, 6.3%-16.5%) by 12 months. FRR was 2.1% (95% CI, 1.3%-3.2%) among ART-naïve individuals infected >1 year and 5.1% (95% CI, 3.4%-7.8%) among patients with AIDS. The assay indicated high inter-tester reproducibility of 96.2%. It can be a valuable tool for program-based HIV-1 recent infection surveillance for a better understanding of risk factors of acquiring new infections. Our study provides evidence about the performance of the assay for data interpretation of recency surveillance among newly diagnosed individuals.

HIV guidelines recommend bone mineral density (BMD) screening by dual-energy x-ray absorptiometry (DXA) for all postmenopausal women and all men ≥50 years, but uptake of these recommendations has been low. We conducted a retrospective cross-sectional analysis of people with HIV (PWH) aged ≥65 or older engaged in routine care to determine DXA completion. We reviewed records of 300 patients (243 men; 57 women). 48% had a DXA scan ordered, and 85% of those with a DXA order had results available within the electronic record. Of those screened, 13% of women and 27% of men had normal BMD; 45% of women and 53% of men had osteopenia; and 42% of women and 20% of men had osteoporosis. Older PWH at the highest fracture risk were under-screened for low BMD, per current HIV guidelines. Improved fracture risk screening is needed for this high-risk patient population.

Acquired immunodeficiency syndrome (AIDS) is a group of disorders caused by the human immunodeficiency virus (HIV). Globally, 1.7 million people became newly infected with HIV in 2019. This study aims to assess trends in HIV burden in India and its states from 1990 to 2019 for tracking the progress of the National AIDS Control Program (NACP). This study assesses the burden of HIV in India and its states from 1990 to 2019, using data on incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) study. The data are presented as age-standardized rates per 100,000 inhabitants, along with corresponding uncertainty intervals (95% UI) and the relative percentage change. Globally, there was a decrease in the age-standardized incidence rate of HIV from 37.59 cases per 100,000 in 1990 to 25.24 cases per 100,000 in 2019. However, in India, it increased from 3.43 cases per 100,000 to 5.01 cases per 100,000 during the same period. There was an increase in both HIV prevalence and HIV-related death rates in India and globally. The increases in estimates were smaller for the rest of the world compared to India. In India, age-standardized incidence, prevalence, mortality, and DALY rates of HIV were reportedly higher in males vis-à-vis females for all years between 1990 and 2019. Age-standardized HIV prevalence, HIV-associated mortality, and DALYs increased globally and in India from 1990 to 2019. Incidence increased in India, while it decreased globally during the same period. To identify bottlenecks in the current NACP recommendations, a multicentric study is needed.