AIDS research and human retroviruses最新文献

Heterosexuals have become the most prevalent group of HIV-1 in Kunming, Yunnan Province. Utilizing the principle of genetic similarity between their gene sequences, we built a molecular transmission network by gathering data from earlier molecular epidemiological studies. This allowed us to analyze the epidemiological features of this group and offer fresh concepts and approaches for the prevention and management of HIV-1 epidemics. Cytoscope was used to visualize and characterize the network following the processing of the sample gene sequences by BioEdit and HyPhy. The number of possible links and the size of the clusters were investigated as influencing factors using a zero-inflated Poisson model and a logistic regression model, respectively. A scikit-learn-based prediction model was developed to account for the dynamic changes in the HIV-1 molecular network. Six noteworthy modular clusters with network scores ranging from 4 to 9 were found from 150 clusters using Molecular Complex Detection analysis at a standard genetic distance threshold of 0.01. The size of the number of possible links and the network's clustering rate were significantly impacted by sampling time, marital status, and CD4⁺ T lymphocytes (all p < 0.05). The gradient boosting machine (GBM) model had the highest area under the curve value, 0.884 ± 0.051, according to scikit-learn. Though not all cluster subtypes grew equally, the network clusters were relatively specific and aggregated. The largest local transmission-risk group for HIV-1CRF08_BC is now the heterosexual transmission population. The most suitable model for constructing the HIV-1 molecular network dynamics prediction model was found to be the GBM model.

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.

Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human health and how climate change phenomena - including extreme weather events, food insecurity, pollution, and emerging diseases - may exacerbate immune dysfunction and comorbidities faced by PLWH and hinder access to HIV treatment and prevention services. Multidisciplinary, collaborative efforts are urgently needed to quantify these impacts, develop mitigation strategies, and strengthen policies and funding to bolster immune resilience for PLWH in the face of accelerating climate change.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4⁺ cell count was 1,235 cells/mm³ [n = 51] at baseline, 1,690 cells/mm³ (n = 41) at Week 48, and 1,280 cells/mm³ (n = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.

Mother-to-child transmission (MTCT) of HIV-1 and associated mortality continue to occur at unacceptably high rates, despite the extensive rollout and implementation of Prevention of Mother-to-Child Transmission (PMTCT) Programs, including the modified versions of Option B and B+ in 2010 and 2012, respectively. Maternal HIV viral load (VL) and socio-behavioral factors sustaining MTCT in Rwanda remain largely unexplored. The study examined the effects of socio-behavioral factors on maternal VL and their contribution to in utero transmission of HIV-1 in the context of Rwanda's HIV epidemic. A prospective cohort study was conducted in 862 mother-baby pairs enrolled in 10 PMTCT clinics in Rwanda. VL was determined on plasma and Dried Blood Spots samples, whereas HIV DNA PCR was performed to determine in utero MTCT of HIV of the babies immediately at birth and then at 3 weeks, 4 weeks, 6 months, and 18 months, together with HIV antibody testing to determine other forms of MTCT of HIV. Quantitative data on socio-behavioral factors were collected through a structured questionnaire. Linear regression and univariate analysis of variances using SPSS 25.0 were used to test the hypotheses. We found 22/862 (2.55%) cases of in utero transmission and a total of 32/862 (3.7%) cases of MTCT of HIV-1 over 18 study months. Maternal VL at delivery was significantly associated with the risk of in utero transmission of HIV-1. Socio-behavioral factors associated with elevated maternal VL at delivery included alcohol, smoking, multiple sexual partners, mothers' income, being a casual laborer, and distance to health care services. We report an MTCT rate of 3.7% in our study population over the 18 months, higher than the national average of 1.5%, the majority of which occurred in utero. MTCT cases were attributable to failure to suppress maternal VL.

To improve current and future use of existing (oral, injectable) and potential future (implants, douches) pre-exposure prophylaxis (PrEP) products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the United States, South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches. Next, they completed a choice exercise in which they were shown 10 screens, each presenting 3 of the aforementioned products at a time with 11 attributes for physicians and 10 attributes for GBM. For the attributes that were not constant, one level was shown per screen for each product. Participants selected the product they preferred most and rated their likelihood to select (GBM) or recommend (physicians) that product. Data were modeled using hierarchical Bayes estimation; resulting model coefficients were used to develop attribute importance measures and product preferences. For GBM across all countries, if all aforementioned PrEP products were on the market at the same time, over 90% of GBM would use some form of PrEP; 100% of physicians would recommend at least one of the PrEP products. There were variations in product preference by country. GBM in the United States and Thailand preferred the injection (21.7%, 22.9%, respectively), while the dissolvable implant was preferred in South Africa and Spain (19.9%, 19.8%, respectively). In the United States, South Africa, and Spain (where physician data were available), physicians were most likely to recommend the dissolvable implant (37.2%, 40.6%, 38.3%, respectively).

Functional magnetic resonance imaging (fMRI) studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz (EFV), an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of EFV on reward processing using a monetary incentive delay (MID) task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil fumarate (FTC/TDF)/EFV were randomly assigned in a 2:1 ratio to switch to FTC/TDF/rilpivirine (RPV) (n = 30) or continue taking FTC/TDF/EFV (n = 13). At baseline and 12 weeks after therapy switch, both groups performed an MID task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood-oxygen-level-dependent fMRI. Both groups were matched for age, education level, and time since HIV diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus nonrewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.

With the prevalence of human immunodeficiency virus type 1 (HIV-1) CRF01_AE and CRF07_BC subtypes in China, the co-circulation of multiple subtypes in the HIV-1-positive population may result in dual infection or superinfection in the population, leading to the emergence of unique recombinant forms (URFs) of the HIV-1 virus. In this study, two second-generation unique recombinant strains, BI0114 and BI0116, were identified, and their near full-length genome sequences were obtained. Recombination analysis showed that both sequences were isoforms of URF_0107, and they were second-generation unique recombinant strains formed by the recombination of CRF01_AE and CRF07_BC, with the isoforms being CRF01_AE and CRF0107_BC, respectively. The continued emergence of novel CRF01_AE/CRF07_BC recombinant strains suggests that the epidemiological, preventive, and control situation of HIV-1 is complex and that the relevant health authorities urgently need to establish responses to the challenges posed by changes in the pattern of strain recombination.