Lack of Resistance Mutations to the Novel HIV-1 Capsid Inhibitor Lenacapavir Among People Living with HIV in Guangdong, China.

Background: The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity. Purpose: To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China. Patients and Methods: A total of 1035 individuals with HIV-1 infection, including 660 highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375 hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gag gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility. Results: Among 1035 samples, 805 gag sequences were amplified, sequenced and assembled successfully from 518 hAART drugs naive individuals and 287 hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN. Conclusion: Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.

Clinical characteristics and prognosis of Talaromycosis marneffei associated immune reconstitution inflammatory syndrome in AIDS patients.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. Few studies elucidated the clinical features and prognosis of Talaromycosis marneffei (TSM)-associated IRIS in HIV/AIDS patients. The aim of our study was to evaluate the incidence, clinical characteristics, and prognosis of TSM-associated IRIS by retrospectively analyzing the clinical data of HIV/AIDS patients with TSM. METHODOLOGY/PRINCIPAL FINDINGS: A total of 224 HIV/AIDS inpatients with TSM were enrolled, aged between 19 and 81 years. Among them, 86.6% were male and 13.4% were female, of which 24 (10.7%) patients developed IRIS. In IRIS group, the median time from ART initiation to IRIS occurrence was 9.0 days (IQR, 5.0-16.8 days), with 87.5% (21/24) occurring within 2 weeks. Primary clinical manifestations included recurrent fever and exacerbation of pulmonary infection. At the onset of IRIS, 54.2% (13/24) patients were treated with intravenous dexamethasone, and 12.5% (5/24) patients were treated with oral prednisone for 1-3 weeks. No significant differences in baseline characteristics or ART regimens were observed between IRIS and non-IRIS groups; however, patients in IRIS group had higher levels of CRP, CD4+ count, and CD4+/CD8+ ratio than non-IRIS group (equivalent time point: 1-2 weeks after ART initiation) at IRIS onset. The IRIS group exhibited longer hospital stays and higher readmission rates, but equivalent mortality rates compared with non-IRIS group. CONCLUSIONS/SIGNIFICANCE: IRIS is a common complication in HIV/AIDS patients with TSM, often occurring within 2 weeks after ART initiation and exhibiting more pronounced immune reconstitution. The occurrence of IRIS significantly extended the hospitalization duration and increased the rate of readmission but had no influence on the mortality rate.

Pretreatment drug resistance among people living with HIV from 2018 to 2022 in Guangzhou, China.

The presence of pretreatment drug resistance (PDR) is posing an increasing threat to HIV control. Here we investigated drug resistance mutations (DRMs) and PDR among 6831 HIV-infected individuals from 2018 to 2022 in Guangzhou, China. DRMs were detected among 24.5% of the patients. The overall prevalence of PDR was 7.4%, with resistance rate to nucleotide reverse transcriptase inhibitor (NRTI) being 1.3%, nonnucleoside reverse transcriptase inhibitor (NNRTI) 4.8%, and protease inhibitor (PI) 1.4%. Abacavir (0.8%) resistance was the most common in NRTI, followed by resistance to emtricitabine (0.6%), lamivudine (0.6%), and tenofovir disoproxil fumarate (0.3%). In NNRTI, nevirapine (3.7%) resistance was the most common, followed by efavirenz (3.5%) and rilpivirine (3.4%). Among PI, resistance to tipranavir (0.8%), nelfinavir (0.6%), fosamprenavir (0.2%) and lopinavir (0.1%) was most frequent. Annual prevalence of PDR showed an increase trend from 2018 to 2022, although not significant. In the multivariable logistic regression model, hepatitis B surface antigen positivity, circulating recombinant form (CRF) 55_01B, CRF08_BC, CRF59_01B, and subtype B were demonstrated as associated risk factors for PDR. The overall prevalence of PDR in Guangzhou was moderate, with relatively severe NNRTI resistance. Therefore, it remains crucial to continue monitoring PDR among newly diagnosed HIV-infected individuals.

ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.

The human immunodeficiency virus type 1 (HIV-1) reservoir consists of latently infected cells which present a major obstacle to achieving a functional cure for HIV-1. The formation and maintenance of HIV-1 latency have been extensively studied, and latency-reversing agents (LRAs) that can reactivate latent HIV-1 by targeting the involved host factors are developed; however, their clinical efficacies remain unsatisfactory. Therefore, it is imperative to identify novel targets for more potential candidates or better combinations for LRAs. In this study, we utilized CRISPR affinity purification in situ of regulatory elements system to screen for host factors associated with the HIV-1 long terminal repeat region that could potentially be involved in HIV-1 latency. We successfully identified that origin recognition complex 1 (ORC1), the largest subunit of the origin recognition complex, contributes to HIV-1 latency in addition to its function in DNA replication initiation. Notably, ORC1 is enriched on the HIV-1 promoter and recruits a series of repressive epigenetic elements, including DNMT1 and HDAC1/2, and histone modifiers, such as H3K9me3 and H3K27me3, thereby facilitating the establishment and maintenance of HIV-1 latency. Moreover, the reactivation of latent HIV-1 through ORC1 depletion has been confirmed across various latency cell models and primary CD4+ T cells from people living with HIV-1. Additionally, we comprehensively validated the properties of liquid-liquid phase separation (LLPS) of ORC1 from multiple perspectives and identified the key regions that promote the formation of LLPS. This property is important for the recruitment of ORC1 to the HIV-1 promoter. Collectively, these findings highlight ORC1 as a potential novel target implicated in HIV-1 latency and position it as a promising candidate for the development of novel LRAs. IMPORTANCE: Identifying host factors involved in maintaining human immunodeficiency virus type 1 (HIV-1) latency and understanding their mechanisms prepares the groundwork to discover novel targets for HIV-1 latent infection and provides further options for the selection of latency-reversing agents in the "shock" strategy. In this study, we identified a novel role of the DNA replication factor origin recognition complex 1 (ORC1) in maintaining repressive chromatin structures surrounding the HIV-1 promoter region, thereby contributing to HIV-1 latency. This discovery expands our understanding of the non-replicative functions of the ORC complex and provides a potential therapeutic strategy for HIV-1 cure.

Clinical characteristics, viral dynamics, and antibody response of monkeypox virus infections among men with and without HIV infection in Guangzhou, China.

Background: Monkeypox virus (MPXV) is spreading globally and nearly half of the infected people were human immunodeficiency virus (HIV) positive. Therefore, an in-depth understanding of the effects of HIV infection on the outcomes of MPXV infection is urgently needed. This study aimed to explore the clinical features, viral dynamics, and antibody response to MPXV infections in men who had sex with men (MSM) with and without HIV co-infection. Design or methods: MPXV-infected patients diagnosed by PCR were recruited in this study and were divided into MPXV and MPXV + HIV groups based on whether they were co-infected with HIV. Clinical data and samples were collected during of the hospital stay and follow up interviews. The symptoms and signs, laboratory examinations, viral shedding in various body fluids or swabs, antibody dynamics were tracked and compared between the two groups. Results: A total of 41 MPXV patients were recruited through June 2023 to September 2023 in Guangzhou. The MPXV group and MPXV + HIV group comprised 20 and 21 MSM, respectively. Patients in the two groups exhibited similar clinical characteristics except for pruritus and eschar, both were significantly fewer in MPXV + HIV group than in MPXV only group. Among the 355 clinical samples collected, MPXV DNA was detected in 100% of scabs, 97.4% of skin swabs, and 92.3% of exudate swabs from lesions, while the positive rate was 87.5% from oropharyngeal swabs, 59% from saliva, 51.3% from anal swabs, 50% from feces, 30.6% from urine samples, 37.5% of semen, and 28.2% from sera. Dynamics analysis revealed that viral DNA was undetectable in most patients 20 days after symptom onset. IgM and IgG antibodies to MPXV were detected in all patients with 3-5 days earlier in the MPXV group than in the MPXV + HIV group. Conclusion: This cohort analysis based on a large outbreak among MSM in Guangzhou indicated no obvious differences in clinical symptoms, viral DNA data, but antibody responses were 3-5 days later in mpox patients with HIV infection.

Severe Organ Impairment Was Common in Elderly Individuals with Dengue in Guangdong, China.

Guangdong, China, has experienced several dengue epidemics involving thousands of confirmed cases in recent decades, and elderly individuals suffered severe dengue (SD) most seriously. However, the clinical characteristics and risk factors for SD among elderly patients in Guangdong have not been investigated. Patients older than 65 years were recruited and divided into a dengue fever (DF) group and an SD group according to the 2009 Dengue Guidelines of the WHO. We analyzed the clinical manifestations of the elderly patients with dengue and then assessed the risk factors for SD. Of a total of 1,027 patients, 868 patients were diagnosed as having DF and 159 as having SD. Of the 159 elderly patients with SD, 129 (81%) had comorbidities, with hypertension being the most common. Severe organ impairment (SOI) (115, 54%) was the most common presentation in SD patients, followed by severe plasma leakage (52, 24.4%) and severe hemorrhage (46, 21.6%). The most common symptom of SOI was kidney injury, followed by heart injury and central nervous system injury. Furthermore, multivariate regression revealed that the presence of chronic obstructive pulmonary disease (COPD), a lower red blood cell (RBC) count (≤3.5 × 1012/L; odds ratio [OR], 0.35; 95% CI, 0.17-0.55; P <0.001), lower serum albumin (ALB) (≤35 U/L; OR, 0.18; 95% CI, 0.09-0.32; P <0.001), and hyperpyrexia (body temperature ≥39°C; OR, 1.8; 95% CI, 1.2-2.6, P <0.001) were risk factors for SD. Severe organ impairment was the predominant manifestation in elderly individuals with SD characterized by kidney injury. The potential risk factors of SD such as presence of COPD and hyperpyrexia and lower RBC and ALB levels might help clinicians identify patients with SD early.

Measuring HBV pregenomic RNA may be a potential biomarker to determine HBV functional cure in HIV/HBV-co-infected patients with HBsAg loss.

Functional cure of hepatitis B virus (HBV) is an optimal treatment goal for chronic hepatitis B, with the loss of hepatitis B surface antigen (HBsAg) being a crucial indicator. However, the adequacy of HBsAg loss for evaluating functional cure of HBV in patients co-infected with HBV/human immunodeficiency virus (HIV) remains controversial. In this study, we measured HBV pregenomic RNA (pgRNA), a potential biomarker that correlates with covalently closed circular DNA, in the frozen plasma of 98 patients with HBsAg loss from a large HIV/HBV co-infection cohort in Guangzhou, China. HBV pgRNA was still detected in 43.9% (44/98) of the patients, suggesting active HBV replication in individuals with HBsAg loss. Our observations imply that HBsAg loss may not be a reliable predictor of HBV functional cure in cases of HIV/HBV co-infection.

Effectiveness of integrase strand transfer inhibitors among treatment-naive people living with HIV/AIDS in Guangdong, China: A real-world, retrospective cohort study.

Integrase strand transfer inhibitors (INSTIs) in anti-retroviral therapy (ART) have been recommended by the World Health Organization for their higher efficacy, favorable safety and tolerability. However, the clinical evidence supporting switching to INSTI-containing regimens in low-and-middle-income countries (LMICs) is limited, as few patients have access to these regimens. We aimed to assess the effectiveness of INSTI-containing regimens in real-world settings in China compared to government-provided free ART. We compared the short-term (first 4 mo following ART initiation) and long-term (1 year after ART initiation) effectiveness between INSTI-containing regimens and free ART drugs provided by the Chinese government in 4 dimensions: viral suppression status, immune response, liver and kidney function, and AIDS-related diseases. We obtained data from electronic medical records in the National Infectious Disease Surveillance System. To control baseline confounders, we used propensity score matching (PSM), calculated using logistic regression including socio-demographic and baseline factors. Among 12,836 patients from 2012 to 2019, 673 (5.2%) used INSTI-containing regimens. Patients with INSTI-containing regimens were matched to those with free drugs (644 vs 644). For short-term effectiveness, patients initiating INSTI-containing regimens were more likely to achieve viral suppression (81.4% vs 52.0%; P < .001). The differences in immune response, liver and kidney function and AIDS-related diseases were not significant between the 2 groups. For long-term effectiveness, viral suppression rates were similar (87.96% vs 84.59%; P = .135), with no significant differences in immune response, liver and kidney function, or AIDS-related diseases. Our study suggests that patients initiating ART with INSTI-containing regimens have worse physical status at baseline than patients starting with free ART drugs. Furthermore, we found better virological performances of INSTI-containing regimens in the short-term but not in the long-term due to a high rate of drug changes. Our findings have clinical implications and provide new evidence regarding the effectiveness of INSTI-containing regimens in LMICs.

Exploring the relationship between illness perception, self-management and quality of life among HIV-positive men who have sex with men.

AIMS: This study aimed to explore the mediating effect of self-management (SM) on the relationship between illness perception and quality of life (QOL) among Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). DESIGN: A cross-sectional study. METHODS: We explored the effect of illness perception and self-management on QOL using the multiple regression model. Moreover, we conducted a simple mediation analysis to examine the role of SM in the relationship between illness perception and QOL. In addition, a parallel mediation analysis was performed to investigate the differences in domains of SM on the relationship between illness perception and QOL. RESULTS: Among 300 Chinese HIV-positive MSM, the mean score of SM was 39.9 ± 6.97, with a range of 14.0-54.0. The higher score in SM indicated a higher level of HIV SM. SM was negatively related to illness perception (r = -0.47) while positively related to QOL (r = 0.56). SM partially mediated the relationship between illness perception and QOL, accounting for 25.3% of the total effect. Specifically, both daily self-management health practices and the chronic nature of the self-management domain played a parallel role in mediating the relationship between illness perception and QOL. CONCLUSION: Our study demonstrated that SM was a significant factor influencing QOL among HIV-positive MSM. Focusing on daily self-management health practices and the chronic nature of self-management could be the potential key targets for enhancing HIV self-management strategies. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study emphasized the role of SM in the well-being of HIV-positive MSM and underscored the importance of developing interventions that integrate SM strategies to improve QOL in this population. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Successful diagnosis of Mycobacterium marinum infection by mNGS in a patient with Human Immunodeficiency Virus: a case report.

INTRODUCTION: Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis caused by other factors clinically. CASE PRESENTATION: Herein, we reported a 68-year-old male patient with Human Immunodeficiency Virus (HIV) who presented redness and swelling in his left hand after being stabbed by marine fish for over 2 months. Mycobacterium tuberculosis infection was considered according to biochemical and pathological examinations, while empirical anti-infection treatment was ineffective. RESULTS: The metagenomic next-generation sequencing (mNGS) detected a large amount of M. marinum sequences, and the patient was finally diagnosed with M. marinum infection. After one month of combination therapy with ethambutol, rifabutin, moxifloxacin, and linezolid, the swelling disappeared significantly. In this case, the successful application of mNGS in diagnosing and treating M. marinum infection has improved the understanding of the microbe both in the laboratory and clinically, especially in patients with HIV. CONCLUSIONS: For diseases with atypical symptoms or difficulty in determining the pathogens, mNGS is suggested in clinical procedures for rapid and accurate diagnosis and treatment.

Molecular genetic characterization analysis of a novel HIV-1 circulating recombinant form (CRF156_0755) in Guangdong, China.

Introduction: The characteristic of human immunodeficiency virus type 1 (HIV-1) is its susceptibility to erroneous replication and recombination, which plays a crucial role in the diverse and dynamic variation of HIV-1. The spread of different subtypes in the same population often leads to the emergence of circulating recombination forms (CRFs). At present, the main recombinant subtypes of HIV-1 in China are CRF07_BC, CRF01_AE, CRF08_BC and B' subtypes, while CRF55_01B has become the fifth major epidemic strain in China after rapid growth in recent years since it was first reported in 2013. In this study, we obtained five nearly full-length genomes (NFLGs) and one half-length genome from five different cities in Guangdong. Here, we focused on analyzing their characteristics, parental origin and drug resistance. Methods: Plasma samples were collected from six HIV-1 infected patients in Guangdong Province who had no epidemiological association with each other. The NFLGs of HIV-1 were amplified in two overlapping segments by the near-terminal dilution method. The positive products were sequenced directly to obtain genomic sequences. The recombinant patterns and breakpoints of the NFLGs were determined using the Simplot software and confirmed by the maximum likelihood trees for segments using the IQ-TREE and BEAST software. The genotypic resistance profiles of the protease reverse transcriptase and integrase were resolved by the Stanford HIV drug resistance database. Results: The six genomes shared highly similar recombinant pattern, with the CRF55_01B backbone substituted by CRF07_BC segments, therefore assigned as CRF156_0755. The evolutionary analysis of the segments showed that CRF07_BC segments were not clustered with the Chinese MSM variants in the CRF07_BC lineage. All the five NFLGs were identified with the non-nucleoside reverse-transcription inhibitors (NNRTIs) resistance mutation V179E. Discussion: With the accumulation and evolution of recombination between CRF55_01B and CRF 07_BC, the prevalence of more recombinant strains of CRF55_01B and CRF 07_BC may occur. Therefore, it is necessary to strengthen the identification and monitoring of the recombination of CRF55_01B and CRF 07_BC.

Identification of a novel HIV-1 third-generation circulating recombinant form (CRF126_0755) in Guangdong, China.

The genetic recombination patterns and genetic distribution of HIV-1 are valuable for elucidating the epidemic and genetic diversity of HIV. Numerous HIV-1 circulating recombinant forms (CRFs) have recently emerged and disseminated rapidly. In China, at least 32 CRFs have been reported to account for more than 80% of all HIV infections. However, CRFs derived from the CRF07_BC and CRF55_01B lineages have never been recorded. Here, a novel third-generation CRF involving HIV-1 was identified in four HIV-1-infected patients in Guangdong, China, who had no epidemiological association with each other. Phylogenetic and recombinant analyses confirmed that these strains shared highly similar recombination patterns, with the CRF07_BC backbone substituted by a CRF55_01B segment; therefore, these strains were classified as CRF126_0755. This is the first study of a CRF derived from CRF07_BC and CRF55_01B. Bayesian phylogenetic inference suggested that CRF126_0755 originated in approximately 2005-2007. The present findings reveal that the genotype composition of HIV-1 has become more complex than that of other viruses and highlight the urgent need for continuous molecular screening and epidemic surveillance within HIV-1-infected populations to advance our understanding of viral transmission mechanisms.

Efficacy and effect on lipid profiles of Ainuovirine-based regimen versus Efavirenz-based regimen in treatment-naïve people with HIV-1 at week 24: A real-world, retrospective, multi-center cohort study.

This study aimed to compare the efficacy and effect on lipid profiles of Ainuovirine (ANV)- and efavirenz (EFV) -based regimens in treatment-naïve people living with HIV-1 (PLWH) at week 24. The proportion of PLWH achieving HIV-1 RNA < the limit of quantification in the ANV group was significantly higher than that in the EFV group (89.18% vs. 76.04%, P = 0.002). The mean change of log10 HIV-1 RNA from baseline was greater (-4.34 vs. -4.18, P < 0.001), the median change from baseline in CD4+ T cell count increased more (106.00 cells/µL vs. 92.00 cells/µL, P = 0.007) in the ANV group, while the CD4+/CD8+ ratio was similar (0.15 vs. 0.20, P = 0.167) between the two groups. The mean changes from baseline in total cholesterol (-0.02 for ANV vs. 0.25 mmol/L for EFV, P < 0.001), triglyceride (-0.14 for ANV vs. 0.11 mmol/L for EFV, P = 0.024), and low-density lipoprotein cholesterol (-0.07 for ANV vs. 0.15 mmol/L for EFV, P < 0.001) was significantly different between the two groups. The percentage of patients with improved lipid profiles was significantly higher in the ANV group (37.44 %) than in the EFV group (29.55%, P = 0.0495). The incidence of any adverse events in the ANV group was significantly lower than that in the EFV group at week 12 (6.2% vs. 30.7%, P < 0.001) and was comparable at week 24 (3.6% vs. 5.5%, P = 0.28). The ANV-based regimen was well tolerated and lipid-friendly in treatment-naïve PLWH.

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study.

Ainuovirine (ANV), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), was approved in China in 2021. In a previous randomized phase 3 trial, ANV demonstrated non-inferior efficacy relative to efavirenz (EFV) and was associated with lower rates of dyslipidemia. In this study, we aimed to explore lipid changes in treatment-experienced people with human immunodeficiency virus (HIV)-1 (PWH) switching to ANV from EFV in real world. At week 24, 96.65% of patients in the ANV group and 93.25% in the EFV group had HIV-1 RNA levels below the limit of quantification (LOQ). Median changes from baseline in CD4 +T cell counts (37.0 vs 36.0 cells/µL, P = 0.886) and CD4+/CD8 +ratio (0.03 vs 0.10, P = 0.360) were similar between the two groups. The ANV group was superior to the EFV group in mean changes in total cholesterol (TC, -0.06 vs 0.26 mmol/L, P = 0.006), triglyceride (TG, -0.6 vs 0.14 mmol/L, P < 0.001), high-density lipoprotein cholesterol (HDL-C, 0.09 vs 0.08 mmol/L, P = 0.006), and low-density lipoprotein cholesterol (LDL-C, -0.18 vs 0.29 mmol/L, P < 0.001) at week 24. We also observed that a higher proportion of patients demonstrated improved TC (13.55% vs 4.45%, P = 0.015) or LDL-C (12.93% vs 6.89%, P = 0.017), and a lower proportion of patients showed worsened LDL-C (5.57% vs 13.52%, P = 0.017) with ANV than with EFV at week 24. In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.

Serum cytokine biosignatures for identification of tuberculosis among HIV-positive inpatients.

BACKGROUND: Serum cytokines correlate with tuberculosis (TB) progression and are predictors of TB recurrence in people living with HIV. We investigated whether serum cytokine biosignatures could diagnose TB among HIV-positive inpatients. METHODS: We recruited HIV-positive inpatients with symptoms of TB and measured serum levels of inflammation biomarkers including IL-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). We then built and tested our TB prediction model. RESULTS: 236 HIV-positive inpatients were enrolled in the first cohort and all the inflammation biomarkers were significantly higher in participants with microbiologically confirmed TB than those without TB. A binary support vector machine (SVM) model was built, incorporating the data of four biomarkers (IL-6, IL-10, TNF-α and IFN-γ). Efficacy of the SVM model was assessed in training (n=189) and validation (n=47) sets with area under the curve (AUC) of 0.92 (95% CI 0.88 to 0.96) and 0.85 (95% CI 0.72 to 0.97), respectively. In an independent test set (n=110), the SVM model yielded an AUC of 0.85 (95% CI 0.76 to 0.94) with 78% (95% CI 68% to 87%) specificity and 85% (95% CI 66% to 96%) sensitivity. Moreover, the SVM model outperformed interferon-gamma release assay (IGRA) among advanced HIV-positive inpatients irrespective of CD4+ T-cell counts, which may be an alternative approach for identifying Mycobacterium tuberculosis infection among HIV-positive inpatients with negative IGRA. CONCLUSIONS: The four-cytokine biosignature model successfully identified TB among HIV-positive inpatients. This diagnostic model may be an alternative approach to diagnose TB in advanced HIV-positive inpatients with low CD4+ T-cell counts.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Genetic characteristics of a novel HIV-1 circulating recombinant form (CRF128_07B) identified among MSM in Guangdong Province, China.

OBJECTIVE: To obtain and investigate the genetic characteristics of four HIV-1 near full-length genome sequences (NFLGs), aiming at a description of a novel circulating recombinant form (CRF) in Guangdong China. METHODS: Plasma samples were collected from HIV-1 infected MSM patients in Guangdong Province who had no epidemiological association with each other. The NFLGs were amplified with two overlapping halves and phylogenetic analyses were performed using Mega V11.0.1. Recombination analyses were comprehensively screened with the jpHMM, RIP, and BootScan analyses. Finally, the Bayesian phylogenetic analyses were performed using Beast V1.10.4 to estimate the origin time. RESULTS: Phylogenetic analyses revealed the four NFLGs formed a distinct monophyletic cluster distinguished from other known subtypes in the Neighbor-joining tree. Recombinant analyses revealed they shared a highly similar recombinant pattern, with the CRF07_BC backbone substituted by three subtype B segments. Subregion phylogenetic analyses confirmed them to be a novel CRF composed of CRF07_BC and subtype B, therefore, designed as CRF128_07B. According to the Bayesian phylogenetic analyses, CRF128_07B was inferred to approximately originated around 2005-2006. CONCLUSIONS: These findings described a novel HIV-1 CRF identified from MSM in Guangdong Province. This is the first detection of a CRF comprising CRF07_BC and subtype B. The present finding highlights the urgent need for continuous molecular screening and the epidemic surveillance within the MSM populations.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Acute facial neuralgia related to initiation of emtricitabine/tenofovir for HIV PrEP: a report of two cases in a PrEP demonstration trial.

BACKGROUND: Emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) fixed-dose combination (FTC/TDF) is generally well-tolerated, although treatment-related adverse events have been reported. METHODS: We report two cases of persons using FTC/TDF PrEP who had acute neuralgia in a Chinese PrEP demonstration trial. RESULTS: Neurological symptoms subsided upon treatment discontinuation. Symptoms were reported as similar to one case's previous experiences with dolutegravir (DTG)+FTC+tenofovir alafenamide (TAF) (for PEP), leading to permanent discontinuation of PrEP. CONCLUSION: Acute facial neuralgia appears to be a rare idiosyncratic adverse event to FTC/TDF.