Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study.

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1. Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening. No formal statistical analyses were performed. Results: Among 272 participants, increases were observed from baseline to week 96 in CD4+ T-cell count (mean increase, +205 cells/mm3) and CD4+/CD8+ ratio (mean increase, +0.24). The proportion of observed participants with a CD4+/CD8+ ratio ≥0.45 increased from 9% (25/272) at baseline to 40% (85/213) at week 96. From baseline to week 96, we also observed trends toward decreases in the following (mean [SD] change): soluble CD14, -738.2 (981.8) µg/L; soluble CD163, -138.0 (193.4) µg/L; and D-dimer, -0.099 (0.521) mg/L fibrinogen-equivalent units. Decreases in biomarkers were generally observed among subgroups by baseline disease characteristics, virologic response, and CD4+ T-cell count. Conclusions: These data suggest that heavily treatment-experienced persons with multidrug-resistant HIV-1 treated with fostemsavir + optimized background therapy may have improvements in immune parameters, including markers of monocyte activation and coagulopathy. Clinical Trials Registration: NCT02362503 (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02362503).

The Prognosis for Delayed Immune Recovery in HIV-Infected Children might be Associated with Pre-cART CD4 + T cell Count Irrespective of Co-Infection with Tuberculosis.

Background: Immune reconstitution following the initiation of combination antiretroviral therapy (cART) significantly impacts the prognosis of individuals infected with human immunodeficiency virus (HIV). Our previous studies have indicated that the baseline CD4+ T cells count and percentage before cART initiation are predictors of immune recovery in TB-negative children infected with HIV, with TB co-infection potentially causing a delay in immune recovery. However, it remains unclear whether these predictors consistently impact immune reconstitution during long-term intensive cART treatment in TB-negative/positive children infected with HIV. Results: We confirmed that the baseline CD4+ T cell count is a significant predictor of immune recovery following long-term intensive cART treatment among children aged 5 to 18 years. Children with lower CD4+ T cell count prior cART initiation did not show substantial immunological recovery during the follow-up period. Interestingly, children who were co-infected with TB and had higher baseline CD4+ T cell count eventually achieved good immunological recovery comparable to the TB-negative HIV-infected children. Hence, the baseline CD4+ T cell count at the onset of treatment serves as a reliable predictor of immunological reconstitution in HIV-infected children with or without TB co-infection. Taken together, this follow-up study validates our previous findings and further establishes that initiating cART early alongside early HIV testing can help prevent the diminished CD4+ T cell count associated with inadequate immunological reconstitution.

Improving 1-Year Mortality Following Intensive Care Unit Admission in Adults with HIV: A 20-Year Observational Study.

BACKGROUND: Despite widespread use of combination antiretroviral therapy, people with HIV (PWH) continue to have an increased risk of admission to and mortality in the intensive care unit (ICU). Mortality risk after hospital discharge is not well described. Using retrospective data on adult PWH (≥18 years) admitted to ICU from 2000-2019 in an HIV-referral centre, we describe trends in 1-year mortality after ICU admission. METHODS: One-year mortality was calculated from index ICU admission to date of death; with follow-up right-censored at day 365 for people remaining alive at 1 year, or day 7 after ICU discharge if lost-to-follow-up after hospital discharge. Cox regression was used to describe the association with calendar year before and after adjustment for patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation II [APACHE II] score, CD4+ T-cell count, and recent HIV diagnosis) at ICU admission. Analyses were additionally restricted to those discharged alive from ICU using a left-truncated design, with further adjustment for respiratory failure at ICU admission in these analyses. RESULTS: Two hundred and twenty-one PWH were admitted to ICU (72% male, median [interquartile range] age 45 [38-53] years) of whom 108 died within 1-year (cumulative 1-year survival: 50%). Overall, the hazard of 1-year mortality was decreased by 10% per year (crude hazard ratio (HR): 0.90 (95% confidence interval: 0.87-0.93)); the association was reduced to 7% per year (adjusted HR: 0.93 (0.89-0.98)) after adjustment. Conclusions were similar among the subset of 136 patients discharged alive (unadjusted: 0.91 (0.84-0.98); adjusted 0.92 (0.84, 1.02)). CONCLUSIONS: Between 2000 and 2019, 1-year mortality after ICU admission declined at this ICU. Our findings highlight the need for multi-centre studies and the importance of continued engagement in care after hospital discharge among PWH.

Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

Distinct genetic clusters in HIV-1 CRF01_AE-infected patients induced variable degrees of CD4+ T-cell loss.

CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4+ T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types. Their mechanisms of pathogenicity were evaluated by co-receptor tropisms, predicted by genotyping and confirmed with virus isolate phenotyping, as well as inflammation parameters. Our research elucidated that individuals infected with CRF01_AE clusters 1 and 2 exhibited significantly lower baseline CD4+ T-cell counts and greater CD4+ T-cell loss in cohort follow-up, compared with other HIV-1 sub-types and CRF01_AE clusters. The increased pathogenesis of cluster 1 or 2 was associated with higher CXCR4 tropisms, higher inflammation/immune activation, and increased pyroptosis. The protein structure modeling analysis revealed that the envelope V3 loop of clusters 1 and 2 viruses is favorable for CXCR4 co-receptor usage. Imbedded with the most mutating reverse transcriptase, HIV-1 is one of the most variable viruses. CRF01_AE clusters 1 and 2 have been found to have evolved into more virulent strains in regions with predominant heterosexual infections. The virulent strains increased the pressure for early diagnosis and treatment in HIV patients. To save more lives, HIV-1 surveillance systems should be upgraded from serology and genotyping to phenotyping, which could support precision interventions for those infected by virulent viruses. IMPORTANCE: Retroviruses swiftly adapt, employing error-prone enzymes for genetic and phenotypic evolution, optimizing survival strategies, and enhancing virulence levels. HIV-1 CRF01_AE has persistently undergone adaptive selection, and cluster 1 and 2 infections display lower counts and fast loss of CD4+ T cells than other HIV-1 sub-types and CRF01_AE clusters. Its mechanisms are associated with increased CXCR4 tropism due to an envelope structure change favoring a tropism shift from CCR5 to CXCR4, thereby shaping viral phenotype features and impacting pathogenicity. This underscores the significance of consistently monitoring HIV-1 genetic evolution and phenotypic transfer to see whether selection bias across risk groups alters the delicate balance of transmissible versus toxic trade-offs, since virulent strains such as CRF01_AE clusters 1 and 2 could seriously compromise the efficacy of antiviral treatment. Only through such early warning and diagnostic services can precise antiviral treatments be administered to those infected with more virulent HIV-1 strains.

Associations Between HIV and Severe Mpox in an Atlanta Cohort.

BACKGROUND: In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). METHODS: We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. RESULTS: Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01-6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00-4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. CONCLUSIONS: PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.

Efficacy and safety of hypertonic dextrose prolotherapy for patients with post-herpetic neuralgia / 上海交通大学学报（医学版）

Objective·To investigate the efficacy and safety of hypertonic dextrose prolotherapy(DPT)in the treatment of postherpetic neuralgia.Methods·Seventy-eight patients with postherpetic neuralgia who visited the Department of Pain of The Affiliated Hospital of Xuzhou Medical University from June 2019 to December 2022 were selected.The patients were randomly assigned to a control group and a research group in a 1∶1 ratio,with 39 patients in each group.The control group was treated with traditional analgesic solution,while the research group was treated with traditional analgesic solution combined with DPT.Visual analog scale(VAS)was used to evaluate the patients'pain level before and after treatment,flow cytometry was used to measure the patients'T-cell subsets,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of C-reactive protein(CRP),interleukin-6(IL-6),and IL-10 cytokines.The VAS scores were compared between the two groups of patients before and at 1,2,4,8,and 12 weeks after treatment.CD4+/CD8+,CRP,IL-6,IL-10 levels,and the incidence of adverse reactions before and 2 weeks after treatment were compared between the two groups.Results·There was no statistically significant difference in sex ratio,age,and disease duration between the two groups of patients.The VAS scores of the two groups of patients at 1,2,4,8,and 12 weeks after treatment were significantly lower than those before treatment,and the differences were statistically significant(all P<0.05).The VAS scores of the research group at 1,2,4,8,and 12 weeks after treatment were significantly lower than those of the control group(all P<0.05).There was no statistically significant difference in basal CD4+/CD8+,CRP,IL-6 and IL-10 levels between the two groups of patients.IL-6 and CRP levels in the research group were significantly lower after treatment than those in the control group,and the differences were statistically significant(all P=0.000).CD4+/CD8+ and IL-10 levels were significantly higher in the research group than those in the control group after treatment,and the difference was statistically significant(all P=0.000).No adverse reactions such as local nerve damage,epidural hematoma,infection,pneumothorax or allergy occurred in both groups of patients during the treatment.Conclusion·DPT can significantly reduce the pain of PHN patients,improve patients'T lymphocyte subpopulations and cytokine expression,and can be safely applied to the clinic.

Immunologic and Virologic Parameters Associated With Human Immunodeficiency Virus (HIV) DNA Reservoir Size in People With HIV Receiving Antiretroviral Therapy.

BACKGROUND: A better understanding of the dynamics of human immunodeficiency virus (HIV) reservoirs in CD4+ T cells of people with HIV (PWH) receiving antiretroviral therapy (ART) is crucial for developing therapies to eradicate the virus. METHODS: We conducted a study involving 28 aviremic PWH receiving ART with high and low levels of HIV DNA. We analyzed immunologic and virologic parameters and their association with the HIV reservoir size. RESULTS: The frequency of CD4+ T cells carrying HIV DNA was associated with higher pre-ART plasma viremia, lower pre-ART CD4+ T-cell counts, and lower pre-ART CD4/CD8 ratios. During ART, the High group maintained elevated levels of intact HIV proviral DNA, cell-associated HIV RNA, and inducible virion-associated HIV RNA. HIV sequence analysis showed no evidence for preferential accumulation of defective proviruses nor higher frequencies of clonal expansion in the High versus Low group. Phenotypic and functional T-cell analyses did not show enhanced immune-mediated virologic control in the Low versus High group. Of considerable interest, pre-ART innate immunity was significantly higher in the Low versus High group. CONCLUSIONS: Our data suggest that innate immunity at the time of ART initiation may play an important role in modulating the dynamics and persistence of viral reservoirs in PWH.

Immune indices and oral health in patients infected with the human immunodeficiency virus.

BACKGROUND: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). During the incubation period of AIDS, oral manifestations may precede systemic symptoms; therefore, it is vitally important to explore the relationship between HIV and oral health and other indicators. This study aimed to further assess the correlation between demographic risk factors, the dental health of HIV-infected patients, and the correlation of oral health indicators with CD4+ T-cell counts (CTCCs) and HIV viral loads (HIV-VLs). METHODS: Demographic data on 108 HIV-infected patients were first recorded by questionnaire from March 2016 to November 2018. Patients' dental health and oral lesions were assessed by a dental specialist; in addition, they were tested for CTCCs and HIV-VLs by flow cytometry and NucliSENS EasyQ® HIV-1 virometer. Finally, the links between CTCC, HIV-VL, and the dental health (including oral lesions) of the patients were analyzed. RESULTS: We found that age, marital status, and body mass index (BMI) were relevant to the patient's dental health (P < 0.05) and that their oral hygiene was relevant to their dental health (P < 0.05). However, HIV-VL was not directly related to periodontal/dental clinical indicators (P > 0.05). We discovered that the oral lesions in HIV-infected patients were related to decreased CTCCs and increased HIV-VLs (P < 0.05). CONCLUSIONS: We concluded that HIV-infected patients with severely impaired immune function tend to have poor dental health. Moreover, the prevalence of oral lesions was negatively correlated with CTCC and positively correlated with HIV-VL.

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1.

INTRODUCTION: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. METHODS: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety. RESULTS: At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm3 (RC) and 240 cells/mm3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm3). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident. CONCLUSION: Through ~5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02362503.

Antibody response to the third dose of inactivated COVID-19 vaccine in people living with HIV (PLWH): A longitudinal cohort.

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.

Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma.

Objective: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). Design: Cross-sectional case-control study. Subjects: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. Methods: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-ß1 (TGF-ß1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson's correlation (r) was used to assess correlations. Main Outcome Measures: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. Results: Patients with POAG (visual field mean deviation, -4.7 ± 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9% of POAG and 60.0% of control subjects had prior cataract surgery (P = 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 ± 7.9% vs. 2.6 ± 2.0%, P = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%, P < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2, P = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (P ≥ 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 ± 12.1 pg/ml vs. 10.0 ± 4.3 pg/ml; P < 0.001), but TGF-ß1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient r = -0.31, P = 0.03; r = -0.52, p = 0.002; r = -0.72, P < 0.001, respectively). Conclusions: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection.

BACKGROUND: Efavirenz (EFV)- and dolutegravir (DTG)-based antiretroviral therapy (ART) is the former and current recommended regimen for treatment-naive individuals with human immunodeficiency virus type 1 (HIV-1). Whether they impact the immunological and neuropsychiatric profile differentially remains unclear. METHODS: This retrospective analysis included 258 participants enrolled during acute HIV-1 infection (AHI). Participants initiated 1 of 3 ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included 2 nucleoside reverse-transcriptase inhibitors and were maintained for 96 weeks. CD4+ and CD8+ T-cell counts, mood symptoms, and composite score on a 4-test neuropsychological battery (NPZ-4) were compared. RESULTS: At baseline, the median age was 26 years, 99% were male, and 36% were enrolled during Fiebig stage I-II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared with the EFV group, the DTG group showed greater increments of CD4+ (P < .001) and CD8+ (P = .015) T-cell counts but a similar increment of CD4/CD8 ratio at week 96. NPZ-4 improvement was similar between the 2 groups at week 24 but greater in the DTG group at week 96 (P = .005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the 2 groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group vs the EFV group. CONCLUSIONS: Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4+ and CD8+ T-cell counts and improvement in cognitive performance.

Characteristics and the first CD4+T lymphocyte counts of newly reported HIV-infected cases aged 50 and above in Dehong Prefecture of Yunnan Province during 2016 to 2021 / 上海预防医学

ObjectiveTo investigate the factors that influence the first CD4+T lymphocyte counts in newly reported HIV-infected cases aged 50 and above in Dehong Prefecture of Yunnan Province during 2016 to 2021， and to understand the patient immune status and disease progression so as to provide scientific basis for HIV prevention and control strategies in the future. MethodsData was collected from the national HIV/AIDS information system. Multivariate logistic regression was used for the analysis of factors affecting the first CD4+T lymphocyte counts. ResultsA total of 642 cases of HIV infection were newly reported， among them， 571 cases had CD4+T lymphocyte counts and 200 cases （35.03%） had CD4+T lymphocyte counts <200 cells·μL-1. Patients who were in the 50-59 age group， male， divorced or widowed， and less educated were more likely to have CD4+T lymphocyte counts <200 cells·μL-1. Compared with active testing consultants， forced reeducation through labor or drug rehabilitation cases were less likely to have CD4+T lymphocyte counts <200 cells·μL-1. ConclusionThere is no obvious upward trend in newly reported HIV infected persons aged 50 years and above in Dehong Prefecture during 2016 to 2021. However， the situation of CD4+T lymphocyte counts <200 cells·μL-1 is still serious. Attention should be paid to the key groups： male， Chinese nationality， farmers， Han nationality， married or divorced， junior high school education or below， and heterosexual transmission. It is necessary to strengthen the intervention in people aged 50 and above and improve the detection efficiency.

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma-a retrospective cohort study.

Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4+ T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker. Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes. Results: The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P<0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085). Conclusions: In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Failure to seroconvert after three doses of inactivated COVID-19 vaccines in a patient co-infected with HBV and HIV: A case report.

In the global context of the COVID-19 pandemic, the overall benefits of getting any COVID-19 vaccine approved by the World Health Organization for emergency use outweigh the potential risks, even in people with weakened immune systems, including people living with HIV (PLWH). At present, there are no reports of HIV/hepatitis B virus (HBV) co-infected patients receiving a booster dose of the inactivated COVID-19 vaccine. Here, we describe a patient with HIV/HBV co-infection who did not seroconvert to three doses of the inactivated COVID-19 vaccine.

Immuno-virological status and its associated factors among HIV-positive patients receiving highly active antiretroviral therapy at delgi primary hospital, northwest Ethiopia, 2020/2021: A cross-sectional study.

Background: Highly active antiretroviral therapy (HAART) improves clinical outcomes by suppressing viral replication and allowing immune reconstitution. It also reduces HIV-related complications including morbidity, mortality, and extended hospitalizations for HIV-positive individuals. Regular assessment for antiretroviral treatment response is fundamentally important to address the factors associated with the poor clinical outcome including immunologic failures among HIV-positive patients on HAART. Therefore, this study aimed to investigate the immuno-virological status and describe its determinants among HIV-positive patients receiving HAART at Delgi primary hospital, Northwest Ethiopia. Methods: A hospital-based cross-sectional study was conducted at Delgi primary hospital from October 25th through June 19th 2021 among a total of 442 study participants. A systematic random sampling technique was employed to enrol participants in the study. Socio-demographic and clinically related data were collected using a semi-structured questionnaire. About 3-5 ml of venous blood was collected aseptically for CD4+ T cell count and viral load test. SPSS version 20 software was used for statistical analysis. Bivariate and multivariate logistic regression analyses were conducted to determine the factors associated with immuno-virologic status among HIV-positive patients on HAART. The odds ratio with 95% CI was computed to determine the strength of association. Then, a p-value < 0.05 was considered a statistically significant association. For this study, the results were presented by using frequency summary tables, and texts. Results: Among the total study participants, 283 (64%) were males and the mean age of the study participants was 37 ± 11.5. The overall immunological and virological failure among highly active antiretroviral therapy (HAART) receiving participants was found to be 9.5% (42/442, 95%CI:3.23-15.09) and 12.2% (54/442, 95% CI: 2.81-23.04) respectively. In the multivariate analysis, study participants with age ≥50 years old [AOR = 1.97, p = 0.01, 95%CI (0.02-4.03)], participants having current viral load count greater ≥1000 copies/ml [AOR = 3.97, p = 0.03, 95%CI (1.09-5.01)] and having TB-co-infection [AOR = 2.51, p = 0.05, 95%CI (1.02-7.51)] were statistically associated with increased risk of immunological failure. Similarly, TB-coinfected participants were 1.88 (95%CI = 0.89-10.02) times at greater risk for virological failure. Conclusion: In this study, the magnitude of immuno-virological failure is alarming. This may be shown the need for integrated and substantial commitment to enhancing patient antiretroviral treatment adherence in the study area. Also, regular assessment for antiretroviral treatment response is fundamentally important to address the determinants associated with virological and immunologic failures among HIV-positive patients taking HAART. Furthermore, early initiation of HAART may be imperative to achieve favourable virological suppression and immunological reconstitution.

Analysis of late detection of HIV/AIDS cases aged 50 years and above in Jilin Province / 上海预防医学

ObjectiveTo investigate the late detection of HIV/AIDS cases in the elderly in Jilin Province and analyze its influencing factors， to provide theoretical basis for improving their life quality. MethodsThe first CD4 values of HIV/AIDS patients aged 50 years and above living in Jilin Province were used to estimate late detection， and the influencing factors of late detection in elderly cases were analyzed. ResultsThe average CD4 cell count of newly reported HIV/AIDS cases aged 50 and above in Jilin Province from 1996 to 2021 was （230.55±191.97）， the low value group accounted for the largest proportion （50.8%）， and the late detection rate was 59.3% （1397/2325）. The late detection cases were mainly from sexual transmission （46.8% for same-sex and 48.2% for heterosexual contact）. From the perspective of sample sources， most of the late detection patients were diagnosed while testing for other illnesses， followed by testing and consulting. In terms of contact history， the late detection of cases of men who have sex with men was higher. The binary logistic regression analysis showed that gender， marriage， sample source and report year were the factors affecting the late detection of AIDS. The late detection rate of males was higher， and cases of married couples were more likely to be late detection. With the increase of report year， the late detection rate decreased， and testing and counseling could effectively reduce the late detection rate of AIDS. ConclusionThe CD4 cell count in the first detection of HIV/AIDS in the elderly in Jilin Province is low， and the late detection rate of male cases is high. In recent years， the expansion of voluntary counseling and testing in Jilin Province has effectively reduced the late detection rate of HIV/AIDS. At the same time， sex education should be strengthened for the elderly， healthy marital relationships should be advocated and more attention should be paid to the mental health of the elderly.

Association of CD4 T cell count and optimal timing of antiretroviral therapy initiation with immune reconstitution inflammatory syndrome and all-cause mortality for HIV-infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and meta-analysis.

AIMS: CD4 T cell count and optimal timing of antiretroviral therapy (ART) during tuberculosis (TB) treatment are challenging. We conducted a meta-analysis to assess the association of CD4 T cell count and timing of ART initiation with immune reconstitution inflammatory syndrome (IRIS) and all-cause mortality of patients co-infected with HIV/TB. METHODS: We conducted an electronic search of clinical studies dated from January 1980 to December 2019 in PubMed and EMBASE. Randomized, controlled trials evaluating low-base CD4 T cell count (< 50 cells/µL) versus high-base CD4 T cell count (≥ 50 cells/µL), and/or early ART initiation (1 to 28 days after starting TB treatment) versus delayed ART initiation (≥ 28 days after starting TB treatment) were included. The primary endpoints were all-cause mortality and TB-related immune reconstitution inflammatory syndrome (IRIS-TB). The risk ratio (RR) was calculated as a measure of intervention effect. Mantel-Haenszel method was used to estimate the RR. RESULTS: Ten trials (n = 5226) were conducted in North America, Africa, and Asia. We found that low-baseline CD4 T cell count increased the incidence of TB-associated IRIS (RR, 1.47; 95% CI, 1.24-1.75; I2 = 58%) and all-cause mortality (RR, 2.42; 95% CI, 1.71-3.42; I2 = 41%) compared with high baseline CD4 T cell count, and early ART initiation increased the incidence of TB-associated IRIS compared with delayed ART initiation (RR, 1.80; 95% CI, 1.57-2.07; I2 = 74%). However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74-1.12; I2 = 49%) compared with delayed ART initiation. CONCLUSIONS: The present study demonstrates that low-baseline CD4 T cell count (< 50 cells/µL) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS and all-cause mortality. Early ART initiation (≤ 28 days) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS. However, evidence is insufficient to refute or support a survival benefit conferred by the comparison between early ART initiation (≤ 28 days) and delayed ART initiation.

Predictors of Current CD4+ T-Cell Count Among Women of Reproductive Age on Antiretroviral Therapy in Public Hospitals, Southwest Ethiopia.

BACKGROUND: HIV/AIDS is one of the major global public health problems. CD4 is a glycoprotein found on the surface of different immune cells. CD4 cell counts determine the need for screening and prophylactic interventions against common opportunistic infections in those with advanced HIV disease. Thus, this study aimed to assess the predictors of current CD4+ T-cell count among women of reproductive age on antiretroviral therapy in public hospitals, southwest Ethiopia. METHODS: A cross-sectional study was conducted from February to April 2018. A total of 422 participants in the three public hospitals were selected using a systematic random sampling method. Linear regression analyses were used to determine the important predictors of current CD4+ T-cell count at p-values of <0.05. RESULTS: A total of 422 women with a median age of 37.00 years participated in this study. More than one in ten (12.8%) respondents experienced immunological failure. An increased current CD4+ T-cell count was observed among patients with a tertiary level of education [ß = 56.45, 95% CI (3.5, 109.4)], baseline WHO clinical stage II [ß = 44.06, 95% CI (5.3, 82.9)], initial regimen of AZT+3TC+EFV [ß = 167.23, 95% CI (100.4, 234.1)], with increased baseline CD4+ T-cell count [ß = 0.35, 95% CI (0.2, 0.5)], and with increased time duration on ART [ß = 14.36, 95% CI (6.304, 22.4)]. On the other hand, the current CD4+ T-cell count was lowered among patients with poor baseline adherence, opportunistic infection, and viral load of ≥1000 by 181.06 cells/mm3, 101.62 cells/mm3, and 137.53 cells/mm3 compared to good baseline adherence, no opportunistic infection and undetectable viral load, respectively. CONCLUSION: The immunological failure was relatively low. Maintaining adherence, early identification and treatment of opportunistic infections, and minimizing viral load to undetectable levels may further decrease immunological failure.