AIDS RESEARCH AND HUMAN RETROVIRUSES

Clinical Benefit of a Conservative Treatment for High-Risk Human Papillomavirus Lesions in Patients with HIV
Hijona Elósegui JJ, Carballo García AL, Fernández Rísquez AC, Presa Lorite JC and Ruiz GF
Infection with Human immunodeficiency virus (HIV) shows a higher risk of infection by Human papillomavirus (HPV). We aim to provide evidence about the effect of a -based vaginal gel (Papilocare®) for treating HPV in women with HIV. Women ≥25 years coinfected by endocervical HPV and with low-grade abnormal cervicovaginal cytology were treated for 6 months with Papilocare® in this observational, prospective, non-controlled pilot study. Cytology, colposcopy, biopsy, hybrid capture test, and 5-point Likert scale were assessed to evaluate cervical lesions repair, HPV clearance, and changes in cervical reepithelization, respectively, at 6 months. Fifteen patients (25-54 years) were included. Overall HPV clearance and cytological normalization rates were 73.3% and 80.0%, respectively, and 55.6% of the abnormal colposcopies were normalized. Re-epithelialization index improved in 66.7% of cases. Papilocare® may be effective for managing endocervical HPV infection in patients living with HIV.
HIV-1 DNA Genotypic Drug Resistance Testing Guides Antiretroviral Therapy in Patients with Low-Level Viremia
Cao B, Liu M, Song S, Guo M, Tang L, Ding P, Yuan T, Wang T and Zhong L
In 2023, we published a case study involving a 10-year-old HIV-1-infected child with low-level viremia (LLV). We showed that this child patient achieved successful viral suppression by modifying the antiretroviral therapy (ART) regimen according to the HIV-1 DNA genotypic drug resistance testing. In this study, we aimed to address whether HIV-1 DNA genotypic drug resistance testing could direct successfully virological suppression in HIV-1-infected patients experiencing persistent LLV based on evidence from a cohort study. The subjects of this study were all people living with HIV-1 who received ART and followed in the Yuexi County (Liangshan, China) from December 2010 to February 2024. From June 2021 to February 2024, a total of 10 mL of peripheral blood was collected from each subject at each follow-up and separated. HIV-1 RNA and HIV-1 DNA were quantified, followed by HIV-1 genotypic drug resistance testing. ART regimens were accordingly adjusted, while follow-up tests were performed in terms of HIV-1 RNA and DNA measurements. The prevalent HIV-1 DNA drug resistance mutations (DRMs) included M184V, K103N, K101E/P, and V108I. The primary resistance mutations observed for nucleoside reverse transcriptase inhibitor (NRTI) were against abacavir, lamivudine, and emtricitabine. For non-NRTI, the primary DRMs were associated with efavirenz and nevirapine. Five out of the six patients were subjected to regimen adjustments according to HIV-1 DNA DRMs, while one patient was continuously treated with unchanged regimen. Viral suppression was achieved in all five ART-changed cases, with observation of remarkable of HIV-1 DNA decline. The ART-unchanged case showed progressive treatment failure with drastic increase of plasma HIV-1 RNA and whole blood HIV-1 DNA. For patients with LLV, HIV-1 DNA genotypic drug resistance testing directed ART regimen considerations are highly recommended for achieving viral suppression.
Confirmation of Two Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Among Men Who Have Sex with Men in Hebei, China
Guan Y, Wang J, Liu M and Lu X
Acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV) is a serious infectious disease because of its' high genetic variability. Nowadays, homosexual contact has become the most predominant transmission route in Hebei province, China, leading to the emergence of novel HIV-1 recombinant forms. The neighbor-joining (N-J) phylogenetic trees were constructed using MEGA 6.0 in order to identify the subtypes of H22063 and H22144. Recombination breakpoints were identified using online resources jpHMM, RIP 3.0, and Simplot 3.5.1. In this study, we identified two novel HIV-1 unique recombinant forms (URFs) _0107 from three men who have sex with men in Hebei province, including H22063 and H22144. The near full-length genome analysis showed H22063 has seven gene recombination sub-regions, including three subtype CRF07_BC gene fragments inserted into the CRF01_AE backbone. H22144 has nine gene recombination sub-regions, including four subtype CRF07_BC gene fragments inserted into the CRF01_AE backbone. This study confirms the emergence of novel recombinant forms and suggests we should strengthen the monitoring of novel HIV recombinant forms in order to deal with the complex HIV-1 epidemiological trend in Hebei province, China.
Identification of a Novel HIV-1 Second-Generation Circulating Recombinant Form (CRF117_0107) in China
Wang X, Zhu B, Li H, Han J, Wang X, Jia L, Zhang B, Li J, Liu Y, Wen H and Li L
Under the background of the main epidemic HIV strains (CRF01_AE and CRF07_BC) co-circulation in China, more HIV second-generation recombinant (SGR) strains with CRF01_AE and CRF07_BC as the backbone were also emerging. In this study, we characterize a novel HIV-1 second-generation circulating recombinant form (CRF117_0107) consisting of CRF01_AE and CRF07_BC fragments from three epidemiologically unrelated HIV-1-infected individuals. One near full-length genome (NFLG) sequence was amplified, sequenced, and spliced in two halves using RNA extracted from the plasma of a homosexual in Shenzhen, Guangdong Province. Two other NFLG sequences were obtained from the Los Alamos HIV Sequence Database under accession numbers KY201177 and MK397789, which were isolated from men who have sex with men (MSM) in Guangdong Province and Zhejiang Province, respectively. Phylogenetic analysis revealed that these NFLG sequences formed a monophyletic cluster with a high bootstrap value of 1.0. Recombination analysis demonstrated that the genome of CRF117_0107 was separated into three segments by two breakpoints. Further subregional phylogenetic analysis was performed that showed segment I+III (790-5990nt, 8295-9412nt) of CRF117_0107 originated from the CRF07_BC cluster, and Segment I+III (5991-8294nt) originated from the CRF01_AE cluster. The appearance of CRF117_0107 further highlights that HIV-1 SGR strains containing CRF01_AE and CRF07_BC will be generated more frequently and will most likely be more conducive to accelerating the spread of HIV in China. This study suggested it's essential to monitor HIV-1 second-generation CRFs among high-risk populations such as MSM for the epidemic and evolution dynamics of HIV-1 in China.
Molecular HIV Surveillance: Beyond Cluster Detection and Response
Mehta SR, Chaillon A, Wells AB and Little SJ
There has been significant controversy surrounding the use of HIV sequence data to identify outbreaks of HIV transmission since the initiation of molecular HIV surveillance (MHS) in the US. The current approach to MHS is comprehensive cluster detection and response (CDR), in which clusters of related infections are identified and used as the basis for cluster-based or population-based interventions. With CDR, there are ethical and stigma concerns around the impingement of individual privacy, as well as legal concerns around the inference of transmission in regions where HIV criminalization laws and statutes exist. Here we propose an alternative approach to the analysis of HIV sequence and public health data that focuses on regions and populations rather than clusters, and still provides useful data for public health agencies.
Sequence Notes: Identification of Three Novel HIV-1 Recombinant Strains with Different Recombination Patterns in Hebei Province, China
Chen S, Shi H, Zhang Z, Yin L, Jia J and Fan W
The global human immunodeficiency virus 1 (HIV-1) pandemic is driven by the extraordinary genetic diversity of the virus, largely resulting from frequent recombination events. These events generate circulating recombinant forms (CRFs) and unique recombinant forms, which significantly contribute to the complexity of HIV-1 epidemiology, especially within key populations, such as men who have sex with men (MSM). Here, we identified three novel HIV-1 recombinant strains consisting of the CRF01_AE and CRF07_BC subtypes from HIV-positive MSM in Baoding City, Hebei Province, China. Using near-full-length genome analysis and phylogenetic reconstruction, the strains-designated BDL017, BDL036, and BDSB006-were shown to exhibit distinct mosaic structures. Each strain contained multiple inserted fragments from CRF07_BC and CRF01_AE within various genomic regions, highlighting their complex recombination patterns. Our study emphasizes the need for continuous molecular surveillance among MSM in Hebei Province to monitor these recombinant forms and prevent their spread to the broader population.
Characterization of an Invisible HIV-1 Circulating Recombinant Form (CRF149_01B) in China
Chen M, Chen H, Dai J, Dong L, Ma Y and Jia M
In this study, by analyzing the available near full-length genome (NFLG) sequences of CRF55_01B, it was found that two of the NFLG sequences could not be clustered with other NFLG sequences. Recombination analysis and phylogenetic analysis suggested that these two NFLG sequences arose by recombination with subtype B based on CRF55_01B, rather than by recombination directly derived from CRF01_AE and subtype B. In addition, two other HIV-1 partial gene fragments found in the database shared the same characteristics as these two NFLG sequences in the key recombination region. These sequences may therefore represent a previously unrecognized circulating recombinant form (CRF), which has been named CRF149_01B. Evolutionary analyses suggested that CRF149_01B emerged between approximately 2005 and 2007. The discovery of CRF149_01B highlights the complexity of HIV recombinant evolution and advances the refinement of the HIV genotyping system. A deeper understanding of HIV-1 genetics will facilitate molecular tracing and provide a basis for studying the biological properties of HIV.
Central Memory CD4 T Cells from Persons with HIV Accumulate DNA Content Defects During Proliferative Response
Romero-Rodríguez DP, Romero-Rodríguez J, Cervantes-Mejía F, Olvera-García G, Pérez-Patrigeon S, Murakami-Ogasawara A, Romero-Mora K, Gómez-Palacio M, Reyes-Terán G, Jiang W and Espinosa E
Central memory (T) cells are a subpopulation of CD4 T cells that sustain overall CD4 T cell counts in HIV infection. The mechanisms underlying their eventual demise, which leads to loss of CD4 T cell counts, are not known. To understand their proneness to death despite their increased movement to proliferation, we examined cell division together with possible cell accumulation in different phases of the cell cycle. Purified circulating T cells from untreated people living with HIV (PLWH) ( = 9) and healthy controls ( = 10) were stimulated using anti-CD3/CD28 agonistic antibodies plus IL-2 and cultured for 4 days. Cell viability, DNA content, proliferation, and cyclin A and cyclin B expression were measured. We found that PLWH T cells more frequently had a DNA content lower than G0/G1, compared with controls ( = .043). These cells accumulated with each division. The proportion of cells with sub-G0/G1 DNA content that were cycling (expressing cyclin A) was greater in the PLWH group ( = .003). The percentage of T cells expressing cyclin A+ among those in G0/G1 and was also greater in the PLWH group ( = .043), suggesting arrest before G2/M. While T cells from PLWH can proliferate, during this process some of them accumulate defects in DNA content that are incompatible with viability, suggesting that they could be intrinsically prone to cell cycle-dependent death. This provides a possible mechanism underlying the increased T cell turnover in HIV infection.
Sequence Notes: Characterization of Two Novel HIV-1 Unique Recombinant Forms (CRF01_AE/B) in Hebei Province
Zhang Z, Zhang Y, Meng J, Fan W, Jia J, Chen S and Shi H
Many new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) of human immunodeficiency virus type-1 (HIV-1) have been discovered in populations with multiple circulating HIV-1 genotypes. In this study, we report two novel URFs derived from two HIV-1-positive individuals in Hebei, China, who were infected through homosexual (BDD142) and heterosexual (BDD154) contact. Phylogenetic and recombinant analyses of the two NFLG revealed that they are second-generation recombinant strains originating from the CRF01_AE cluster 4/B and CRF01_AE cluster 5/B strains. The BDD142 viral genome consists of a subtype B fragment inserted into a CRF01_AE backbone, whereas the BDD154 virus genome consists of two subtype B fragments inserted into a CRF01_AE backbone. Prompt monitoring of molecular epidemiological shifts of HIV-1 within sexually transmitted populations and enhanced behavioral interventions targeting this group are imperative to mitigate the spread of HIV-1 effectively.
Near Full-Length Genomic Characterization of a Novel HIV-1 Unique Recombinant (A1/D/K) from an Immigrant Worker in China Using Nanopore Sequencing
Wang H, Huang H, Li W, Yuan C, Su Y, Zhou X, Chen X and Huang Y
Recombination contributes substantially to the genetic diversity of HIV-1. Here we reported a novel HIV-1 recombinant detected from a Chinese labor who had been to Uganda as an immigrant worker using nanopore sequencing. Near full-length genome (NFLG) phylogenetic analysis showed that the novel HIV-1 recombinant HIV-sd1801 stood in a distinct branch between the CRF130_A1B/CRF131_A1B and CRF50_A1D/CRF84_A1D reference sequences. Recombinant analysis showed that the NFLG of HIV-sd1801 was composed of subtypes A1, D, and K, with 19 recombinant breakpoints observed in the and regions. This is the first detection of a novel HIV-1 recombinant (A1/D/K) in immigrant workers in China, which indicated the continuous evolution of HIV-1 among this population and underscored the importance of continuous surveillance of the dynamic changes of HIV-1.
Comparison of HIV-1 RNA and HIV-1 DNA Genotypic Drug Resistance Testing in Women of Childbearing Age Infected with HIV-1 in Liangshan Prefecture
Cao B, Liu M, Song S, Ding P, Huang F, Huang Y, Zou Y and Zhong L
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 gene amplification was significantly higher than that of HIV-1 RNA 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.
The rs1799884 Gene Polymorphism Modulates Susceptibility to HIV Status and CD4 Cell Count and Viral Load before and After Treatment in AIDS Progressors
Hilmi S, Ouladlahsen A, Bencharki B, Haddaji A, Jebbar S, Bensghir R, Sodqi M, Marih L, Marhoum El Filali K, Benjelloun S and Ezzikouri S
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 gene () 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 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 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; = .001]. However, the TT genotype conferred protection against HIV in a recessive model (OR = 0.50; 95% CI = 0.28-0.91; = .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; = .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; < .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 gene may influence susceptibility to HIV status, progression to AIDS, and response to treatment.
Willingness to Switch to Long-Acting Injectable Cabotegravir and Rilpivirine Every 2 Months for People Living with HIV in Nanjing, China
Li M, Guan H, Zhong M, Di X, Yu N, Chen C, Cai R and Wei H
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 []: 2.990; 95% confidence interval []: 1.171-7.636) was positively associated with willingness to switch, whereas the age of ≥60 (: 0.142; 95% : 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.
Transcytosis as a Mechanism of HIV-1 Entry into Columnar Epithelial Explants of the Female Reproductive Tract
Carias AM, Anderson M, McRaven M, Allen E, Fought AJ and Hope TJ
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 and 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.
Association Between Dynamic Viral Rebound and Longitudinal Measures of Viral Load/CD4 Counts Among People with HIV in South Carolina
Ma Y, Zhang J, Xiao J, Yang X, Weissman S, Li X and Olatosi B
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.
Using HIV and Hepatitis C Molecular Epidemiology to Investigate Assisted Partner Services Recruitment Among People Who Inject Drugs in Kenya
Kingston H, Chohan BH, Mbogo L, Bukusi D, Monroe-Wise A, Sambai B, Omballa V, Tram KH, Guthrie B, Giandhari J, Masyuko S, Bosire R, Sinkele W, de Oliveira T, Scott J, Farquhar C and Herbeck JT
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.
Acceptability of a Smartphone-Based Music Intervention for Chronic Pain and Problematic Opioid Use Among People with HIV: A Mixed-Methods Pilot Study
Goodman GR, Overstreet DS, Wilson JM, O'Cleirigh C, Boyer EW, Meints SM, Taylor SW, Mayer KH, Schreiber KL and Chai PR
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 ( = 16) completed a 10-min music listening session, quantitative assessment and qualitative interview. Paired sample -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; = .0003), as did pain catastrophizing (pre 8.5 ± 4.3 vs. post 2.5 ± 3.4; < .0001). Qualitatively, participants ( = 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.
Genetic Characterization of HIV-1 Gene from Virologically Controlled Aging Individuals with HIV on Long-Term Antiretroviral Therapy
Kummet N, Mishra N, Diaz A, Cusick N, Klotz S and Ahmad N
Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4 T-cells. We, therefore, characterized the gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV) on long-term ART and improved CD4 T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV were used to amplify gene by polymerase chain reaction followed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each HIV sequences were confined to their own subtrees and well discriminated from other HIV sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these individuals' sequences, which decreased with increasing CD4 T counts in these HIV. Most HIV Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding, and nuclear localization. Furthermore, Tat-deduced amino acid sequences showed variation in previously characterized cytotoxic T lymphocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic variability and conservation of functional domains and variations in CTL epitopes were the features of sequences that may be contributing to viral persistence in these 20 aging individuals with HIV on long-term ART.
Exploring the Role of Gut Vascular Barrier Proteins in HIV-Induced Mucosal Damage: A Comparative Study
Jin L, Hu R, Qing Y, Rang Z and Cui F
This study aims to compare intestinal mucosal damage and the expression levels of occludin, zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, β-catenin, and plasmalemma vesicle-associated protein (PLVAP) in the gut vascular barrier (GVB) among people living with HIV (PLWH), asymptomatic PLWH, and healthy volunteers (non-PLWH). Three groups were selected for the study: PLWH, asymptomatic PLWH, and healthy volunteers. Colonic mucosal tissue samples were collected via colonoscopy from all participants. Histological examination of the colonic mucosa was conducted using hematoxylin and eosin staining. The expression levels of occludin, ZO-1, VE-cadherin, β-catenin, and PLVAP were assessed using RT-qPCR, immunohistochemistry, and western blot analyses. Pathological scores of colonic mucosa in PLWH and asymptomatic PLWH were significantly higher than those in non-PLWH ( < .001 and = .0056, respectively). CD4 T cell counts in asymptomatic PLWH and non-PLWH were significantly higher than in PLWH ( < 0.05). The CD4/CD8+ T cell ratio in non-PLWH significantly exceeded those in PLWH and asymptomatic PLWH ( < .05). Analysis of protein and mRNA expression revealed: (1) no statistically significant differences in PLVAP-mRNA expression across all groups ( > .05); (2) higher PLVAP protein levels in PLWH compared with asymptomatic PLWH and non-PLWH ( < .05), with no significant differences between asymptomatic PLWH and non-PLWH ( = .632); (3) significantly higher PLVAP expression in the colonic mucosa of PLWH and asymptomatic PLWH compared with non-PLWH ( = .034 and = .011, respectively), with no significant differences between PLWH and asymptomatic PLWH ( > .999). ZO-1 expression was significantly lower in PLWH than in non-PLWH ( = .012), with no notable differences between asymptomatic PLWH and other groups. PLWH, compared with healthy controls, exhibit significant inflammatory changes in the intestinal mucosa. PLVAP expression serves as a potential indicator to assess the extent of GVB damage and disease progression in PLWH.
The Risk Factors of High-Risk Human Papillomavirus Susceptibility and Clinical Features in HIV-Positive Patients with Anal Condyloma Acuminatum: A Retrospective Cohort Study
Huang S, Qing Y, Deng Y and Deng L
Anal condyloma acuminatum (ACA) has a high incidence and recurrence rate in people living with human papillomavirus (HPV) (PWH) but there are few studies to systematically characterize its clinical features. We aimed to analysis the clinical features in PWH with ACA and elucidate the risk factors of high-risk HPV infection. In total, 208 patients who had ACA surgically excised were enrolled (including 123 ACA subjects with HIV infection) from December 1, 2020, to June 31, 2023, and the sex, age, occupation, marital status, new versus recurrent, HPV genotypes, and treatment history of patients were involved. The HIV viral, CD4 and CD8 cell counts, and the antiretroviral therapy (ART) were also obtained from PWH. PWH with ACA were more likely to be male, employee, and age 19-59 and less likely to be under 18 or over 60 years old ( < .05). The proportion of high-risk HPV infection (30.1%) and triple or more HPV infection (20.5%) in PWH with ACA was significantly higher than those in patients without HIV infection (15.3% and 1.3%, respectively). Moreover, the prevalence of high-risk HPV infection (62.1%) and multiple HPV infection (76.0%) in PWH who were not on ART was significantly higher than those who received ART (20.0%,28.2%, respectively). The conditional logistic regression analysis suggested HIV positivity as the primary risk factor for the high-risk HPV infection in ACA and no ART is a risk factor for high-risk HPV infection. In conclusion, PWH with ACA are more likely to have a high-risk HPV and therefore will be at increased risk for anal SCC, and this risk can in part be mitigated using ART. PWH should start ART as soon as possible after diagnosis. And for PWH with ACA, routine histopathological evaluation and HPV typing of intra-anal warts and follow-up and treatment of all dysplastic warts should be recommended.
Cardiovascular Safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Virologically Suppressed PLWHIV: A Comparative Analysis of CVD Scores
Ciccullo A, Iannone V, Farinacci D, Steiner RJ, Lombardi F, Carbone A, Salvo PF, Baldin G, Borghetti A and Di Giambenedetto S
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, = .021) and the D:A:D score (-0.41, = .012). After 96 weeks, we registered a significant reduction in 10Y-CD calculated via the D:A:D score (-0.98, = .009). Regarding serum lipid markers, after 48 weeks we observed a significant reduction in total cholesterol (-17 mg/dL, < .001), triglycerides (-21 mg/dL, = .015), and LDL cholesterol (-8 mg/dL, = .022). After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, < .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.