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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. [ABSTRACT FROM AUTHOR]

Objective: HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally. Methods: This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran's Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis. Results: Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7–42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2–46.4%) than female (36.5%, 95% CI: 26.9–50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%). Conclusions: Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation. [ABSTRACT FROM AUTHOR]

Background: Despite increasing effort for treating primary central nervous system lymphoma (PCNSL), the prognosis of human immunodeficiency virus (HIV) -related PCNSL was still unsatisfactory. There is currently a lack of clinical evidence for the application of Bruton tyrosine kinase (BTK) inhibitor in HIV-related PCNSL. We reported two HIV-related PCNSL patients, who achieved sustained remission by application of BTK inhibitor based treatment. This protocol had not been previously reported for the treatment of HIV-related PCNSL. Case presentation: The two cases were characterized by the treatment choice of Bruton tyrosine kinase (BTK) inhibitor. Rituximab was not recommended for them due to their very low CD4+ T cell counts. They both took MTX as the first-line therapy and got a relief in initial phase. For the first case, ibrutinib was kept both in the first-line therapy and in the maintenance therapy. When the second case underwent a progressive disease, we continued to use orelabrutinib as one of the salvage treatment, in combination with programmed cell death-1 (PD-1) inhibitor plus lenalidomide. They both achieved a continuous response of up to 20 months without opportunistic infection. Conclusions: This report highlights the safety and effectiveness of BTK inhibitors, as well as lenalidomide and PD-1 inhibitor in HIV-related PCNSL patients. Both the new therapeutic approaches and a multidisciplinary team authentically contributed to improved survival outcome among HIV-positive PCNSL patients. [ABSTRACT FROM AUTHOR]

Background: In 2003, China implemented free antiretroviral therapy (ART) for people living with HIV (PLHIV), establishing an eligibility threshold of CD4 < 200 cells/μl. Subsequently, the entry criteria were revised in 2012 (eligibility threshold: CD4 ≤ 350 cells/μl), 2014 (CD4 ≤ 500 cells/μl), and 2016 (treat-all). However, the impact of treat-all policy on HIV care and treatment indicators in China is unknown. We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China. Methods: Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019, from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China. We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators: monthly proportion of 30-day ART initiation, mean CD4 counts (cells/μl) at ART initiation, and mean estimated time from infection to diagnosis (year). We built separate models according to gender, age, route of transmission and region. Results: Monthly data on ART initiation and collection were available for 75,516 individuals [gender: 83.8% males; age: median 39 years, interquartile range (IQR): 28–53; region: 18.5% Northern China, 10.9% Northeastern China, 17.5% Southern China, 49.2% Southwestern China]. In the first month of treat-all, compared with the contemporaneous counterfactual, there was a significant increase in proportion of 30-day ART initiation [+ 12.6%, incidence rate ratio (IRR) = 1.126, 95% CI: 1.033–1.229; P = 0.007] and mean estimated time from infection to diagnosis (+ 7.0%, IRR = 1.070, 95% CI: 1.021–1.120; P = 0.004), while there was no significant change in mean CD4 at ART initiation (IRR = 0.990, 95% CI: 0.956–1.026; P = 0.585). By December 2019, the three outcomes were not significantly different from expected levels. In the stratified analysis, compared with the contemporaneous counterfactual, mean CD4 at ART initiation showed significant increases in Northern China (+ 3.3%, IRR = 1.033, 95% CI: 1.001–1.065; P = 0.041) and Northeastern China (+ 8.0%, IRR = 1.080, 95% CI: 1.003–1.164; P = 0.042) in the first month of treat-all; mean estimated time from infection to diagnosis showed significant increases in male (+ 5.6%, IRR = 1.056, 95% CI: 1.010–1.104; P = 0.016), female (+ 14.8%, IRR = 1.148, 95% CI: 1.062–1.240; P < 0.001), aged 26–35 (+ 5.3%, IRR = 1.053, 95% CI: 1.001–1.109; P = 0.048) and > 50 (+ 7.8%, IRR = 1.078, 95% CI: 1.000–1.161; P = 0.046), heterosexual transmission (+ 12.4%, IRR = 1.124, 95% CI: 1.042–1.213; P = 0.002) and Southwestern China (+ 12.9%, IRR = 1.129, 95% CI: 1.055–1.208; P < 0.001) in the first month of treat-all. Conclusions: The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes. To advance the work of rapid ART, efforts should be made to streamline the testing and ART initiation process, provide comprehensive support services, and address the issue of uneven distribution of medical resources. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components. Methods: This cross‐sectional investigation included people living with HIV (PLWH) and HIV‐negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components. Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV‐negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18–39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40–59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60–90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06–2.08; and aOR = 1.18, 95% CI: 1.05–1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14–2.28; and aOR = 1.22, 95% CI: 1.09–1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71–1.46; and aOR = 1.06, 95% CI: 0.94–1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described. Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the first line induction chemotherapy cycles for HIV-associated diffuse large B-cell lymphoma (DLBCL) as these are less common than HIV-negative lymphoma. Currently, the optimal treatment cycles option remains undefined. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-associated DLBCL patients in different treatment modes in China. Methods: Totally 273 newly diagnosed HIV-associated DLBCL patients at eleven large academic centers from October 2008 to October 2021, were analyzed. Results: In the entire cohort, the median age was 47 years (range, 21-90) at lymphoma diagnosis, and 223 patients were male (81.7%). One hundred and ninety-four (71.1%) patients were germinal center B-cell-like lymphoma (GCB) subtype. Most patients (65.2%, 178/273) had elevated lactate dehydrogenase (LDH), and advanced Ann Arbor stage (78.9% 213/273) at diagnosis. High international prognostic index (IPI) score (3-5) at diagnosis was found in 65.2% (178/273) of patients. One hundred and fifty-five patients (56.8%) had extranodal involvement. The median CD4 cell count was 168/ml (range, 2-1067), of whom 174 (63.7%) had a CD4 cell count below 200/ml. The median follow-up of our cohort was 10.1 (0.1-160) months. The overall 2-year OS rates 58.0%. Median OS times in the 0, 1-3, 4-6, and >6 cycles chemotherapy cohort were 7.1 months, 20.0 months, not reached, and not reached, respectively (Hazard Ratio (HR) =0.549, 95% Confidence interval (CI) 0.451-0.667; p<0.001). Cox multivariate analysis showed that age ≥60 (HR=2.207, 95%CI 1.321-3.690; p=0.003), high IPI score (3-5) (HR=2.926, 95% CI 1.716-4.988; p<0.001), B symptoms (HR=1.928, 95%CI 1.192-3.119; p=0.007), elevated LDH (HR=1.696, 95%CI 1.031-2.791; p=0.038) and received less than 4 cycles chemotherapy (HR=0.520, 95%CI 0.424-0.637; p<0.001) were independent risk factor for adverse prognosis based on overall survival (OS). Discussion: These results demonstrated that 4-6 cycles chemotherapy were significantly associated with improved outcomes in HIV-associated DLBCL patients. However, >6 cycles chemotherapy did not further improve the survival of patients. [ABSTRACT FROM AUTHOR]

HIV prevalence among men who have sex with men in China has increased dramatically, and timely linkage to care after being diagnosed with HIV is important to treatment success. This cross‐sectional study aims to utilize structural equation modeling to test a hypothesized model of timely linkage to care adapted from the HIV‐related stigma framework. Data were collected from 257 men who have sex with men living with HIV. The proportion of participants with timely linkage to care within 1 month was 63.42%. The model result showed a good fit. Higher HIV‐related stigma was significantly associated with a lower level of social support, mental health, maladaptive coping (three mechanism variables), and attitude toward linkage to care. Higher CD4+ T‐cell count, disclosure of HIV positivity to sexual partners, and greater convenience of accessing care were related to timely linkage to care (p < 0.05). These model results suggest that enhancing attention to family reactions and social support are needed for further research and interventions to accelerate newly diagnosed people's access to HIV care in China. [ABSTRACT FROM AUTHOR]

Background: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV (PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. Methods: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine (Sinopharm, WIBP-CorV, Wuhan Institute of Biological Products Co. Ltd) at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7 days after each injection. The primary immunogenicity outcomes were SARS-CoV-2 neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70. Results: In total, the study included 46 PLWH and 38 HNC who finished 70 days' follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs. HNC (32% and 24%). NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI 3.18–5.87) and 26% (95% CI 14–41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI 10.33–32.33), seroconversion rate (63%, 95% CI 44–79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI 0.119–0.313) and 51% (95% CI 34–69), which was lower than that among HNC [GMEU (0.379 EU/mL, 95% CI 0.224–0.653), seroconversion rate (86%, 95% CI 64–97)]. There were no serious adverse events. Conclusions: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count with effective antiretroviral therapy. [ABSTRACT FROM AUTHOR]