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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]

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]

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]

Background: HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART.Methods: From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool.Results: The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013).Conclusions: The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to describe the prevalence, clinical presentation and risk factors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) cases in China.Methods: We performed a descriptive analysis of demographic and clinical data of HIV/TB coinfected patients receiving ART at Beijing Ditan Hospital between January 2014 and October 2018.Results: Of 199 patients included, 45 (22.6%) developed paradoxical TB-IRIS, and 19 (9.5%) TB-IRIS cases presented miliary TB. The pre-ART CD4 count lower than 50 cells/mm3 was found to be significantly associated with development of TB-IRIS. Similarly, patients with higher than 4-fold increase in CD4 cell count after antiretroviral therapy (ART) had significantly higher odds of having TB-IRIS. When patients aged 25-44 years were utilized as the control group, youths (< 25 years old) were more likely to have miliary TB. No significant difference was observed in the intervals from initiation of ART to IRIS presentation between miliary and non-miliary group.Conclusions: In conclusion, our data demonstrate that approximate one quarter of patients coinfected with TB and HIV develop paradoxical TB-IRIS after initial of ART therapy in China. Lower baseline CD4 count and rapid increase in CD4 count are the major risk factors associated with the occurrence of paradoxical TB-IRIS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of AIDS-defining events (ADE) on long-term mortality of HIV positive individuals on antiretroviral therapy (ART), a retrospective HIV/AIDS treatment cohort study performed in Southwestern China. Methods: The retrospective cohort was conducted among 6757 HIV/AIDS patients on ART (2NRTIs + 1NNRTI, 2NRTIs + 1PI and Single or two drugs) recruited in Guigang city, Guangxi, China, from January 2004 to December 2018. Participants were divided into ADE and non-ADE groups, and were followed-up every six months to observe treatment outcomes. Comparison of mortality between groups was performed using the log-rank test and Kaplan–Meier analysis. Cox proportional hazard regression was used to explore the risk factors of mortality. 1:1 propensity score matching (PSM) was used to balance confounding factors and adjust the mortality risk. Results: Of 6757 participants with 29,096.06 person-years of follow-up, 16.86% (1139/6757) belonged to ADE group while the others (83.14%) belonged to the non-ADE group. The most common cause of death by ADE was disseminated mycosis (31.65%), followed by recurrent severe bacterial pneumonia (28.48%), herpes zoster (17.72%), and extra-pulmonary tuberculosis (8.86%). The mortality of the ADE group was significantly higher than that of the non-ADE group [3.45/100 person-years (95% CI 2.92–3.97) vs. 2.34/100 person-years (95% CI 2.15–2.52), P<0.001]. The death risk of the ADE group was also higher than that of the non- ADE group [adjusted hazard ratio (aHR) = 1.291, 95% CI 1.061–1.571, P = 0.011], which was confirmed by PSM analysis (aHR = 1.581, 95% CI 1.192–2.099, P = 0.002). Cox analysis indicated that ADE, older age, male gender, previous non-use of cotrimoxazole, advanced WHO clinical stage, and low baseline CD4+ cell count were the risk factors for death. Conclusions: Even on ART, the mortality risk of HIV positive individuals with ADE was higher than those without ADE. Active testing, earlier diagnosis, and timely therapy with ART may reduce the death risk of ADE. [ABSTRACT FROM AUTHOR]

Background: There are few data on the prevalence of acquired drug resistance mutations (ADRs) in Hunan Province, China, that could affect the effectiveness of antiretroviral therapy (ART). Objectives: The main objectives of this study were to determine the prevalence of acquired drug resistance (ADR) the epidemic characteristics of HIV-1-resistant strains among ART-failed HIV patients in Hunan Province, China. Methods: ART-experienced and virus suppression failure subjects in Hunan between 2012 and 2017 were evaluated by genotyping analysis and mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility. Results: The prevalence of HIV-1 ADR were 2.76, 2.30, 2.98, 2.62, 2.23and 2.17%, respectively, from 2012 to 2017. Overall 2295 sequences were completed from 2932 ART-failure patients, and 914 of these sequences were found to have drug resistance mutation. The most common subtype was AE (64.14%), followed by BC (17.91%) and B (11.50%). Among those 914 patients with drug resistance mutations,93.11% had NNRTI-associated drug resistance mutations, 74.40% had NRTI drug resistance mutations (DRMs) and 6.89% had PI DRMs. Dual-class mutations were observed in 591 (64.66%) cases, and triple-class mutations were observed in 43 (4.70%) cases. M184V (62.04%), K103N (41.90%) and I54L (3.83%) were the most common observed mutations, respectively, in NRTI-, NNRTI- and PI-associated drug resistance. 93.76% subjects who had DRMs received the ART first-line regimens. CD4 count, symptoms in the past 3 months, and ART adherence were found to be associated with HIV-1 DR. Conclusions: This study showed that although the prevalence of HIV-acquired resistance in Hunan Province is at a low-level, the long-term and continuous surveillance of HIV ADR in antiretroviral drugs (ARVs) patients is necessary. [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: As technology progresses, several highly sensitive human immunodeficiency virus (HIV) screening kits are being researched and developed to quickly and efficiently identify serum HIV antibodies within the non-window period. In individuals who are HIV-seronegative, HIV infections that are not within a window period are rare. In such cases, all antibody detection methods will fail, and misdiagnosing these patients will have catastrophic consequences.Case Presentation: A 22-year-old male Chinese patient with diffuse exudative lesions in both lungs and initial symptoms of cough and dyspnoea was diagnosed with Pneumocystis jirovecii pneumonia (PJP) by aetiological examination, and the patient's plasma CD4+ T-cell count was extremely low. In China, PJP is prevalent in HIV-infected individuals. Pneumocystis jirovecii (P. jirovecii) has a high colonisation rate in patients with HIV infections. This patient was naturally suspected of being an HIV patient; however, serum HIV antibody tests were negative using both an enzyme-linked immunosorbent assay (ELISA) and a latex agglutination assay, and HIV was not detected by western blotting. Subsequently, the plasma HIV viral load was found to be extremely high on two repeated plasma HIV RNA tests, thus confirming HIV-seronegative acquired immunodeficiency syndrome (AIDS) in this patient. With administration of effective anti-P. jirovecii treatment and highly active antiretroviral therapy (HAART) after diagnosis, the patient's disease condition was rapidly controlled.Conclusion: This is the second reported case in China of an HIV-seronegative AIDS patient. Such cases are also rare worldwide. Although HIV-seronegative HIV infections are rare, AIDS should be considered in immunodeficient patients with opportunistic infections, even if the test results are HIV-seronegative. Plasma HIV RNA testing is important for such patients. [ABSTRACT FROM AUTHOR]