AIDS research and human retroviruses最新文献

This study focuses on HIV-1-infected women of childbearing age in Liangshan Prefecture and analyses their HIV-1 RNA and HIV-1 DNA genotypic drug resistance to provide a theoretical basis and technical support for monitoring the spread of resistant strains and formulating and optimizing antiretroviral therapy regimens. The study subjects were HIV-1-infected women of childbearing age who were followed up in the county of Liangshan Prefecture from January to September 2023. Peripheral venous blood samples were collected from each subject. The samples were centrifuged to separate the plasma and blood cells for HIV-1 RNA quantitative testing and HIV-1 genotypic drug resistance testing. A total of 47 participants were included in this study. When HIV-1 RNA were <50 copies/mL and between 50 and 1,000 copies/mL, the success rate of HIV-1 DNA pol gene amplification was significantly higher than that of HIV-1 RNA pol gene amplification. Among the 47 subjects, 17 (17/47, 36.17%) indicated successfully amplified HIV-1 RNA and HIV-1 DNA genotypic drug resistance in each region simultaneously, and 9 (9/17, 52.94%) developed any degree of resistance. Among these nine cases, five had consistent resistance, while four indicated inconsistent resistance. Among the five cases with identical drug resistance, there were three cases with inconsistent drug resistance mutations (DRMs). Among the four cases with inconsistent drug resistance results, one had DRMs at the HIV-1 DNA level but no DRMs at the HIV-1 RNA level, while the other three had more DRMs at the HIV-1 RNA level than at the HIV-1 DNA level. The combination of HIV-1 RNA and HIV-1 DNA genotypic drug resistance testing can improve the drawbacks of current single HIV-1 RNA genotypic drug resistance testing, especially when HIV-1 RNA is ≤1,000 copies/mL, and significantly improve the efficiency of HIV-1 genotypic drug resistance testing.

Chronic pain can be complicated by problematic opioid use, which may decrease engagement in care and HIV medication adherence. Pain-related anxiety and catastrophic thinking augment pain severity and interference while driving increased substance use. The acceptability and effect of a music-based smartphone application on negative affect and catastrophic thinking were evaluated in a mixed-methods study among persons living with HIV (PWH) with problematic opioid use and chronic pain. Participants (N = 16) completed a 10-min music listening session, quantitative assessment, and qualitative interview. Paired sample t-tests compared pre- and post-test scores of negative affect (Profile of Mood States-Short Form) and pain catastrophizing (Situational Pain Catastrophizing Scale) before and after music. Qualitative data were analyzed using within-case, across-case analysis. Negative affect significantly decreased after the music listening session (pre 8.3 ± 6.7 vs. post 1.8 ± 2.6; p = .0003), as did pain catastrophizing (pre 8.5 ± 4.3 vs. post 2.5 ± 3.4; p < .0001). Qualitatively, participants (n = 14) viewed the app-based music listening session as acceptable and potentially useful as an intervention or adjuvant for pain management and reduction of opioid use. Overall, a brief exposure to a novel music app produced significant improvements in negative affect and pain-related catastrophic thoughts among PWH with problematic opioid use and chronic pain. Future work should further explore the effects of music on pain and the use of illicit substances more broadly in this population.

Monitoring HIV viral rebound (VR) is crucial, as it indicates an increased risk of infection, transmission, disease progression, and drug resistance. This study aims to identify the association between dynamic VR and historical viral load (VL)/CD4 count measures. A 15-year South Carolina population-based electronic health record data were used for the study. VR was defined as the return of detectable levels of VL (>200 copies/mL) after stable viral suppression (VS) (two consecutive VS, i.e., VL ≤200 copies/mL). A generalized linear mixed model was used to evaluate the association between dynamic VR and historical time-dependent predictors, such as nadir CD4 count and comorbidities, within a year prior to each VR. Subgroup analysis for men who have sex with men (MSM) was also conducted. Among 8,185 people with HIV (PWH), 1,173 (14.3%) had a history of VR. Lower nadir CD4 count (≥500 vs. <200 cells/μL; adjusted odds ratio [aOR]: 0.51, 95% confidence interval [CI]: [0.43, 0.60]), younger age (>60 years old vs. 18-30 years old; aOR: 0.43, 95% CI: [0.29, 0.63]), and being Black (Black vs. White; aOR: 1.58, 95% CI: [1.34, 1.85]) were associated with a higher risk of VR, while MSM (MSM vs. heterosexual; aOR: 0.81, 95% CI: [0.67, 0.96]) were associated with decreased VR risk. The rate of VR among PWH in South Carolina is significant. Within-1-year VL/CD4 test is critical for identifying PWH at risk for VR. Tailored interventions are needed for PWH at risk for VR to achieve sustained suppression and better health outcomes.

Sexual and/or injecting partners of people who inject drugs (PWID) may have an elevated risk of HIV infection either from sharing a transmission network or an epidemiological environment. We estimated the degree of similarity between HIV and hepatitis C (HCV) sequences from PWID and their partners to assess whether partner-based recruitment identifies sexual or injecting partners within transmission networks. We used assisted partner services (APS) to recruit sexual and injecting partners of PWID living with HIV in Kenya and evaluated trends in the TN93 distances (an adjusted measure of sequence similarity) of the HIV-1 and HCV sequences from partner pairs. Of 135 unique pairs identified, 2 sexual, 2 injecting, and 3 unique sexual and injecting partner pairs had HIV sequences within a TN93 distance of 0.045, and 4 unique partner pairs had HCV sequences with distances <0.015. Sexual but not injecting partner pairs had HIV sequences with significantly smaller distances than non-partners, on average, but injecting partner pairs did have significantly smaller HCV-4a patristic distances than non-partners. APS recruitment partly reflects the HIV transmission network among sexual, but not injecting, partners of PWID. The relationship between the injecting partner recruitment and molecular networks is stronger for HCV than HIV and may reflect some recent parenteral HCV transmission. Our results show the importance of continued focus on reducing sexual HIV transmission among PWID and on education and services to address HCV transmission through needle- and/or equipment-sharing.

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.

During male-to-female transmission, HIV-1 must cross the mucosal epithelium of the female reproductive tract to gain access to underlying target cells. Previously, we demonstrated that HIV-1 can penetrate intact columnar and squamous genital epithelia in both ex vivo and in vivo systems. We found that the virus enters the squamous epithelium via a diffusion-based mechanism, but the mechanism of entry in columnar epithelium remained elusive. Using a similar set of approaches, we now demonstrate that HIV enters the endocervical simple columnar epithelium via endocytosis. By exposing human endocervical explant tissue to small molecule endocytosis inhibitors prior to virus exposure, we show that virus penetration into the simple columnar barrier is impeded. These data suggest a transcytosis-based mechanism for HIV-1 penetration into the endocervical columnar barrier.

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.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

When an initial antiretroviral therapy (ART) regimen is effective and well-tolerated, it can be maintained for years as long as the patient adheres. Prior research has revealed that shorter initial ART duration is associated with regimen type, female sex, injection drug use as the HIV transmission category, and lower baseline CD4 count. We examined potential factors associated with initial regimen discontinuation among a subset of newly diagnosed virally unsuppressed PWH in the DC Cohort, an ongoing prospective observation study that uses electronic health record data from clinic sites to collect relevant information, including demographic and clinical information. Participants were excluded from the analysis if they had less than 6 months of follow-up and were virally suppressed at enrollment. There were 479 individuals included in the study. The median age of participants was 33.9 years [interquartile range (IQR) 26-43.9]. The sample was predominantly male (79.1%) and of Black race (70.8%). Over half of the study participants (56.4%) attended community-based clinic sites. The median time to the discontinuation of initial ART was 2.7 years [95% confidence interval (CI): 2.3, 3.4]. Females had a shorter time to ART discontinuation [adjusted hazard ratio (aHR) 1.55, 95% CI: 1.14, 2.11] as did individuals who started on a protease inhibitor-based regimen versus integrase strand transfer inhibitors (aHR 1.87, 95% CI: 1.34, 2.61) and those receiving HIV care at a community-based site (aHR 1.46, 95% CI: 1.11,1.93). Although limited by lack of reason for discontinuation, we demonstrated that ART-naïve women, community clinic attendees, and patients starting on PIs had a shorter duration of initial ART. More anticipatory guidance may be needed to help patients stay on their initial therapy and manage the side effects or to be flexible in trying different regimens.

Transgender women are disproportionately burdened by HIV. Though there is a substantial body of research exploring barriers and facilitators of HIV prevention among transgender women, many barriers remain unaddressed. This study identifies strategies to make HIV prevention trials more congruent with transgender women's preferences and needs to boost trial participation and ultimately enhance initiation and uptake of pre-exposure prophylaxis (PrEP). We conducted in-depth interviews with 15 sexually active, HIV-negative transgender women in New York City to understand: (1) preferences concerning long-acting injectable cabotegravir for PrEP and (2) ideas on how to make HIV prevention trial environments more comfortable. We identified five themes related to increasing transgender women's appeal to trials: (1) creating a more inclusive/welcoming environment, (2) providing compensation that is responsive to transgender women and community needs, (3) centering transgender women in recruitment and informational materials, (4) training study staff on gender-affirming practices, and (5) hiring transgender people as study staff. Participants wanted to see more gender diversity, representation, correct pronouns, gender-affirming practices, and compensation or reimbursements. Together, these practices may improve recruitment and retention of transgender women in HIV prevention trials.