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Background: With the early initiation of antiretroviral therapy (ART) in China, the demographics of treatment-naïve people living with HIV (PLWH) are moving closer to those of the general population, which is characterized by a gradual increase in metabolic indicators. However, the epidemic trends of overweight and obesity over the past decade in treatment-naïve PLWH ready to initiate ART have not yet been investigated., Methods: A cross-sectional study was conducted, including 12,135 consecutive treatment-naïve PLWH ready to initiate ART in Shenzhen, using data retrieved from the China National Free Antiretroviral Treatment Program database from 2014 to 2020. The chi-square test was used to examine the trends of overweight and obesity between age groups, and multivariate logistic regression was used to identify the association of overweight and obesity with hyperglycemia and dyslipidemia., Results: During the 7-year study period, 12,135 treatment-naïve PLWH ready to initiate ART were included, among whom 1,837 (15.1%) were overweight and 388 (3.2%) were obese. The prevalence of overweight rose from 11.4 to 17.3% ( Z = -4.58, P for trend <0.01) and that of obesity from 2.0% to 4.2% ( Z = -6.45, P for trend <0.01) from 2014 to 2020. The annual prevalence of overweight was the highest in the age group of participants >35 years compared to prevalence in other age groups during the period 2014-2020. Compared with those who were not overweight or obese, PLWH who were overweight or obese were more likely to have hyperglycemia (aOR 1.84, 95% CI: 1.37-2.49 for overweight; aOR 2.68, 95% CI: 1.62-4.44 for obesity), higher ALT level (aOR 2.70, 95% CI: 2.33-3.13 for overweight; aOR 3.85, 95% CI: 2.93-5.05 for obesity), higher TG levels (aOR 1.89, 95% CI 1.63-2.19 for overweight; aOR 2.56, 95% CI 1.97-3.32 for obesity), and lower HDL levels (aOR 1.67, 95% CI 1.44-1.95 for overweight; aOR 2.06, 95% CI 1.54-2.77 for obesity)., Conclusion: The prevalence of overweight and obesity in treatment-naive PLWH increased steadily from 2014 to 2020 in Shenzhen. Overweight and obese in treatment-naive PLWH ready to initiate ART were associated with dyslipidemia and hyperglycemia. Public health authorities should take proactive steps to address these issues by implementing targeted screening, intervention programs including lifestyle modifications, and integrated healthcare services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Sun, He, Zhou, Xu, Zhao, Hu, Wang, Lu and Liu.)

Objectives: In recent years, integrase strand transfer inhibitor (INSTI)-containing regimens have been increasingly adopted in treatment for HIV/AIDS and promoted as non-occupational post-exposure prophylaxis in China. This study aims to describe the prevalence of resistance to integrase and drug resistance mutations (DRMs) among ART-naive patients in Shenzhen, China., Methods: Serum samples and demographic information were collected from newly reported ART-naive patients in Shenzhen in 2020. The study sequenced the coding sequence of the HIV-1 integrase gene and determined the DRMs.​., Results: In this study, 1682 newly reported cases were included and 1071 of them were successfully sequenced finally. The prevalence of primary drug resistance was 1.77%, with 19 samples showing varying degrees of resistance to INSTIs. The study detected six major DRMs in 16 individuals and eight accessory DRMs in 24 individuals. The prevalence of transmitted drug resistance (TDR) mutations was 1.21%, with five transmitted mutations detected in 13 individuals. The prevalence of drug resistance to raltegravir and elvitegravir was statistically higher than to bictegravir, cabotegravir and dolutegravir., Conclusions: The prevalence of INSTI resistance in Shenzhen in 2020 was relatively high. ​Continued surveillance for resistance to INSTIs is recommended and treatment regimens should be adopted based on the pattern of resistance to INSTIs. ​Dolutegravir or bictegravir is first recommended when considering INSTIs as treatment regimens., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: We aimed to examine the evolution of blood lipids and compare the risk of dyslipidemia between antiretroviral-naive people living with HIV who received tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and efavirenz (EFV) (TDF + 3TC + EFV) and those who received coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF)., Methods: We retrospectively reviewed the medical records of 2343 antiretroviral-naive people living with HIV who initiated TDF + 3TC + EFV or E/C/F/TAF. A propensity score matching method was used to compare longitudinal changes of blood lipids between the 2 groups., Results: By using 1:3 matching ratio, we included 253 and 91 matched patients in TDF + 3TC + EFV group and E/C/F/TAF group, respectively. The levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were higher in E/C/F/TAF group than those in TDF + 3TC + EFV group at 3, 6, 9, and 12 months (Wilcoxon test, all Ps < 0.05), except for high-density lipoprotein cholesterol at 9 and 12 months. The cumulative rates of hypercholesterolemia, hypertriglyceridemia, and high LDL-C in PLWH with normal lipid levels in E/C/F/TAF group were higher than those in TDF + 3TC + EFV group (hypercholesterolemia, 59.7% vs 21.5%, P < 0.001; hypertriglyceridemia, 69.5% vs 46.3%, P < 00.001; and high LDL-C, 41.5% vs 14.2%, P < 0.001). Multivariate analysis showed treatment with E/C/F/TAF was associated with a significantly higher risk of hypercholesterolemia [adjusted hazard ratio (HR), 4.12; 95% confidence interval (CI): 2.65 to 6.41], hypertriglyceridemia (adjusted HR, 1.69; 95% CI: 1.18 to 2.43), and high LDL-C (adjusted HR, 4.60; 95% CI: 2.66 to 7.97)., Conclusions: We concluded that treatment with E/C/F/TAF resulted in higher risks of dyslipidemia compared with TDF + 3TC + EFV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Some inpatients with HIV-RNA ≥500,000 copies/mL in China need to use 2-drug regimen for some reasons, although limited data are available for dolutegravir plus lamivudine (3TC) in those patients with ultra-high viral loads., Methods: We conducted a single-center retrospective-prospective study in China and enrolled 42 ART-naive HIV-infected inpatients who use a once-daily 2-drug regimen because of various reasons (drug interaction, renal impairment, age, and other related comorbidities).They were divided into 2 groups, low viral load group (baseline viral load <500,000 copies/mL, n = 20) and high viral load group (baseline viral load ≥500,000 copies/mL, n = 22). All patients were followed up for 48 weeks., Results: The median of baseline viral load was 5.74 log10 copies/mL and CD4+ T-cell count was 59 cells/μL. At week 48, there was no significant difference (P = 0.598) in proportions of participants with HIV-1 RNA <50 copies/mL [90%, 95% confidence interval (CI) (75.6% to 104.4%) in low viral load groups vs 95.5%, 95% CI (86.0% to 104.9%) in high viral load groups]. No differences were found in mean increase of CD4+ T-cell count from baseline between 2 groups (218 ± 122 vs 265 ± 127 cells/μL, P = 0.245). There is no grade 3 or higher treatment-related adverse events and none discontinued treatment because of adverse events., Conclusions: The results of our study in real world support dolutegravir + 3TC dual regimen as a promising therapy option for treatment-naive HIV-infected patient with baseline viral load ≥500,000 copies/mL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Morbidity and mortality of non-AIDS-defining diseases (NADs) have become the increasing burden of people living with HIV (PLWH) with long-term antiretroviral therapy (ART). We aimed to quantify the contribution of modifiable risk factors to NADs. We included PLWHs starting ART at the Third People's Hospital of Shenzhen (China) from Jan 1, 2010 to Dec 31, 2017. We defined NAD outcomes of interest as cardiovascular disease (CVD), end-stage liver disease (ESLD), advanced renal disease (ARD), and non-AIDS-defining cancers (NADCs). We estimated incidence of outcomes and population-attributable fractions (PAFs) of modifiable traditional and HIV-related risk factors for each outcome. Overall, 8,301 participants (median age at study entry, 31 years) contributed 33,146 person-years of follow-up (PYFU). Incidence of CVD (362/100,000 PYFU) was the highest among outcomes, followed by that of ARD (270/100,000 PYFU), ESLD (213/100,000 PYFU), and NADC (152/100,000 PYFU). Totally, 34.14% of CVD was attributable to smoking, 7.98% to hypertension, and 6.44% to diabetes. For ESLD, 24.57% and 25.04% of it could be avoided if chronic hepatitis B and C virus infection, respectively, did not present. The leading PAFs for ARD were declined estimated glomerular filtration rate (eGFR) (39.68%) and low CD4 count (39.61%), followed by diabetes (10.19%). PAFs of hypertension, diabetes, and smoking for CVD, and declined eGFR and diabetes for ARD increased with age. The contribution of traditional risk factors for these NADs far outweighed the HIV-related risk factors. Individual-level interventions and population-level policy-making is needed to focus on these factors to prevent NADs in long-term management of HIV infection.

We investigated changes in CD T cell counts related to sleep quality, depression, anxiety, and sociodemographic variables in heterogeneous groups of people living with HIV in a 6-month prospective study. Our longitudinal study involved 247 ambulatory patients living with HIV and using antiretroviral therapy. Sleep quality, anxiety, depression, and CD T cell counts were assessed three times at 3-month intervals. Growth curve mixture modeling was conducted to explore changes over time. A two-class mixture model with logarithmic change pattern fit the data best. For the majority of the sample (89.1%), anxiety, depression, and sleep quality did not change when CD T cells increased. For a small proportion of the sample (11.9%), sleep quality, anxiety, and depression deteriorated when CD T cells decreased. Marital status and alcohol use affected the classification significantly. Health care professionals should provide relevant services to people living with HIV with decreasing CD T cell counts.

Background: We recently identified a novel alternatively spliced isoform of human programmed cell death 1 (PD-1), named Δ42PD1, which contains a 42-base-pair in-frame deletion compared with the full-length PD-1. Δ42PD1 is likely constitutively expressed on human monocytes and down-regulated in patients infected with human immunodeficiency virus type 1 (HIV-1). The mechanism underlying the regulation of Δ42PD-1 expression in monocytes remains unknown., Methods: By flow cytometry, we investigated the effect of Interferon-gamma (INF-γ) on the expression of Δ42PD1 in primary human monocytes as well as monocytic cell lines THP-1 and U937 cells. In addition, signaling pathway inhibitors and Δ42PD1-specific blocking antibody were used to explore the pathway involved in INF-γ-induced Δ42PD1 upregulation, and to elucidate the relationship between Δ42PD1 and TNF-α or IL-6 production by INF-γ primed monocytes in response to pre-fixed E. coli. Furthermore, we assessed T-cell proliferation, activation and cytokine production as enriched CD4 + T cells were co-cultured with THP-1 or U937 cells, with or without Δ42PD1-blocking antibody., Results: Treatment of human peripheral blood mononuclear cells (PBMCs) with IFN-γ resulted in an approximately 4-fold increase in the expression of Δ42PD1 on monocytes. Similarly, IFN-γ upregulates Δ42PD1 expression on human monocytic cell lines THP-1 and U937, in a time- and dose-dependent manner. IFN-γ-induced Δ42PD1 upregulation was abolished by JAK inhibitors Ruxolitinib and Tasocitinib, PI3K inhibitor LY294002, and AKT inhibitor MK-2206, respectively, but not by STAT1 inhibitor and MAPK signaling pathway inhibitors. JAK, PI3K-AKT, and MAPK signaling inhibitors abolished effectively the production of TNF-α and IL-6 in INF-γ-primed monocytes in response to pre-fixed E. coli. In contrast, Δ42PD1-specific blocking antibody did not affect the IFN-γ-induced priming effect. Furthermore, the MFI ratio of Δ42PD1 to full-length PD-1 (PD-1 Δ/F ratio) was significantly and positively correlated with TNF-α (P =  0.0289, r = 0.6038) produced by circulating CD14 + monocytes in response to pre-fixed E. coli. Notably, Δ42PD1 blockage significantly inhibited CD4 + T-cells proliferation and cytokine production in the co-culture conditions., Conclusions: We demonstrated that IFN-γ increases Δ42PD1 expression on human monocytes via activating the PI3K/AKT signaling pathway downstream of JAKs, and that the PD-1 Δ/F ratio is a potential biomarker to predict the functional state of monocytes. Notably, we revealed the Δ42PD1 play a role in T-cell regulation, providing a novel potential approach to manipulate adaptive immune response., (Copyright © 2019. Published by Elsevier GmbH.)