AIDS research and human retroviruses最新文献

Heterosexual transmission (HETE) represents the predominant method of transmission for the human immunodeficiency virus type 1 (HIV-1) in Shijiazhuang, Hebei Province, China. The number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) continues to increase in this region. In the present study, two novel URFs (TFH010919 and TFH010944) were identified, both derived from HETEs in the Shijiazhuang area. The phylogenetic and recombination breakpoint analyses conducted on the near-full-length genomes of the two novel URFs revealed that the CRF01_AE strains serve as the predominant backbones for both TFH010919 and TFH010944. TFH010919 is a second-generation recombinant form composed of CRF01_AE and CRF07_BC, whereas TFH010944 is formed by the combination of CRF01_AE and CRF68_01B. This finding indicates that HIV-1 prevalence among HETEs remains a significant concern, driven by complex sexual networks that facilitate the spread of diverse recombinant strains, providing more opportunities for the recombination of viruses. The emergence of these new URFs revealed the ongoing evolution of HIV-1 and underscores the critical need for continuous monitoring of viral diversity in Hebei Province and surrounding regions to control HIV-1 transmission within the vulnerable population and beyond.

Molecular transmission networks are being used with increasing frequency to study HIV-1 transmission patterns and to develop precise intervention strategies for high-risk populations. Here, we analyzed the molecular transmission networks of newly diagnosed patients with HIV-1 in Hefei City, Anhui Province, from 2017 to 2022. Of the 1,413 newly diagnosed HIV-1 Pol sequences, the major genotypes in Hefei were CRF07_BC (600, 42.5%) and CRF01_AE (530, 37.5%). Molecular transmission network analysis identified 146 clusters and 9 large propagation clusters, including four CRF01_AE clusters, four CRF07_BC clusters, and one CRF55_01B cluster. This study highlights the pattern of local HIV-1 transmission in Hefei City, with notable rapid transmission of CRF55_01B. It suggests that the implementation of focused strategies for the identified key transmission clusters is essential for effective control of the HIV-1 epidemic.

Since combined antiretroviral therapy for human immunodeficiency virus-associated neurocognitive dysfunction (HAND) only slows the disease's progression, early identification and timely intervention are crucial for effective therapy. In this article, we review the latest evidence in body fluid biomarkers of HAND, providing an overview of research conducted on cerebrospinal fluid and blood samples to draw conclusions on promising biomarkers. Although the significance of biomarkers such as amyloid metabolites, tau proteins, neurofilament light chain, myelin oligodendrocyte glycoprotein, and brain-derived neurotrophic factor in the early detection of HAND may not be immediately clear, they could potentially play a crucial role in evaluating prognosis and tracking the effectiveness of treatment.

Current trials toward an HIV cure involve combination strategies aimed at achieving durable antiretroviral treatment (ART)-free viral control or HIV elimination, many relying on analytical treatment interruptions (ATIs) to evaluate efficacy. Given the physical, psychosocial, and interpersonal risks associated with ATIs, it is critical to monitor participants' experiences so that support can be provided when needed. While qualitative approaches have been used in similar settings, we designed and implemented a series of short, closed-ended participant surveys in the University of California, San Francisco-amfAR trial, a single-arm multi-intervention HIV cure-related trial with an extended ATI. Surveys were administered at relevant trial timepoints to capture participants' (n = 10) perspectives and experiences. These included their understanding of the trial, motivations, expectations, perceived risks, benefits, and burdens of trial participation, and their perspectives on restarting ART and partner protections. We describe these data using descriptive statistics and summarize lessons learned from implementing quantitative surveys in this complex trial. Our data indicate that all respondents understood the scientific goals and requirements of participating in the trial. Most were motivated to help advance research but many expressed anxiety about participating. During the trial, respondents had limited side effects, discomfort, and trial burnout. Those who completed surveys at ART restart reported mixed (positive and negative) feelings and challenges (e.g., missed doses) when restarting ART. Participants offered various methods for partner protection during ATIs and at ART restart. Many respondents expressed future willingness to participate in a similar HIV cure trial. While the number of respondents was small, these findings are consistent with concerns identified in guidance regarding these types of trials as well as qualitative findings from earlier studies. Moreover, we demonstrated that it is feasible to implement quantitative evaluations of participants' experiences. Such approaches should be implemented in future HIV cure trials to optimize human-centered research implementation.

Previously, we reported a T69S insertion in the circulating recombinant form 06_cpx in a patient infected with HIV-1 during the perinatal period. Through this study, we found that the T69S insertion in our previous report was actually an S68S insertion. The patient was treated with zidovudine and didanosine, followed by combination antiretroviral therapy. The introduction of Korean Red Ginseng (KRG) completely suppressed plasma viral RNA to <20 copies/mL and reverted the S68S insertion to wild-type; there was no evidence of an S68S insertion for 3 years. Here, we report the impact of integrase strand transfer inhibitor (INSTI) treatment on drug resistance mutations (DRMs) over a further 10 years. The S68S insertion disappeared after 3 months of INSTI therapy, and the number of DRMs decreased. There were no major DRMs to INSTI in either the patient or her parents. These data highlight the utility of combination therapy with INSTI and KRG.

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) provides an effective treatment option for people with HIV (PWH). Studies suggest that PWH on LAI CAB/RPV may experience isolated episodes of transient viremia (HIV RNA > 20 copies/mL) defined as virologic blips (VB). The risk factors for VB in PWH receiving LAI CAB/RPV are limited. We aimed to describe a cohort of PWH on LAI CAB/RPV and evaluate risk factors and time to VB following LAI CAB/RPV initiation. We obtained DC Cohort data from PWH who initiated LAI CAB/RPV prior to July 2023 and used Kaplan-Meier curves and Cox proportional hazards models to evaluate the association between participant demographics, HIV clinical factors, and time to VB. Among 98 PWH who initiated LAI CAB/RPV, 9 (9.2%) experienced at least one VB (median HIV RNA = 50 copies/mL; ranges 30-12,000 copies/mL) during a median follow-up period of five months (IQR: 2-10). The median CD4 count among PWH was 754 cells/µL (IQR: 598, 980) at the time of LAI CAB/RPV initiation. Having a high CD4 (≥ 500 cells/μL) at LAI CAB/RPV initiation was significantly associated with a lower hazard for VB when compared to baseline CD4 < 200 cells/µL [hazard ratios (HR): 0.15 [95% confidence intervals (CI): 0.03, 0.77]; aHR: 0.07 (95% CI: 0.01, 0.50); log-rank p = .026]. No other characteristics were significantly associated with time to VB, and no participants experienced virologic failure. Considerations for baseline CD4 may be important when initiating a patient on LAI CAB/RPV, and future studies will help evaluate the VB occurrence and associated factors among PWH.

Daily oral medication is currently the most common antiretroviral therapy (ART) for people living with human immunodeficiency virus (PLWH). As the first complete long-acting (LA) ART regimen, cabotegravir (CAB) and rilpivirine (RPV), offer a novel treatment approach with less frequent administration, via bimonthly infusion. Due to the upcoming availability of this regimen in China, the study aimed to analyze the willingness and reasons of PLWH to switch to CAB+RPV therapy. A questionnaire survey among PLWH receiving oral ART was carried out between March 25 and April 8, 2023, in the Second Hospital of Nanjing, China. Participants were asked about their willingness to switch to the CAB+RPV LA regimen and provided reasons for their decision. We analyzed the reasons for switching, and the factors affecting their willingness were analyzed by multinomial logistic regression. Among 693 participants, 56.7% expressed willingness to switch to the CAB+RPV regimen, 32.6% were uncertain, and 10.7% were unwilling. The primary reason for switching to CAB+RPV therapy was not being concerned about daily adherence to ART (22.6%). Uncertainty about switching was mainly associated with participants' concerns in terms of price (31.6%) and safety (31.1%) of the novel drugs. Unwillingness was mainly due to participants' satisfaction with their current treatment regimen (20.3%). In multivariate analysis, higher education (odds ratio [OR]: 2.990; 95% confidence interval [CI]: 1.171-7.636) was positively associated with willingness to switch, whereas the age of ≥60 (OR: 0.142; 95% CI: 0.036-0.554) was negatively associated. Our survey demonstrated that the majority of PLWH were willing to switch to CAB+RPV therapy, mainly due to its improved convenience and reduced risk of disease exposure. However, their concerns regarding price, efficacy, and safety could be the key challenges for the clinical implementation of the CAB+RPV LA regimen in the future.

The human immunodeficiency virus (HIV), a retrovirus targeting the immune system and the primary agent causing acquired immunodeficiency syndrome (AIDS), can have fatal consequences. Although antiretroviral treatment has significantly reduced mortality and comorbidity in people living with HIV (PLHIV), its impact on metabolic syndrome (MetS) remains notable. Several genome-wide association studies have identified a link between the glucokinase gene (GCK) and MetS, particularly in type 2 diabetes. However, no studies have investigated the association between this gene and HIV status. Our study aims to evaluate the association of the rs1799884 polymorphism in the GCK gene with HIV status in a group of Moroccan patients. This case-control study includes 207 PLHIV and 181 HIV-uninfected controls. Genotyping of the rs1799884 polymorphism in the GCK gene was performed using a predesigned TaqMan single-nucleotide polymorphism genotyping assay. The genotypic distribution between PLHIV and HIV-uninfected controls revealed a significant difference. Patients with the CT genotype had a 4.47-fold increased risk of infection [odds ratio (OR) = 4.47; 95% confidence interval (CI) = 2.75-7.29; p = .001]. However, the TT genotype conferred protection against HIV in a recessive model (OR = 0.50; 95% CI = 0.28-0.91; p = .021). Interestingly, the risk associated with the CT genotype was even higher in AIDS-related cases (OR = 9.37; 95% CI = 4.32-20.36; p = .0001). Additionally, under the dominant model, individuals with CT and TT genotypes had a 7.67-fold increased risk of infection (OR = 7.67; 95% CI = 3.60-16.36; p < .0001). However, the TT genotype under the recessive model was not significantly associated with disease progression. No significant association was observed between these genotypes and CD4 count; however, there was a significant variation in viral load after treatment. Our findings suggest that the rs1799884-C/T variant of the GCK gene may influence susceptibility to HIV status, progression to AIDS, and response to treatment.

Data on persons with perinatally acquired HIV infection in the Caribbean are limited; thus, a chart review was conducted among these clients at an adult HIV treatment clinic in Trinidad over the period January 01, 2011-June 30, 2023. Sociodemographic, clinical, and laboratory data were extracted and analyzed using RStudio version 2021.09.0. Fifty-four study participants were followed up, age range 18-29 years, and there were 27 (50%) males. Eighteen participants (33.3%) were institutionalized until the age of 18 years, while 36 (66.7%) lived with caregivers/relatives and attended outpatient pediatric clinic. The transition from the sheltered environment of pediatric care to the adult HIV clinic was turbulent for some participants as they experienced HIV-related stigma, which may result in poor HIV outcomes. At the initial clinic visit, 28 (51.9%) study participants were virally suppressed (HIV viral load <1,000 copies/mL), which included 12 (66.7%) of 18 who were institutionalized as compared to 16 (44.4%) of 38 who lived with caregivers/relatives (p = 0.387). Data from their last clinic visit showed 31 (57.4%) participants were virally suppressed; 13 (24.1%) were lost to follow-up from care, and there were 6 (11.1%) deaths; 29 (53.7%) were on antiretroviral therapy single-tablet regimens (STRs) and 25 (46.3%) on complex multiple-tablet regimens (MTRs). Institutionalized clients and those on STRs were more likely to be virally suppressed than those living with relatives (p = 0.043) and those on MTR (p < 0.001), respectively. Reported deaths were higher among clients who lived with caregivers/relatives and those on MTR. Participants of younger age were less likely to achieve viral suppression (p = 0.02). Comprehensive programs that include STRs, the engagement of caregivers/relatives and health workers, life skills, and enhanced psychosocial interventions for youths living with perinatally acquired HIV are important to support the transition to adult care and reduce the complex challenges of living with a stigmatizing disease.

The Aim of this study is to assess the cardiovascular safety of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF). We analyzed data from 37 virologically suppressed people living with HIV starting DOR/3TC/TDF, collecting viro-immunological and metabolic parameters as well as the 10-year risk of cardiovascular disease (10Y-CD) using both the Framingham risk score and D:A:D score.After 48 weeks, we observed a significant reduction in 10Y-CD both via the Framingham score (-0.7, p = .021) and the D:A:D score (-0.41, p = .012). After 96 weeks, we registered a significant reduction in 10Y-CD calculated via the D:A:D score (-0.98, p = .009). Regarding serum lipid markers, after 48 weeks we observed a significant reduction in total cholesterol (-17 mg/dL, p < .001), triglycerides (-21 mg/dL, p = .015), and LDL cholesterol (-8 mg/dL, p = .022). After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, p < .001). DOR/3TC/TDF has shown a favorable metabolic profile, with a significant reduction in 10Y-CD, independently from the use of lipid-lowering drugs.