AIDS research and human retroviruses最新文献

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.

Yunnan Province is one of the provinces in China severely affected by HIV-1. To track the evolution and epidemiological characteristics of HIV-1 genetics in Yunnan Province, this study conducted a retrospective molecular epidemiological study of HIV-1 in new infections in Yunnan Province. From the newly reported HIV-infected individuals throughout Yunnan Province from January to March 2018, cases with CD4⁺ T lymphocytes less than 200 cells/µL were excluded for BED capture enzyme immunoassay (BED-CEIA). Samples identified as recent infections by BED-CEIA were subjected to viral gene amplification to analyze the distribution characteristics of HIV-1 genotypes and the prevalence of pretreatment resistance. Of the 1,740 samples tested by BED-CEIA, 448 were identified as newly infected, and 323 were successfully genotyped; 14 HIV-1 genotypes were identified, including 2 subtypes, 11 circulating recombinant forms (CRFs), and several unique recombinant forms (URFs), of which CRF08_BC (37. 5%, 121/323), CRF07_BC (22.6%, 73/323), URFs (18.3%, 59/323), and CRF01_AE (14.9%, 48/323) were the predominant genotypes. CRF08_BC had higher proportions in the northeastern, southeastern, central, and southwestern regions of Yunnan Province than in the northwestern region and was more common in the 40-49-year age group, married, and heterosexual contacts. CRF01_AE had significantly higher proportions in the southeastern and northwestern regions and among those with homosexual contact, whereas no significant correlations were found for CRF07_BC and URFs. The overall prevalence of pretreatment resistance was 8.5% [95% confidence interval (CI): 5.5%-12.4%], with the highest proportion of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs; 6.0%, 95% CI: 3.5%-9.4%). This study demonstrated the genetic diversity and regional and subpopulation distribution characteristics of the recently infected HIV-1 population in Yunnan Province, and that pretreatment resistance was at a moderate level, but resistance to NNRTIs needs attention. This study provided the baseline data for a systematic study of the evolution of HIV-1 genetics in a typical endemic area.

The advances in antiretroviral therapy (ART) bring forth an ever-growing percentage of aging people living with HIV (PLHIV) with successful immune restoration (SIR) but increased comorbidities and reduced quality of life. The current criteria for SIR, CD4 absolute count (AC) >500 cells/µL, are proving not to be sufficiently informative enough for preventing or monitoring these unwelcome changes. Messenger RNA (mRNA) of genes, such as CXCL8, IL-6, and CSF-2, that have shown relations with HIV/HIV-associated comorbidities could represent early indicators of increase in viral load and/or pathological changes leading development of comorbidities. Our results display an underexpression of CXCL8 and IL-6 in ART+ PLHIV with CD4 AC >1,000, but not with CD4 AC <1,000, compared to ART-PLHIV and lower levels of CSF-2 mRNA in ART+ CD4 AC >1,000 compared to ART+ CD4 AC <1,000. Taken together, these findings indicate the need to stratify and expand HIV monitoring beyond CD4 AC >500.

HIV cure research has advanced, utilizing analytical treatment interruption (ATI) as a research tool alongside therapeutic strategies such as latency-reversing agents, block and lock strategies, immune-based therapies, cell and gene therapies, and combination approaches to overcome viral persistence. While promising, participation in cure trials remains limited, particularly for long-term survivors (LTS) who have lived with HIV for decades. Many LTS are willing to participate but face barriers such as age-based exclusions, comorbidities, and trial design constraints. With over half of the people with HIV in the United States aged 50 or older, addressing these barriers is crucial to designing inclusive, equitable, and representative cure trials. We conducted 32 semi-structured interviews with LTS of HIV, aged 60 years and older, recruited through community-based organizations and research networks across the United States. Participants were diverse in age, sex, gender, race, and ethnicity. We transcribed, anonymized, and analyzed interviews thematically. Most participants expressed a willingness to participate in HIV cure research, driven by a sense of responsibility and hope for future generations. However, concerns were raised about age-based exclusions from HIV cure trials, which many participants viewed as unjust given their long-term experience with HIV and commitment to finding a cure that could potentially benefit people of their age. Additional concerns included the risks of ATIs, such as viral rebound and the development of viral resistance, along with logistical challenges, including transportation and invasiveness of certain procedures. Despite these barriers, most LTS indicated they would participate in HIV cure trials if researchers addressed their concerns about safety, accessibility, and inclusion. LTS emphasized the need for transparent communication, clear informed consent, and flexible trial designs that accommodate their needs. By addressing these concerns, researchers can engage LTS more meaningfully in HIV cure research, enriching the field and promoting more inclusive and ethical study designs.

Persons with HIV (PWH) have disproportionate hepatitis C virus (HCV) infection prevalence and liver-related morbidity and mortality. These sequelae may be alleviated by curative direct-acting antiviral (DAA) treatment; however, longitudinal effects of DAAs on clinical biomarkers are not well-characterized. We included PWH enrolled in the HIV Outpatient Study (HOPS) who were prescribed DAAs and DAA-naïve PWH of comparable age, sex, race/ethnicity, and fibrosis-4 (FIB-4) profiles. We contrasted the DAA effect on longitudinal trajectories of immunological and hepatic markers using generalized linear mixed models (GLMM) from 2010 to 2020. Of 347 PWH/HCV coinfection, median age was 53.8 years, 30.5% were women, 67.1% were publicly insured, 44.4% were non-Hispanic Black, and 153 (44.1%) were prescribed DAAs (median follow-up = 3.55 years). In multivariable GLMM analysis, DAA treatment was associated with [mean (95% confidence interval)] faster decline in alanine aminotransferase of -7.86 mu/µL/year (-15.39, -0.33) and faster increase in platelets of 6.99 mu/µL/year (2.89, 11.09). Changes in aspartate aminotransferase were comparable between groups. FIB-4 decreased in the DAA-treated but not the DAA-naïve group: -0.26 (-0.41, -0.11) versus 0.02 (-0.16, 0.20)/year, respectively. There was a faster increase in cluster of differentiation (CD)4 count of 0.05 (0.03-0.08) and CD8 count of 0.04 (0.02-0.07) log cells/mL/year in the DAA-treated compared with the DAA-naïve group (p < .001), but not in the CD4/CD8 ratio (p = .36). Among U.S. PWH/HCV coinfection treated with DAAs, we found modest changes in immunological markers and substantial improvements in hepatic markers modeled over 4 years of DAA treatment. Curative DAA treatment is critical to mitigate advanced liver fibrosis.