AIDS research and human retroviruses最新文献

Little is known about the relationships between circulating short-chain fatty acids (SCFAs) and genital microbiota, inflammation, and the risk for HIV infection in women. As circulating SCFAs are potentially modifiable, for example, through dietary fiber or probiotics, we investigated association of circulating SCFA levels with these outcomes. We carried out a nested matched case-control study within a randomized trial of an antiretroviral microbicide to prevent HIV infection to study the association between circulating SCFAs and HIV acquisition (primary outcome for case definition), vaginal microbiota, and genital inflammation. Levels of the SCFAs butyrate, acetate, and propionate were quantified in plasma using mass spectrometry. Vaginal microbiota was assessed using metaproteomics and characterized as Lactobacillus dominant (LD) or low Lactobacillus (LL). Genital inflammation was measured using multiplex immunoassays. Logistic regression models were used to study the association of SCFAs with each outcome. Study population (N = 99) characteristics were similar between cases (33 who acquired HIV) and controls (66 who did not acquire HIV). We did not observe any associations between any of the circulating SCFAs with HIV acquisition or with LL vaginal microbiota status. However, there was an inverse association between circulating SCFAs and several pro-inflammatory genital cytokines, including interleukin-6 (IL-6), IL-1α, and IL-8. In our study of women with high risk of HIV infection, higher levels of circulating SCFAs were associated with lower levels of various genital inflammatory markers, but not with HIV acquisition or a LL microbiota profile. Future larger studies, including genital SCFA assessment, are needed to confirm these findings.

Pregnancy affects adiposity, which may be influenced by HIV infection or antiretroviral therapy (ART). The objective of this study was to examine adiposity measures in the perinatal period, by HIV status and ART class. A total of 214 women (113 women with HIV [WWH], 71 initiated ART postconception), enrolled between 24 and 28 weeks of gestation and followed until 6-12 months postpartum, were assessed for longitudinal weight and cross-sectional postpartum anthropometry. A subset of 65 (52 WWH, 42 initiated ART postconception) had cross-sectional adiposity (body composition and fat distribution) measured at 6-12 months postpartum using dual-energy X-ray absorption scan. Multivariable linear and modified Poisson regression, adjusted for maternal age, pre-pregnancy body mass index, socioeconomic status, and postpartum months, examined associations of HIV status and postconception ART (dolutegravir-based [DTG] vs. efavirenz-based [EFV]) with anthropometry and adiposity outcomes. At enrollment, the median age was 30 years (interquartile range, 26-34) and 82% were multiparous. Between pre-pregnancy and postpartum, women gained an average of 2.33 kg (0.90 kg WWH), 30% lost weight (35% WWH), and 48% gained weight (38% WWH). WWH gained weight slower during pregnancy (0.27 vs 0.38 kg/week, p = .03) and were less likely to gain weight postpartum (RR = 0.72 95% CI 0.55, 0.93; p = .01) compared with women without HIV. Postpartum, mean body mass index was 32 kg/m² (standard deviation = 7.33) and 58% (53% WWH) of women had obesity. HIV was not associated with cross-sectional measures of postpartum anthropometry and adiposity. Among WWH, compared with EFV-based ART, DTG-based ART was not associated with weight gain during pregnancy or anthropometry and adiposity postpartum. Despite high rates of postpartum weight gain and obesity, no significant differences were observed in anthropometry and adiposity measures by HIV status and postconception ART. Nonetheless, these findings underscore the need for interventions to support healthy weight gain in pregnancy and postpartum weight loss to minimize pregnancy-associated obesity.

Accumulating evidence indicates that HIV acquisition may be associated with premature aging. However, the causal relationship and the direction of the effect between HIV acquisition and aging remain controversial. In the present study, we aimed to investigate the causal associations between HIV acquisition and biological aging. Summary data for biological aging proxy and HIV acquisition were collected from the most updated and available genome-wide association studies. Biological aging proxied by telomere length (TL) and four epigenetic clocks, including intrinsic epigenetic age acceleration, GrimAge acceleration, HannumAge acceleration, and PhenoAge acceleration. Four Mendelian randomization (MR) methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and weighted mode, were used to assess causal associations. Multiple sensitivity analyses, including heterogeneity analysis, leave-one-out sensitivity analysis, and horizontal pleiotropy analysis, were further performed to verify the robustness of our findings. The IVW MR results indicated that genetically predicted HIV acquisition was not significantly associated with biological aging (all p > .05). Similarly, the reverse-direction MR also did not identify potentially causal effects of biological aging on HIV acquisition (all p > .05). This study found no obvious evidence of the causal relationship between HIV acquisition and biological aging. More studies are needed to future unravel the potential causal relationship and the exact mechanism.

Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) is a convenient, well-tolerated, once-daily, and single-tablet regimen. There are few data on its use during pregnancy. The primary objective was to evaluate the efficacy of BIC/FTC/TAF at delivery, defined as a plasma viral load <50 cp/mL. We conducted a retroprospective, single-center study including pregnant women living with HIV-1 who were on BIC/FTC/TAF. From January 2020 to January 2023, 12 women living with HIV-1 received BIC/FTC/TAF during pregnancy and at delivery. Two were receiving BIC/FTC/TAF at conception and remained on the same combination antiretroviral therapy (cART) throughout the pregnancy, and 10 received BIC/FTC/TAF at least during the third trimester and at delivery. Ten had a plasma viral load <50 cp/mL at delivery. The two who were not suppressed at delivery reported nonadherence to BIC/FTC/TAF, which was not related to treatment side effects. Reported tolerance was good. BIC/FTC/TAF might be a good option during pregnancy and particularly to simplify previous cART but it is necessary to counsel patients to ensure good adherence to this one.

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) pathology has been associated with Tax protein secreted from HTLV-1 infected CD4⁺-T-lymphocytes, which interacts with soluble SEMA-4D (Semaphorin 4D) inducing growth cone collapse in neurons. We investigated HTLV-1-induced phenotypic and signaling changes during PC12 neuronal differentiation that may mediate growth cone collapse effects. We measured kinases and phosphatases associated with microtubule-associated proteins and molecular motor functions. Phosphorylation status of proteins that participate in the cytoskeleton and axonal transport such as Tau, microtubule-associated protein 1B (MAP1B), motor proteins (kinesin-1 and dynein) and collapsin response mediator protein (CRMP-2), all involved in neurite extension and branching, were measured. The phosphorylation/dephosphorylation of these proteins is catalyzed by Cyclin-dependent kinase-5 (CDK5), Glycogen synthase kinase-3β (GSK3β), and Protein phosphatase-2 (PP2A). Our results show that viral secreted proteins produced a reduction of neurite extension and branching in PC12 cells during neuronal differentiation. We observed that GSK3β activity increased, while CDK5 and PP2A activities decreased. In addition, we found reduced levels of Tau phosphorylated at Thr¹⁸¹ and increased levels of CRMP-2 phosphorylated at Ser⁵²². No changes in motor proteins or MAP1B phosphorylation were found. Neurotoxic effects of HTLV-1 secreted proteins on neuronal differentiation of PC12 cells include lower CDK5 activity, which could explain the reduced levels of Tau-(pThr¹⁸¹); this could induce conformational changes in Tau protein, altering microtubule dynamics. Increased CRMP-2-(pSer⁵²²) phosphorylation precedes further phosphorylation at Thr⁵⁰⁹/⁵¹⁴ residues by GSK3β. All these phosphorylations are associated with growth cone collapse. The increased CRMP-2-(pSer⁵²²) levels found here suggest that CDK5 activity, even when decreased, is sufficient for this priming phosphorylation. Reduction in PP2A activity could importantly contribute to maintaining the increased phosphorylation in CRMP-2. These results suggest the involvement of extracellular Tax/sSEMA-4D complex in the activation of Plexin1B receptor, activating downstream cascade involving PI3K/AKT/GSK3β/CRMP-2, inducing growth cone collapse.

HIV cure-related clinical research studies often include analytical treatment interruptions (ATIs), in which participants pause antiretroviral treatment (ART). During ATIs, researchers closely monitor laboratory values and adverse events. We assessed and compared the perspectives of two distinct groups of participants: HIV noncontrollers and controllers in a San Francisco-based ATI study focused on identifying biomarkers predicting HIV viral rebound. Data were collected from 2021 to 2024 over five study time points to assess motivations, understanding of the study, decisional regret, and partner protections. All participants (n = 16) endorsed the goal of helping advance HIV research as a motivator, about half were also driven by interest in their body's response to the ATI, and some indicated monetary compensation as a key motivator. Most participants (6 of 10 noncontrollers and 4 of 6 controllers) did not view personal health benefit as a primary study goal. All understood the option for an extended ATI if they had not met ART restart criteria after 28 days. At the study's onset, all sexually active participants (n = 14) were informed about the risk of transmission to sex partners and the need for partner protections during ATIs. Among noncontrollers, 2 of 5 reported using condoms, being abstinent or partner use of pre-exposure prophylaxis (PrEP) during sexual activity. Among controllers, 3 of 5 reported sexual activity: one with a partner on PrEP, one with a partner on ART, and one using other protection methods. Decisional regret about study participation, measured on a scale of 0-100, was low among both noncontrollers (range 1.67-13.57), and controllers (range 8.33-10) during the ATI, and remained low following it (noncontroller M = 5.07, SD = 4.52; controller M = 10.00, SD = 11.31). Participants generally understood the study, highlighted the need for partner protection support during ATI, and reported low decisional regret.

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.