AIDS research and human retroviruses最新文献

Despite care and the availability of effective antiretroviral treatment, some human immunodeficiency virus (HIV)-infected individuals suffer from neurocognitive disorders associated with HIV (HAND) that significantly affect their quality of life. The different types of HAND can be divided into asymptomatic neurocognitive impairment, mild neurocognitive disorder, and the most severe form known as HIV-associated dementia. Little is known about the mechanisms of HAND, but it is thought to be related to infection of astrocytes, microglial cells, and macrophages in the human brain. The formation of a viral reservoir that lies dormant as a provirus in resting CD4⁺ T lymphocytes and in refuge tissues such as the brain contributes significantly to HIV eradication. In recent years, a new set of tools have emerged: the gene editing based on the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system, which can alter genome segments by insertion, deletion, and replacement and has great therapeutic potential. This technology has been used in research to treat HIV and appears to offer hope for a possible cure for HIV infection and perhaps prevention of HAND. This approach has the potential to directly impact the quality of life of HIV-infected individuals, which is a very important topic to be known and discussed.

It was confirmed that the sterile alpha motif and HD domain 1 (SAMHD1) limits human immunodeficiency virus type 1 (HIV-1) replication. In contrast, viral protein x (Vpx) in HIV-2 and some simian immunodeficiency viruses can counteract this effect. The possible interaction between SAMHD1 and Vpx was suggested by previous studies; however, there are no data to confirm this interaction. Therefore, this study aimed to study the interaction between two proteins and the properties of Vpx protein for the first time using bioinformatic tools. Vpx and SAMHD1 sequences were obtained from the National Center for Biotechnology Information GenBank. Several software were used to define Vpx properties and the interaction between Vpx and different SAMHD1 isoforms. Our findings indicated the difference in interaction sites among different Vpx. However, in all Vpx proteins, this region is from amino acids 4 to 90. In addition, two regions (26-31 and 134-139) and two amino acids 425 and 429 in SAMHD1 are vital in the possible interaction. In addition, our analysis determined the physicochemical and immunological properties of the Vpx. Considering all factors, this study could confirm that Vpx interacts with SAMHD1, which could inhibit SAMHD1. Moreover, our findings can pave the way for future studies to express and purify Vpx in the laboratory and study this protein in vitro.

The purpose of this study was to evaluate the relationship between intracellular islatravir-triphosphate (ISL-TP) in paired peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS). Three pig-tailed macaques (PMs) were dosed with a single intravaginal extended-release ISL-etonogestrel film for a period of 31 days. After extraction and quantification, repeated measures correlation (r_rm) was assessed between log-transformed DBS and PBMC ISL-TP concentrations. Twenty-six paired PBMC/DBS samples were included. Peak ISL-TP concentrations in DBS ranged from 262 to 913 fmol/punches, PBMC C_max ranged from 427 to 857 fmol/10⁶ cells. Repeated measures correlation yielded an r_rm value of 0.96 (95% confidence interval 0.92-0.98; p < .0001). Importantly, ISL-TP was quantifiable in DBS and its pharmacokinetics were similar to PBMC in PMs. Human studies should evaluate DBS applications in clinical pharmacokinetic studies to help define ISL's place in the antiretroviral drug armamentarium.

The unique recombinant form (URF) of HIV is formed by multiple subtypes which are cocirculating in some area, and the number of HIV recombinants is on the increase worldwide. In this study, we identified a URF named 2019638, composed of CRF01_AE and subtype B, in a man who has sex with men in Qinhuangdao, Hebei province, China. The near-full-length genome (NFLG) sequence was confirmed to be a novel URF. Within this NFLG, two CRF01_AE fragments were inserted into the pol and vif regions, respectively, using subtype B as the backbone. Moreover, the presence of the V106M and V179D point mutations in the reverse transcriptase (RT) region rendered the high-level resistance to efavirenz and nevirapine and intermediate resistance to doravirine. Our findings suggest that the HIV epidemic is evolving toward a high degree of recombination, and we need to continuously monitor HIV genetic diversity to control the further development of the AIDS epidemic.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996.

Detection of drug resistance mutations (DRMs) and HIV-1 subtypes ensures effective therapeutic management for HIV-infected individuals. In Gabon, data on DRMs are very little available in the population of people living with HIV and also among voluntary HIV-positive blood donors. This study aimed to study subtypes and DRMs in HIV-1-positive volunteer blood donors in Gabon. A cross-sectional study was carried out at the National Blood Transfusion Center of Gabon. A purposive sampling method was used to collect 128 HIV-1 seropositive blood samples. Viral RNA was extracted on real-time PCR (Abbott 2000^®), and sequencing was performed on ABI 3500 (Hitachi^®). SPSS version 21.0 software was used for statistical analysis. Of the 128 seropositive volunteer donors included, men and the 29-39-age group were more representative at 78.9% and 49.2%, respectively. Eighty-two samples were sequenced. The majority strains identified were subtype A, subtype F, subtype G, CRF02_AG, and CRF45_cpx. The resistance mutations identified were K103N, L210W, E138G, V179D, V179T, and M46L. The prevalence of resistant subtypes was 25.6%. CRF02_AG strains exhibited high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including efavirenz and nevirapine. The study identified major DRMs in reverse transcriptase and protease that confer high-level resistance to most NNRTIs, nucleoside reverse transcriptase inhibitors, and protease inhibitors. CRF02_AG was more predominant, and the frequency of resistant subtypes was high. However, these data will contribute to the therapeutic choice during the initiation of antiretroviral treatment in treatment-naive patients in Gabon.

HIV psychiatry may be the missing link to HIV prevention and care. Although HIV has been transformed from a fatal illness to a chronic and manageable illness, morbidity and mortality from HIV and AIDS continue to persist despite advances in prevention and care. In the 42 years since the HIV pandemic began in 1981, >84 million people were infected with HIV and 40 million people with HIV have died. In 2021, 1.5 million were newly infected and as of 2022, >38 million people were living with HIV.

HIV-1CRF08_BC is the most prevalent epidemic subtype among heterosexual (HET) and intravenous drug users (IDUs) in Kunming, Yunnan. Using the pol region of gene sequences derived from molecular epidemiological surveys, we developed a molecular transmission network for the purpose of analyzing its epidemiological characteristics, assessing its epidemiological trends, identifying its potential transmission relationships, and developing targeted interventions. HyPhy 2.2.4 was used to calculate pairwise genetic distances between sequences; GraphPad-Prism 8.0 was employed to determine the standard genetic distance; and Cytoscope 3.7.2 was applied to visualize the network. We used the network analysis tools to investigate network characteristics and the Molecular Complex Detection (MCODE) tool to observe the growth of the network. We utilized a logistic regression model to examine the factors influencing clustering and a zero-inflated Poisson model to investigate the factors influencing potential transmission links. At the standard genetic distance threshold of 0.008, 406 out of 858 study participants were clustered in 132 dissemination networks with a total network linkage of 868, and the number of links per sequence ranged from 1 to 19. The MCODE analysis identified three significant modular clusters in the networks, with network scores ranging from 4.9 to 7. In models of logistic regression, HET, middle-aged and elderly individuals, and residents of northern and southeastern Kunming were more likely to enter the transmission network. According to the zero-inflated Poisson model, age, transmission category, sampling year, marital status, and CD4⁺ T level had a significant effect on the size of links. The molecular clusters in Kunming's molecular transmission network are specific and aggregate to a certain extent. HIV-1 molecular network analysis provided information on local transmission characteristics, and these findings helped to determine the priority of transmission-reduction interventions.

The challenge of designing future HIV prevention efficacy trials in a rapidly evolving HIV prevention landscape was explored through a series of virtual stakeholder's engagement meetings convened online between October 2020 and April 2021. A broad array of stakeholders from the HIV prevention research community reviewed current trial designs and lessons learned, explored issues specific to unique product classes, and concluded with specialist-focused examinations of statistical design concepts and the importance of community engagement in research. The aim was to reflect on current approaches and evaluate new trial design approaches for evaluating efficacy of a candidate prevention strategy in the context of an active-controlled trial, which does not include a placebo arm. In this report, we provide a summary of the discussion points that included gaps in understanding and logical next steps in the prevention research pathway. The technical challenges involved in the statistical design approaches are described in a companion article.

We sought to describe the prevalence of and motivation for cannabis use and whether legalization of cannabis impacts the frequency and perceived risks and benefits of use in people living with HIV (PWH). The study was based on two HIV clinics located in Cleveland, Ohio, and Aurora, Colorado. Participants responded to a 45-question survey, and responses were summarized in aggregate and stratified by the frequency of cannabis use and site. Three hundred ninety-seven participants completed the survey. The frequency of use was not different between the sites. Daily cannabis users compared with yearly or never users identified the benefits of cannabis as relief from stress, anxiety, or depression, improved sleep, improved creativity, improved focus or concentration, and increased energy. The benefits of pain management, improved appetite, and helping to decrease or stop other medications were selected at similar rates, regardless of the frequency of use. Daily users were less likely to identify treatment of disease as a benefit and legal problems, addiction to cannabis, impaired memory, increased use of other drugs, personal or relationship problems, decrease in intelligence, new or worsening health problems, and getting high as risks of use compared with yearly or never users. Compared with participants in Ohio, Coloradoans were more likely to identify cannabis benefits as decreasing/stopping other medications and getting high, and less likely to identify legal problems and addiction as risks. Legalization of cannabis did not affect the frequency of cannabis use in PWH. Daily cannabis users are more likely to identify benefits and less likely to identify risks of use compared with yearly or never users. A better understanding of the potential benefits and risks of cannabis use can help guide safer use of cannabis in PWH and allow physicians to provide better counseling on risk reduction.