Current HIV Research最新文献

Background: Since the first recorded HIV-1 infection in 1998, Jiaxing City has seen increasing HIV infections among men who have sex with men (MSM), necessitating targeted research to understand HIV-1 subtypes and drug resistance patterns to improve prevention and treatment strategies.

Objectives: The study aimed to assess the variety of HIV-1 subtypes, the pre-treatment drug re-sistance (PDR) among MSM in Jiaxing, China, and transmission dynamics of drug-resistant strains. The findings may contribute to the development of targeted HIV prevention and control strategies for the MSM population.

Methods: Plasma samples from all newly reported cases of HIV-1 transmitted through male-to-male sexual contact in Jiaxing City from 2020 to 2022 were retrospectively analyzed. Demo-graphic and epidemiological data were collected. Partial pol gene regions were amplified, se-quenced, and analyzed for drug resistance mutations (DRMs) using the Stanford HIV Drug Re-sistance Database. The Calibrated Population Resistance (CPR) program was utilised to identify Surveillance Drug Resistance Mutation (SDRM). A molecular transmission network was con-structed to investigate the scale of transmitted drug resistance (TDR) strains.

Results: We obtained a total of 298 eligible genetic sequences, revealing a diverse distribution of HIV-1 subtypes, with CRF07_BC, CRF01_AE, and CRF55_01B as the most prevalent. Pretreat-ment DRMs were detected in 91 cases (30.5%), yielding an overall PDR prevalence of 11.0%. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) was most frequent (5.4% each). TDR prevalence reached 7.0%, showing an increasing trend (2020-2022). The molecular network analysis indicated sporadic dissemination of drug-resistant cases rather than large-scale transmission chains.

Conclusion: The convergence of high HIV-1 subtype diversity, elevated PDR prevalence, rising TDR rates, and sporadic resistant strain transmission within MSM networks necessitates the sus-tained resistance surveillance and precision public health interventions.

Objective: This study aims to examine neuroanatomical differences associated with depressive symptoms in people with HIV (PWH) by comparing three groups: depressed PWH (PWH Dep+), non-depressed PWH (PWH Dep-), and HIV-negative controls. The primary goal is to explore specific alterations in brain volume and cortical thickness linked to depressive symp-tomatology in PWH.

Methods: A total of 61 male participants (28 PWH, 33 controls) underwent psychiatric evaluation and high-resolution structural MRI scanning. Voxel-based morphometry (VBM) and cortical thickness analyses were conducted, with age and education considered as covariates. Participants were classified into PWH Dep+ and PWH Dep- based on depression scales.

Results: The PWH Dep+ group exhibited increased gray matter volume in the left anterior cin-gulate cortex and decreased cortical thickness in the left frontal pole compared to controls. In contrast, PWH Dep- participants showed increased cortical thickness in the bilateral postcentral gyrus and posterior cingulate gyrus. Additionally, volume reductions in the middle occipital and middle temporal gyri distinguished PWH Dep+ from PWH Dep-.

Conclusions: Depression in PWH is associated with structural brain changes, particularly in frontal and occipital regions. Although causality cannot be inferred due to the cross-sectional design, these results may enhance our understanding of the neuropathological mechanisms un-derlying depression in PWH. The findings should be interpreted with caution, given the relatively small sample size and the exclusion of female participants.

Introduction: The COVID-19 pandemic caused disruptions in the diagnosis, follow-up and treatment of non-COVID-19 patients due to the burden on the healthcare system. This may lead to missed early diagnosis opportunities in people living with HIV (PLWH). This study aimed to investigate the effects of the COVID-19 pandemic on the demographic characteristics, clinical and laboratory findings, diagnosis, follow-up, and treatment processes of PLWH, and the frequency of opportunistic infections (OIs), AIDS-defining malignancies (ADMs), and late diagnosis (LD).

Methods: Our study was designed as a retrospective cohort study. Individuals over the age of 18 years who were newly diagnosed with HIV infection in our hospital between 2018 and 2023 were included in the study. In this study, 246 PLWH were identified. During the pandemic period, the mean age of PLWH was lower (p=0.025), the use of 2 nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI/r) decreased (p=0.026) and antiretroviral therapy (ART) adherence was higher (p=0.015). LD (48.8% vs. 47.5%) was similar for the two periods, OIs rate (22.6% vs. 18.5%) was lower and ADMs rate (4.8% vs. 6.2%) was higher in the pandemic period.

Results: During the quarantine period, OIs rate (p=0.008) and hospitalization (p=0.002) decreased significantly. Compared to the pre-pandemic period, there was a decrease in primary school graduates (p=0.043) and Centers for Disease Control and Prevention (CDC) category C applicants (p=0.029) and an increase in university graduates (p=0.027) in the quarantine period. After the quarantine period, there was an increase in hospitalization (p=0.002), CDC category C admissions (p=0.021) and ART adherence (p=0.016). Other data were similar for the three periods.

Conclusion: In summary, while the COVID-19 pandemic led to notable changes in patients' characteristics and HIV-related clinical characteristics and treatment, the incidence of LD, OIs and ADMs did not increase significantly. Continued monitoring and adaptation of healthcare services are crucial to managing PLWH effectively in the context of global health crises.

Developing an effective HIV-1 vaccine remains a critical global health challenge, hin-dered by the virus's high genetic diversity, immune evasion strategies, and structural complexity of its Envelope (Env) glycoprotein. Broadly neutralizing antibodies (bNAbs), capable of targeting conserved Env epitopes, offer a promising path for vaccine design. Germline-targeting (GT) strat-egies have emerged as a promising approach to engage naive B cell precursors that have the po-tential to mature into bNAb-producing cells. Advances in GT have enabled the design of immu-nogens capable of recruiting specific bNAb precursors in animal models and early clinical trials. Despite these successes, achieving neutralization breadth requires sequential immunizations with tailored boosting strategies to guide B cell maturation. Studies underscore the importance of using immunogens that mimic native Env structures while modulating glycosylation patterns to focus immune responses. Emerging approaches, such as membrane-bound presentation and mRNA de-livery, hold the potential for enhancing immunogen effectiveness and rapid pre-clinical and in human screening to identify combinations of immunogens that foster bNAb lineages. This review seeks to synthesize key developments in GT strategies for HIV-1 vaccines, highlighting the de-sign and implementation of immunogens that drive bNAb precursor maturation. It aims to under-score the importance of integrating structural insights, immunogen sequence design, and delivery methods to enhance the induction of bNAbs, offering direction for future research to address ex-isting gaps and optimize vaccine efficacy.

Objective: Patients living with HIV (PLHIV) have a higher cardiovascular risk than others, which is why the early detection of atherosclerosis in this population is important. The present study reports predictive models of subclinical atherosclerosis for this population of patients, made up of variables that are easily collected in the clinic.

Methods: The study design is a cross-sectional observational study. PLHIV without established cardiovascular disease were recruited for this study. Predictive models of subclinical atherosclerosis (Doppler ultrasound) were developed by testing sociodemographic variables, pathological history, data related to HIV infection, laboratory parameters, and capillaroscopy as potential predictors. Logistic regression with internal validation (bootstrapping) and machine learning techniques were used to develop the models.

Results: Data from 96 HIV patients were analysed, 19 (19.8%) of whom had subclinical atherosclerosis. The predictors that went into both machine learning models and the regression model were hypertension, dyslipidaemia, protease inhibitors, triglycerides, fibrinogen, and alkaline phosphatase. Age and C-reactive protein were also part of the machine learning models. The logistic regression model had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.84-0.99), which became 0.80 after internal validation by bootstrapping. The ma-chine learning techniques produced models with AUCs ranging from 0.73 to 0.86.

Conclusion: We report predictive models for subclinical atherosclerosis in PLHIV, demonstrating relevant predictive performance based on easily accessible parameters, making them potentially useful as a screening tool. However, given the study's limitations-primarily the sample size-external validation in larger cohorts is warranted.

Despite recent advances in other prevention strategies, an effective vaccine is still needed to guarantee a sustained end to the HIV/AIDS pandemic. However, the traditional ap-proaches of vaccinology have thus far failed to produce an effective vaccine. More basic research may be needed to enhance our understanding of HIV immunity and the immunological principles behind vaccination and to leverage advanced technologies before applied research activities can be successfully used to develop a distributable HIV vaccine. US Government funding plays a crucial role in promoting, enabling, and advising independent scientists and experts to perform such research. This article was written to provide, to the broader scientific community, detail about the tools NIAID uses for research funding, how and why they were used for HIV vaccine development, and how they have been helpful; it is written from the perspective of a Program Officer's experiences while working for more than 25 years in the Division of AIDS (DAIDS) of NIAID at the NIH (the US National Institutes of Health). Several types of funding activities pro-mote HIV vaccine development efforts, but three types of such activities and their impact on HIV vaccine development will be discussed in more detail.

Introduction: The effectiveness of antiretroviral therapy (ART) in treating HIV is in-fluenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.

Methods: In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing viro-logical failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and re-sistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) ac-cording to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.

Results: Genotyping of plasma samples revealed that a significant proportion of patients exhib-ited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indica-tors, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment re-sponse. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to trans-mission risk factors were also found to be linked to resistance levels, underscoring the multifac-torial nature of resistance development.

Conclusion: Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.

Introduction: The enduring presence of HIV reservoirs represents an important obsta-cle to clinical management. Extensive research has been conducted in this field, but there are no bibliometric analyses focusing on HIV reservoir research.

Aim: This study aimed to present the current status and global trends in HIV reservoir research through bibliometric analysis.

Methods: Studies on HIV reservoirs published from 1 January 1994 to 31 December 2023 were included in the Web of Science Core Collection database, and annual publication numbers, insti-tutions, countries, and authors were analysed using CiteSpace bibliometric software. Further-more, popular research topics and trends were analysed using co-cited references and keywords. From 1994 to 2023, 5778 publications on HIV reservoirs were included, with the United States producing the most publications, citations, and research funding. The most productive individual author was Nicolas Chomont. Cell was the journal publishing the most publications, while Nat Med had the best total link strength. The University of California System was the institution that made the greatest contribution. Keyword clustering analysis of the extracted publications indi-cated that the research areas over the past three decades have primarily focused on "central nerv-ous system," "histone deacetylase," "multiple Epstein‒Barr virus infection," and "dendritic cell."

Results: Moreover, keyword emergence analysis indicates that "provirus" and "identification" are likely to become central themes in future research. Future investigations should prioritize elucidating the specific mechanisms underlying proviral persistence and the identification of novel biomarkers in HIV reservoirs. Additionally, exploring the role of proviral dynamics in ther-apeutic development and reservoir targeting could offer new insights into potential treatment strategies.

Conclusion: This study makes a significant contribution to the understanding of HIV reservoirs, shedding light on key characteristics and emerging trends while also pointing to future research directions.

This article discusses how the RV144 Phase 3 HIV-1 vaccine trial conducted over 15years ago impacted the subsequent direction of research intended to create and evaluate vaccineswith potentially greater efficacy. Follow-on Phase 2b and Phase 3 trials directly or indirectlyinspired by the modest efficacy reported for the RV144 trial have not shown any significantprotection against HIV-1 acquisition. No credibly protective new immunogens have emergedfrom the Correlates of Protection (CoP) or Risk (CoR) analyses conducted after RV144-inspiredstudies in either humans or various macaque models. Notably, the RV144 trial did not induceneutralizing antibodies (NAbs), only non-NAbs. However, only NAbs have been shown to beprotective in macaque models. One possible but underappreciated explanation for the outcome ofthe RV144 trial could be trained innate immune responses against the non-HIV-1 canarypox virusvector antigens, considering the placebo group only received saline. In this article, the authoroutlines how monkey model research based directly or indirectly on the RV144 trial could stillyield useful information on the possible role of trained immunity in short-term vaccine protection.However, non-human primate research, in general, should now focus on testing new immunogensthat have a reasonable chance of inducing NAbs in humans, rather than expending more resourceson CoP/CoR studies inspired by the RV144 trial and its follow-ups.