AIDS research and human retroviruses最新文献

Various modalities are being explored in HIV cure-related research, but little is documented on their acceptability in Africa, where HIV is most prevalent. To address this, we conducted a cross-sectional study in Soweto, South Africa, assessing stated acceptability of five potential HIV cure-related research modalities and identifying associated factors. Between May and August 2024, we sampled 100 adults living with HIV who provided informed consent. Participants completed questionnaires of socio-demographics and the Theoretical Framework of Acceptability scale measuring general acceptability and seven constructs (affective attitude, burden, ethicality, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs). We summarized data using descriptive statistics. We assessed factors associated with acceptability using univariate and multivariate logistic regression. We found that of 100 participants (44% female, median age 39 years), 66% were willing to accept an intervention that would allow lifelong remission (antiretroviral treatment-free control), 88% were willing if the intervention guaranteed remission for everyone treated, and 87% were willing if the intervention had minimal side effects. Total mean acceptability scores of hypothetical HIV cure-related research modalities were oral or injectable chemotherapeutics (3.8/5), intravenous or injectable antibodies (3.7/5), radiotherapy (3.3/5), transplantation (3.1/5), gene therapy (2.9/5), and across all modalities (3.4/5). Participants rated antibodies and chemotherapeutics with tied top scores for affective attitude (3.8/5) and self-efficacy (4.0/5); chemotherapeutics with top scores for perceived effectiveness (4.0/5), intervention coherence (4.1/5) and having least burden (3.2/5) and opportunity costs (3.3/5); and antibodies with the top score for ethicality (4.2/5). Acceptability was associated with non-binary gender and willingness to take an intervention achieving 2 years remission. In conclusion, people living with HIV have moderately high acceptability for oral or injectable chemotherapeutics and intravenous or injectable antibodies but would need more information about gene therapy, transplantation, and radiotherapy. Antibodies aligned highest with personal values, suggesting support for antibody research and applications.

The genetic diversity of HIV-1, driven by mutation and recombination, poses significant challenges to prevention and control efforts, particularly in regions like China where multiple subtypes and circulating recombinant forms co-circulate. Men who have sex with men (MSM) represent a key population for the emergence of novel recombinants. This study characterizes two novel unique recombinant forms (URFs) identified within the MSM population in Hebei, China. Viral RNA extraction, amplification, and near full-length genome (NFLG) sequencing were performed. Phylogenetic analysis based on NFLG alignments was conducted in MEGA 6 under the Kimura 2-parameter model with 1,000 bootstrap replicates. Recombination was assessed using the Recombinant Identification Program and SimPlot v3.5.1. Breakpoint-defined regions were phylogenetically analyzed, and recombination maps were generated. Phylogenetic and recombinant analysis based on NFLG sequences (designated BDL061 and BDL071) revealed that they originated from subtypes B and C. BDL061 exhibited a predominantly subtype B backbone with interspersed subtype C segments, while BDL071 displayed a predominantly subtype C backbone with subtype B segments. Phylogenetic analysis of recombinant segments strongly supported (bootstrap >90%) subtype B and C parental origins for the respective fragments. We report the identification and characterization of two phylogenetically distinct, novel HIV-1B/C URFs (BDL061 and BDL071) among MSM in Hebei, China. Their unique mosaic structures, differing predominant backbones, and confirmation as novel recombinants underscore the ongoing evolution and increasing complexity of the HIV-1 epidemic within this high-risk population in China. These findings highlight the critical need for NFLG-based surveillance to accurately track viral diversity and inform public health strategies.

The frequent recombination between subtypes has driven significant HIV-1 genetic diversity in recent years, especially in some areas with co-circulation of multiple subtypes. In this study, we obtained nearly full-length genome sequences of two novel HIV-1 B/CRF01_AE/CRF07_BC recombinants from BD076A and BDL161, with lengths of 8718 bp (HXB2:772-9490) and 8851 bp (HBB2:759-9610), respectively. Both recombination breakpoint and Bootscanning analysis revealed that the recombinant structure of BD076A was based on the CRF07_BC backbone, with the insertion of one subtype B and one CRF01_AE gene fragment, containing four subregions. Similarly, BDL161 was based on the CRF07_BC backbone, with the insertion of one subtype B fragment and two CRF01_AE gene fragments, containing seven subregions. These findings highlight the importance of sustaining molecular epidemiological surveillance to monitor HIV-1 diversity and take effective prevention and control strategies in the region.

Estimating the prevalence and characterizing the HIV-1 transmitted drug resistance (TDR) are crucial for the prevention and control of HIV/AIDS. However, there are limited data currently on TDR among men who have sex with men (MSM) in Zhenjiang, Jiangsu, a high-risk population for drug resistance. We conducted a retrospective analysis among the newly diagnosed and antiretroviral therapy (ART)-naive HIV-1-infected MSM in Zhenjiang, 2012-2018. We analyzed the HIV-1 subtypes, TDR prevalence, TDR-associated mutations, and predicted drug sensitivity. Among these 192 participants, CRF01_AE (50.0%) and CRF07_BC (34.9%) were the predominant HIV-1 strains, with an increasing diversity of circulating subtypes (p < .05). A total of nine patients infected with CRF01_AE exhibited one or more TDR mutations, including 3.6% for Protease Inhibitor (PI)-related mutations, 1.0% for NRTI-related mutations and 1.0% for NNRTI-related mutations. The most common mutation was M46L/I for PIs. Notably, TDR prevalence showed an upward trend from 2012 to 2018, with an average of 4.7%. The gradually diversified subtypes, the increased TDR prevalence, and the potential risk of transmitting drug-resistant strains to the general population highlight the necessity of TDR monitoring in MSM. This will be beneficial for the prevention and control of HIV/AIDS in Zhenjiang.

Genotypic drug-resistance testing for HIV-1 with low viral loads (VLs) (<1,000 copies/mL) is clinically important but technically challenging. Due to the overlapping physical size characteristics of HIV-1 viral particles (100-120 nm) and exosomes (40-150 nm), simultaneous enrichment of both using size separation technology may offer a new strategy to improve the success rate of genotypic resistance testing in low VL samples. To evaluate the application of exosome enrichment technology in genotypic drug resistance testing for HIV-1 in low VL samples. We conducted a study with the following design. Whole blood samples were collected from HIV/AIDS patients at the Guiyang Public Health Treatment Center, who had been receiving antiretroviral therapy for over 6 months, with HIV-1 RNA levels ranging from 20 to 1,000 copies/mL, between June 2023 and November 2024. Plasma was separated, and HIV-1 RNA genotypic resistance testing was performed both directly on the plasma and after exosome enrichment. The amplification success rates of HIV-1 genotypic resistance testing before and after exosome enrichment were compared, and resistance mutation sites were analyzed. Among the 26 participants, 22 were male (84.62%) and 4 were female (15.38%), with a median age of 36.5 years. Exosome enrichment technology achieved amplification success rates for the HIV-1 genotypic resistance testing in the RT & PR regions and the INSTI region of 65.38% (17/26) and 42.31% (11/26), respectively, significantly higher than the pre-enrichment success rates of 19.23% (5/26) and 15.38% (4/26). These differences were statistically significant (χ² = 11.34, p = 0.001; χ² = 4.62, p = 0.032). Genotypic sequencing revealed K103N and L74M resistance mutations in two samples. These findings indicate that exosome enrichment technology enhances the amplification success rate of HIV-1 genotypic resistance testing in low VL samples and identifies clinically relevant resistance mutation sites. This approach may provide an innovative solution for resistance testing in low VL samples.

This study aims to assess the causal effect of syphilis on HIV infection by Mendelian randomization (MR) analysis. The data of syphilis and HIV infection were obtained from genome-wide association studies. Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database. Analysis involved the identification of key molecules and relevant signaling pathways. MR analysis showed a significant causal relationship between syphilis and HIV infection [weighted median, odds ratio (OR): 1.098, 95% confidence interval (CI): 1.033-1.217, p = .003; inverse variance weighted, OR: 1.095, 95% CI: 1.048-1.145, p < .001]. We discovered that rs138697742, a genetic variant related to the RPAIN gene, is associated with HIV infection and influences the expression of RPAIN, possibly contributing to the progression of the disease. Moreover, single-cell data analysis revealed the cellular communication patterns within PLWH, with monocytes appearing to play a crucial role. In summary, our study reveals a direct causal relationship between syphilis and HIV infection. Additionally, the upregulation of RPAIN gene expression resulting from genetic mutations may serve as a key factor in promoting the progression of HIV infection. Targeting the RPAIN/GALECTIN merges as a promising novel therapeutic target for managing HIV infection.

A short message service (SMS) intervention was implemented in July 2016 at eight health facilities (HFs) within Zambézia Province, Mozambique. We assessed effectiveness by comparing antiretroviral therapy (ART) pick-up rates among persons with HIV (PWH) eligible for SMS reminders. All adult (≥15 years of age) PWH enrolled in ART services reporting cell phone access were offered SMS. PWH were sent messages 15, 7, and 2 days before scheduled ART pick-up appointments. Using routine data (July 2016-May 2018), mixed-effect logistic regression was used to determine adjusted odds ratios (aORs) of ART pick-up within 2, 6, and 59 days of scheduled appointments, adjusting for age, sex, adherence support group status, partner status, pregnancy, education, occupation, years on ART, HF, pick-up day, and year-week. Data were available for 18,941 scheduled ART pick-up clinic visits for 3,222 PWH (52% female) reporting cell phone access. Overall, 47% of men and 46% of women consented to receive SMS. PWH sent reminders had higher pick-up rates within 2 days of scheduled appointments compared with those not sent reminders (54% vs. 51%). Men sent reminders were more likely to pick-up within 2 days of scheduled appointments than men not sent reminders [aOR = 1.22 (1.09-1.37)]. No association was seen within 6 or 59 days of scheduled appointments [aOR = 1.09 (0.95-1.25), 0.90 (0.74-1.10)]. Women sent reminders had similar pick-up rates compared with women not sent reminders [aOR = 0.94 (0.85-1.05), 0.90 (0.79-1.03), 0.89 (0.72-1.10)]. In Zambézia Province, SMS reminders were associated with timely short-term ART pick-up rates among men, although this association attenuated with increased time from scheduled appointment. Study limitations included its observational (nonrandomized) nature and restricting analyses to individuals reporting phone access. SMS reminders may be an important approach for addressing the well-documented need for medication adherence support for males. Additional context-specific strategies are needed to ensure timely ART pick-up and improve retention.

Despite advances in diagnosis and treatment, human immunodeficiency virus (HIV) infection still continues to be a globally important public health problem. While early diagnosis facilitates the control of the disease, late diagnosis can affect treatment success and prognosis adversely. This retrospective study evaluated the clinical and demographic characteristics of 127 treatment-naive people living with HIV who were older than 18 years of age and who were followed between 2017 and 2023 in a center in Thrace, a transitional region between Europe and Turkey, and the effects of early and late diagnosis on the course of disease were examined. It was found that 89% of the patients were male, and median age was 30 years. Of the patients, 52% had been diagnosed late, and this group was found to be older. The rate of advanced HIV disease was 28.3%. The rates of additional chronic disease (42.4%), opportunistic infection, and diagnosis with clinical symptoms were higher in the late diagnosis group. CD4 T lymphocyte levels were lower, and viral load was found to be higher in this group. At the sixth month of treatment, the rate of virologic response was found to be better in the early diagnosis group. In the late diagnosis group, immunological response was also limited, and hospitalization (40.9%), need for intensive care (12.1%), and mortality (4.5%) rates were higher in this group. These findings demonstrate the prevalence of late diagnosis in the Thrace region and its significant effects on the clinical course of HIV infection. They also emphasize the importance of targeted screening and early diagnosis strategies in border regions.

In persons living with HIV (PWH), non-AIDS-related tumors, including colorectal cancer (CRC), have become major health concerns worldwide since the introduction of highly active antiretroviral therapy. To date, no study has addressed the underlying molecular mechanisms in PWH with CRC. To explore the impact of PWH with CRC, we sequenced total RNA and DNA from individuals with HIV-negative and PWH formalin-fixed paraffin-embedded (FFPE) CRC for transcriptome and genome analyses. We performed RNA and DNA extraction from FFPE samples, library preparation, total RNA sequencing, and whole-genome sequencing. A total of 1,705 genes were found to be differentially expressed genes (DEGs), including 1,121 upregulated DEGs and 584 downregulated DEGs, in PWH compared with HIV-negative CRC. Functional pathway analysis revealed that the DEGs were enriched mainly in infectious and immune diseases and various metabolic processes. The immune infiltration results revealed that the numbers of activated dendritic cells (aDCs), natural killer T cells (NKT cells), and T follicular helper cells (Tfh cells) were greater and that the number of memory B cells was lower in patients with CRC than in PWH. Twelve hub genes involved in interferon-stimulated genes (ISGs)-IFI44, MX1, OAS1, OAS3, BST2, IFIT1, FGF2, EGF, CCL3, CCL4, SHH, and PPARG-are positively related to aDC, NKT, Tfh, and memory B cells. We found highly analogous insertions, deletions, and functional annotations of the detected single nucleotide polymorphisms and indel mutations in PWH and patients with HIV-negative CRC. This study provides new insights into crucial ISGs, immune infiltration, immune variants, and pathways involved in CRC with HIV infection.

When local epidemiology of endemic fungal infections is poorly understood, it is difficult to determine the clinical impact of screening for these pathogens in people living with HIV. We found no Histoplasma urine antigen or serum antibody in over 450 symptomatic patients with a new diagnosis of HIV in Port-au-Prince, Haiti. These findings indicate that systematic testing is likely to be low yield in Port-au-Prince, although it is well described in other countries in the region, and may have higher prevalence in rural areas. These findings are relevant to other settings where the prevalence of histoplasmosis is poorly defined, as similar studies could also inform local evidence-based guidelines.