Association of low-level viremia with mortality among people living with HIV on antiretroviral therapy in Dehong, Southwest China: A retrospective cohort study.

OBJECTIVES: To investigate the association of low-level viremia (LLV) with mortality among people living with HIV (PLHIV) on antiretroviral therapy (ART) in Dehong, Southwest China. METHODS: We analysed data collected from a cohort of PLHIV on ART in Dehong. PLHIV were enrolled in this cohort after they started ART, with viral load (VL) tested once a year afterwards. Each VL level was then categorized into one of the four groups: <50, 50-199, 200-999 and ≥1000 copies/ml. VL levels of 50-199 and 200-999 copies/ml were defined as LLV. The VL level for each participant was re-categorized and fitted into an extended Cox regression model as a time-varying covariate to examine the associations of VL level with all-cause and AIDS-related deaths. RESULTS: Among the included 7273 of 8762 PLHIV in this study, median age (interquartile range, IQR) was 36 (30-43) years and 59.9% were male. The patients were followed up for a median duration (IQR) of 6.2 (4.3-8.2) years. Compared with VL <50 copies/ml, LLV 200-999 copies/ml (adjusted hazard ratio [aHR] and 95% confidence interval [95% CI]: 1.56 [1.04, 2.32]) were associated with elevated risk of all-cause mortality and LLV50-199 (aHR [95% CI]: 1.00 [0.68, 1.45]) were not. Similarly, only LLV200-999 copies/ml (aHR [95% CI]: 2.37 [1.36, 4.14]) corresponded to higher risk of AIDS-related mortality. CONCLUSIONS: This study suggests that PLHIV on ART may have elevated death risks even though the viremia is suppressed at a low level. Interventions targeting PLHIV with LLV should be developed to reduce their mortality.

Microbial translocation is associated with advanced liver fibrosis among people with HIV.

BACKGROUND: The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China. METHOD: A total of 665 people living with HIV were enrolled at baseline and had at least one follow-up visit during the 3-year study period. We calculated the Liver Fibrosis Index (FIB-4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF. RESULTS: Of the participants, 61 (9.17%) had advanced LF (FIB-4 >3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB-4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow-up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR] = 1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR = 1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/µl (aOR = 3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR = 2.52; 95% CI 1.41~4.51) and age >50 years (aOR = 32.66; 95% CI 15.89~66.36). LF progression (increasing FIB-4) was significantly associated with increasing sCD14 level (ß = 1.11; 95% CI 0.97~1.26; p < 0.001) with covariate adjustment. CONCLUSION: The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China.

Incidence and risk factors for acute shoulder pain after hepatectomy: a nested case-control study.

BACKGROUND: Shoulder pain is commonly reported after hepatic surgery; however, the factors affecting post-hepatectomy shoulder pain remain unclear. This study aimed to determine the incidence and risk factors of shoulder pain after hepatectomy. METHODS: This prospective cohort study recruited 218 patients who underwent hepatic resection at our hospital from June to September 2022. Data were obtained from electronic medical records and follow-up assessments on the second postoperative day. All patients denied chronic pain before surgery. In this cohort study, patients were grouped according to the appearance of shoulder pain. Demographic information and perioperative data were compared between the two groups. The relationship between shoulder pain and independent variables was assessed using univariate binary logistic regression analysis. The potential risk factors were analyzed using multivariable binary logistic regression. RESULTS: Of the 218 patients enrolled in this cohort study, 91 (41.7%) reported shoulder pain. Patients in the case group were significantly younger than those in the control group (P = 0.001). Epidural anesthesia was used more frequently in the case group (P = 0.012). Patients over 60 years of age showed a lower incidence of shoulder pain than younger patients (P = 0.028). According to multivariable binary logistic regression analysis, advanced age and epidural anesthesia were associated with risk of shoulder pain (advanced age: odds ratio [OR] [95% confidence interval (CI)]: 0.96 [0.94, 0.99], P = 0.002; epidural anesthesia: OR [95% CI]: 2.08 [1.18, 3.69], P = 0.012). CONCLUSIONS: The incidence of acute shoulder pain after hepatectomy is 41.7%. The application of epidural anesthesia is an independent risk factor for shoulder pain after hepatectomy, whereas advanced age is a protective factor.

Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017.

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.

Risk factors for incident HSV-2 infections among a prospective cohort of HIV-1-discordant couples in China.

OBJECTIVES: Identification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV-1 transmission, particularly among HIV-1-discordant couples. METHODS: A prospective cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province, China. 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis. RESULTS: HSV-2 incidence was 2.9 per 100 person-years (PY) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners. At least 36% of incident HSV-2 infections were from outside sexual partner. Among HIV-1-infected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those with baseline equivocal HSV-2 result, having an initially HSV-2 seropositive or equivocal partner, reporting no sex with study partner and initiating antiretroviral therapy (ART) during follow-up. Among HIV-1-uninfected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner ≥5 times/month, but was lower among those having a partner with baseline CD4(+) count ≥350 cells/µL. CONCLUSIONS: Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population. The relationship between ART initiation and HSV-2 seroconversion requires further investigation.

Occipital Nerve Stimulation for Migraine: A Systematic Review.

Patients who suffer from migraines often report impaired quality of life. Occipital nerve stimulation (ONS) is a novel treatment modality for migraines, although few systematic reviews have evaluated whether this therapy is efficacious. The objective of this study was to evaluate the clinical efficacy and safety of ONS for treating migraine through a literature review. We performed a literature search to identify studies that investigated ONS for migraine treatment. Evidence levels of these studies were assessed by recommendations set by the University of Oxford Centre for Evidence-Based Medicine. Five randomized controlled trials, 4 retrospective studies, and one prospective study met the inclusion criteria. Results from the retrospective studies and case series indicated that ONS significantly reduced the pain intensity and the number of days with headache in patients with migraine. However, the evidence of ONS efficacy established by randomized controlled trials was limited. Improvement in the migraine disability assessment (MIDAS) score was more dramatic than improvement in the SF-36 score at follow-up. The mean complication incidence of ONS was 66% for the reviewed studies. Future clinical studies should optimize and standardize the ONS intervention process and identify the relationship among the surgical process, efficacy, and complications resulting from the procedure.

[Analysis of early detection of HIV infections by provider initiated HIV testing and counselling in regions with high HIV/AIDS epidemic in China].

OBJECTIVE: To understand provider initiated HIV testing and counseling (PITC) in a region with high HIV/AIDS epidemic in China, and analyze its effect to early detection of HIV infections. METHODS: Between January and December, 2013, 37 county level medical institutions were selected as the study sites, among which, 19 were public medical institutions and 18 were private institutions. According to the related regulation, procedures and contents of PITC, the study was implemented among outpatients and inpatients who seek for doctors in these medical institutions and PITC were provided for them. The 'Individual Investigation Form' was used to record the information and high-risky factors, and the respondents were taken venous blood and given HIV screening and confirmation. All available serum samples of newly found HIV/AIDS cases were tested using the BED HIV Incidence Capture Enzyme Immunoassay (BED-CEIA) to differentiate the long-term infections and new infections (early detected infections). Chi-square analysis was used to compare the differences of characteristics of newly infected patients. RESULTS: Between January and December, 2013, a total of 37 medical institutions provided PITC. 55 164 person times were received HIV screening, among which 658 were HIV positive, and 598 were confirmed to be HIV positive. The 598 cases were all provided transferring service. The differences of age, marital status, education levels, transmission routes and testing institutions had statistical significance to early detection (χ(2) equals to 23.54, 10.50, 17.96, 21.22 and 4.80; P equals to < 0.001, 0.005, < 0.001, < 0.001 and 0.029, respectively). And the early detection proportions among patients aged from 20 to 29 and from 50 to 84 were 47.1% (114/242) and 42.1% (24/57), respectively; the proportions among single and married patients were 37.8% (56/148) and 38.9% (143/368), respectively; the proportion among patients with high school education levels were 42.6% (26/61); the proportion among patients transmitted by fixed heterosexual sexual partners was 46.0% (86/187); the proportion among private hospitals was 40.3% (58/144). CONCLUSION: A certain proportion of HIV infections were early detected by PITC in this region. The HIV early detection proportions among specific age group and population with spouse/fixed sexual partners were relatively high.

[A study on the health economic evaluations of prevention of mother-to-child HIV transmission in Dehong prefecture, Yunnan province, China from 2004 to 2013].

OBJECTIVE: To conduct health economic evaluation of the prevention of mother-to-child HIV among pregnant women in Dehong prefecture, Yunnan province, China from 2004 to 2013. METHODS: Data on cost were collected mainly from the annual prevention of mother-to-child transmission (PMTCT) reporting system of Dehong prefecture, and supplemented by HIV PMTCT-related resource allocation data from local health bureau. Effectiveness indexes were from local continuous HIV surveillance system and annual reported data. Cost-effectiveness and cost-utility analysis were used to conduct the health economic evaluation. RESULTS: From 2004 to 2013, 283980 pregnant women were screened for HIV, 2 059 were detected as positive, and the HIV positive rate was 0.73%. The total cost of the PMTCT program was 14 227 000 RMB after discounting, and the unit cost of positive case finding was 4 200 RMB. A total of 26 cases of adults and 325 infants were avoided HIV infection, and the cost-effectiveness ratio (CER) was 40 500 RMB/case. The total obtained quality adjusted life years (QALY) from the program was 8 911.5, each one of which cost 1 600 RMB/QALY. If the feeding pattern were breast feeding, CER would be 42 800 RMB/case and each one of QALY would cost 2 200 RMB. CONCLUSION: Based on the cost-effectiveness and cost-utility analysis, the HIV PMTCT of Dehong prefecture had economic value, which indicates that continued investment is needed to strengthen local HIV PMTCT work.

[Analysis of characteristics and therapy of clients in the extension methadone maintenance therapy clinic].

OBJECTIVE: To understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy. METHODS: From December 20, 2010 to March 10, 2011, the system sampling method was used to get the cases. A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi, Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture, Yunnan province were interviewed, and the demographic characteristics, quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared. A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment. RESULTS: Of the 462 cases, 239 cases were from standard MMT clinic, and 223 cases were from the extension MMT clinic. Among them, 117 cases were new research objects into the group during the investigation. Among the clients of extension MMT clinic, 96.7% (147/152) of them were males, 37.5% (57/152) were Dai nationality, and 61.2% (93/152) were married, 38.8% (59/152) with primary school education, 95.4% (145/152) lived with their family or relatives, 96.7% (147/152) could arrive at the clinic from their habitation within 15 minutes. The positive detection rates 72% (13/18), 71% (24/34), 58% (30/52), 29% (15/52), 14% (6/44), 14% (4/29), 15% (5/34), 17% (6/35), 6% (2/33), 16% (5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ(2) = 61.04, P < 0.05). The period of retention of the clients in extension MMT clinics was 175-days averagely, with an average retention 122 days of when withdrawing. The retention rates of the clients were 52% (37/71)and 61% (28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively. There was no difference in the retention rate between those of two types of clinics (χ(2) = 0.82, P = 0.37) . CONCLUSION: Most of the clients in extension MMT clinics lived with their family or relatives, and spent less time on the way to the clinics. After 9 months methadone maintenance therapy, the quality of life of clients in extension clinics was improved while addiction among them decreased. The extension clinic was an effective strategy for retention in remote areas.

Efficacy of epidural esketamine on postoperative sleep quality after laparoscopic and robotic lower abdominal surgeries: a study protocol for randomised, double-blind, controlled trial.

INTRODUCTION: Postoperative sleep disturbances significantly impair postoperative recovery. The administration of intravenous esketamine has been shown to potentially improve postoperative sleep quality. However, the effectiveness of epidural esketamine in improving postoperative sleep quality remains to be elucidated. This study aims to explore the impact of both intraoperative and postoperative use of epidural esketamine on the postoperative sleep quality of patients undergoing minimally invasive lower abdominal surgeries. METHODS AND ANALYSIS: This randomised, double-blind, parallel-group, placebo-controlled trial will be conducted at the Fudan University Shanghai Cancer Centre. A total of 128 adults undergoing minimally invasive lower abdominal surgeries will be randomly allocated in a 1:1 ratio to either the esketamine group or the placebo group. In the esketamine group, epidural esketamine will be administered intraoperatively (0.2 mg/kg) and postoperatively (25 mg). Postoperatively, all patients will receive epidural analgesia. The primary outcome of the study is the incidence of poor sleep quality on the third day after surgery. The sleep quality assessment will be conducted using the Pittsburgh Sleep Quality Index and a Numeric Rating Scale of sleep. The main secondary outcomes include postoperative pain and anxiety and depression scores. The postoperative pain, both rest pain and movement pain, will be assessed using a Numerical Rating Scale within 5 days after surgery. Anxiety and depression scores will be evaluated using the Hospital Anxiety and Depression Scale both before and after the surgery. Safety outcomes will include delirium, fidgeting, hallucinations, dizziness and nightmares. The analyses will be performed in accordance with intention-to-treat principle ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of the Shanghai Cancer Centre (2309281-9). Prior to participation, all patients will provide written informed consent. The results of the trial are intended to be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300076862.

[Health economic evaluation for the extension clinics of methadone maintenance treatment].

OBJECTIVE: To discuss the cost, cost-effectiveness, and cost-utility of the extension methadone maintenance treatment (MMT) clinics and provide the evidences of the strategy of scaling up the extension MMT clinics. METHODS: A study was conducted in Dehong prefecture, Yunnan province, including Mang, Ruili city, Longchuan, Yingjiang, Lianghe county. 117 newly enrolling heroin addict patients in 17 extension MMT clinics were recruited as subjects from December 2010 to February 2011. An interview was conducted by the trained interviewers for the quality of life score of patients, and the cost of drug use was calculated. Table of outpatient costs of methadone maintenance treatment clinic of Dehong prefecture in Yunnan was used for collecting and calculating the fixed cost, operating cost of the clinics, and the unit cost and incremental cost of the patients from 2008 to 2010. Cost-effectiveness and cost-utility of the extension clinics were analyzed by using the Markov model. RESULTS: The total spending of extension clinics for 2008, 2009, and 2010 on average was ¥57 294, ¥80 752 and ¥74 739 respectively, or about ¥4379 annually per patient. The cost of averting one HIV infection was ¥316 509; the cost of averting one acquired immune deficiency syndrome (AIDS) patients was ¥508 676; and the cost of averting one death was ¥152 330. The cost of obtaining one life year (LY) was ¥3696 and the cost of obtaining one quality adjusted life year (QALY) was ¥9014. Comparing with drug users, the incremental cost utility ratio (ICUR) of the patients of the extension MMT clinics were -7074 yuan/QALY and -7162 yuan/LY. CONCLUSION: The extension MMT clinic service is lower in cost, and better in cost-effectiveness and cost-utility.

[Comprehensive evaluation of AIDS spending in Dehong prefecture of Yunnan province in 2010].

OBJECTIVE: To comprehensive evaluate the rationality of Acquired Immune Deficiency Syndrome (AIDS) expenditure through the analysis of AIDS expenditure circumstances based on the application of National AIDS Spending Assessment in Dehong prefecture in 2010. METHODS: Demographic and economic indicators of Mang City, Yingjiang, Longchuan, Ruili City, Lianghe and Wanting zone in Dehong prefecture of Yunnan province were collected from the reports issued by Dehong Statistical Bureau of 2010, and HIV/AIDS epidemic indicators were collected from the annual report of national AIDS prevention and control data.NASA method was used to analyze the actual spending and demand index was used to calculate the demand of AIDS funding in these counties (cities). The correlations between HIV/AIDS expenditures and demographic, economic and HIV/AIDS epidemic index were analyzed, respectively, as well as the correlation between the expenditures of AIDS prevention and control and proportion of major transmission approaches. RESULTS: In 2010, the actual expenditures on HIV/AIDS in the 5 counties (cities) of Dehong prefecture was ¥28 752 772, the population was 1 211 400, and Gross Domestic Product (GDP) was ¥11 693. The intervention expenditures in injection drug users, sexually transmitted people, and prevention of mother to child transmission in Ruili county were ¥130 345, ¥71 484 and ¥164 100, the proportions of HIV transmission in these groups were 23.9% (49/205), 73.7% (151/205), and 0.5% (1/205), respectively; and in Lianghe county was ¥141 665, ¥257 142, and ¥99 961, and the proportions of HIV transmission were 17.1% (6/35), 80.0% (28/35) and 0.0% (0/35), respectively. The intervention expenditures in Ruili and Lianghe counties were positive related to the proportion of corresponding people with HIV infection (both r values were 0.99, all P values < 0.05). In the other 4 counties (cities) and the development zone, no correlations. The expenditures of government departments, international projects, domestic research programs and personal and family pays (r value were 0.94, 0.83, 0.99 and 0.88, respectively, all P values < 0.05) were positive related to the number.Except the personal and family pays, other sources of expenditures were all positive related to the number of reported HIV/AIDS cases (r values were 0.94, 0.89 and 0.81, respectively, all P values < 0.05). CONCLUSION: Population and HIV/AIDS epidemic index were considered as factors in AIDS spending. The expenditures corresponded with the demand of different areas basically.

Anesthesia-related intervention for long-term survival and cancer recurrence following breast cancer surgery: A systematic review of prospective studies.

OBJECTIVE: Anesthesia is correlated with the prognosis of cancer surgery. However, evidence from prospective studies focusing on breast cancer is currently limited. This systematic review aimed to investigate the effect of anesthesia-related interventions on oncological outcomes following breast cancer surgery in prospective studies. METHODS: Literature searches were performed from inception to June. 2023 in the Pubmed, Web of Science, Embase, and ClinicalTrials databases. The main inclusion criteria comprised a minimum of one-year follow-up duration, with oncological outcomes as endpoints. Anesthesia-related interventions encompassed, but were not limited to, type of anesthesia, anesthetics, and analgesics. The risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 9 studies were included. Anesthesia-related interventions included paravertebral nerve block (3), pectoral nerve block (1), sevoflurane (2), ketorolac (2), and infiltration of lidocaine (1). Cancer recurrence, metastasis, disease-free survival, or (and) overall survival were assessed. Among all included studies, only infiltration of lidocaine was found to prolong disease-free survival and overall survival. CONCLUSION: Regional anesthesia and propofol did not improve oncological outcomes following breast cancer surgery. The anti-tumorigenic effect of ketorolac warrants future studies with larger sample sizes. Perioperative infiltration of lidocaine around the tumor may be a promising anti-tumorigenic intervention that can prolong overall survival in patients with early breast cancer.

Influence of extent of surgical resection on post-hepatectomy shoulder pain: an observational study.

Shoulder pain frequently follows hepatectomy. However, the influence of surgical procedures on shoulder pain is unclear. In this observational study, patients who underwent hepatectomy were enrolled in Shanghai Cancer Center. Shoulder pain and surgical pain were assessed using the numeric rating scale 2 days after surgery. The incidence of shoulder pain was the outcome of the cohort study. Nested case-control analyses were further applied. Three hundred and twelve patients were finally enrolled in this study. Nested case-control analysis showed that there were no significant differences in the number of surgical segments between the two groups (P = 0.09). In addition, minor hepatectomy did not reduce the incidence of shoulder pain compared with major hepatectomy (P = 0.37). The drainage volume within 2 days after surgery was significantly more in those patients with shoulder pain (P = 0.017). In open surgery, surgical sites involving the right anterior lobe (OR (95% CI) 2.021 (1.075, 3.802), P = 0.029) and right posterior lobe (OR (95% CI) 2.322 (1.193, 4.522), P = 0.013) were both independent risk factors for shoulder pain. Left shoulder pain also occurred in patients who did not receive left lateral hepatectomy. The preventive phrenic nerve block was not suitable for post-hepatectomy shoulder pain. Stronger preventative intervention should be used in those high-risk patients.

Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China.

Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.

Immediate and long-term outcomes after treat-all among people living with HIV in China: an interrupted time series analysis.

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.

[The application of National AIDS spending assessment in a county of Dehong prefecture, Yunnan province, China].

OBJECTIVE: To calculate the actual expenditures in a county of Dehong prefecture, Yunnan province, China by using the method of National AIDS Spending Assessment (NASA) in 2010. METHODS: Data were collected through NASA data collection form based on adapted NASA classification in the county of Dehong prefecture from October to December, 2011, and complemented by semi-structured interview with 16 well trained programmatic and financial representatives in 8 spending units. Data were entered in Resource Tracking Software (RTS) V 2009.3.0, and SPSS 13.0 was used for data processing and analysis. RESULTS: The NASA estimations showed that the county spent a total of ¥16 235 954 on HIV/AIDS in 2010. Public funds constituted 96.3% of the total expenditure (¥15 630 937), followed by Global Fund which accounted for 3.0% (¥484 585) and private sources which accounted for 0.7% (¥120 432). Findings based on NASA categories showed that AIDS spendings were mainly on 4 areas, and expenditure on Care & Treatment was ¥12 401 382 (76.4% of total expenditure), followed by Prevention which accounted for 14.3% (¥2 325 707), Program Management & Administration which accounted for 7.8% (¥1 268 523) and human resources which accounted for 1.5% (¥240 342). The most beneficial population group was People Living with HIV (PLHIV), accounting for 84.7% of total expenditure. (¥13 753 428), followed by 4.8% for high risk population, including female sex workers and their partners (¥297 333), injection drug users and their partners (¥293 143), men having sex with men and their partners (¥185 136) and 1.5% (¥241 429) for the general population. CONCLUSION: The local funds for HIV/AIDS in this county was insufficient. The local government should increase corresponding funds based on central government funding. Care and treatment was the first spending priority in the county and the investment of prevention services needs to be increased. Prevention and treatment and care should be combined to ensure the effectiveness of comprehensive prevention and treatment of AIDS.

Untargeted Plasma Metabolomics Reveals Extensive Metabolic Alterations Among Treatment-Naive Human Immunodeficiency Virus/Hepatitis C Virus Co-Infected Patients with Liver Disease Progression.

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may induce metabolic disorders and cause liver complications. Therefore, we aim to analyze the metabolite differences among treatment-naive HIV/HCV co-infected patients with versus without liver disease progression (LDP) and HIV mono-infected patients. A cross-sectional study was conducted in 65 HIV/HCV co-infected patients (22 with LDP and 43 without) and 65 HIV mono-infected patients in Dehong prefecture of Yunnan province, China. Plasma metabolomics were measured by gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Discrimination analysis, pathway enrichment analysis, generalized linear model with binomial distribution, and area under the receiver-operating characteristic curve (AUC) were conducted to identify bilateral differences in metabolites and pathways in different comparison groups. A total of 10,831 with 673 named and 10,158 unnamed metabolites were detected. Compared with HIV/HCV co-infected patients without LDP, phenylalanine, tyrosine, and tryptophan biosynthesis pathway with the increased level of tyrosine were significantly altered among HIV/HCV co-infected patients with LDP. Compared with HIV mono-infected patients, the decreased level of glutamine and increased levels of glutamic acid, arachidonic acid, and its derivatives were identified among HIV/HCV co-infected patients. Metabolite panels adjusted for baseline information had a higher accuracy than baseline model (without metabolite information) in distinguishing HIV/HCV co-infected patients with versus without LDP (AUC 0.951 vs. 0.849, p = .027) and HIV/HCV co-infected patients from HIV mono-infected patients (AUC 0.889 vs. 0.766, p < .001). A novel set of metabolites were found to discriminate HIV/HCV co-infected patients with versus without LDP, and from HIV mono-infected patients, which may have mechanistic and interventional implications.

Longitudinal impact of compliance with routine CD4 monitoring on all cause deaths among treated people with HIV in China.

Keeping adherence to the continuous and standardized CD4 follow-up monitoring service is of great significance to the control of disease progression and the reduction of avoidable mortality for HIV-infected patients. As non-communicable diseases (NCDs) have become main causes of deaths for people with HIV (PWH) in the era of combination antiretroviral therapy (cART), how and to what extent does adherence to routine CD4 monitoring differentially impact on AIDS-related versus NCDs-related deaths in low- and middle-income countries (LMIC) remains elucidated. A CD4 test index was developed by dividing the actual number of received CD4 tests by the theoretical number of CD4 tests that should have been performed according to national treatment guidelines during the study period, with an index value of 0.8-1.2 reflecting compliance. From 1989 to 2020, 14,571 adults were diagnosed with HIV infection in Dehong Prefecture of Yunnan province in Southwestern China, 6,683 (45.9%) PWH had died with the all-cause mortality of 550.13 per 10,000 person-years, including 3,250 (48.6%) AIDS-related deaths (267.53 per 10,000 person-years). Among patients on cART, the median CD4 test index was 1.0 (IQR 0.6-1.3), and 35.2% had a CD4 test index less than 0.8. Cox proportional hazards regression analysis indicated that PWH with CD4 test index at 0.8-1.2 were at the lowest risk of both AIDS-related (aHR = 0.06; 95%CI: 0.05-0.07) and NCDs-related (aHR = 0.13; 95%CI: 0.11-0.16)deaths. Adherence to routine CD4 monitoring is critical for reducing both AIDS-related and NCDs-related mortality of PWH. An appropriate (once or twice a year) rather than an unnecessarily higher frequency of routine CD4 testing could be most cost-effective in reducing mortality in LMIC.

The impact of COVID-19 non-pharmaceutical interventions on HIV care continuum in China: An interrupted time series analysis.

Background: China implemented strict non-pharmaceutical interventions to contain COVID-19 at the early stage. We aimed to evaluate the impact of COVID-19 on HIV care continuum in China. Methods: Aggregated data on HIV care continuum between 1 January 2017 and 31 December 2020 were collected from centers for disease control and prevention at different levels and major infectious disease hospitals in various regions in China. We used interrupted time series analysis to characterize temporal trend in weekly numbers of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, HIV diagnoses, median time intervals between HIV diagnosis and antiretroviral therapy (ART) initiation (time intervals, days), ART initiations, mean CD4+ T cell counts at ART initiation (CD4 counts, cells/µL), ART collections, and missed visits for ART collection, before and after the implementation of massive NPIs (23 January to 7 April 2020). We used Poisson segmented regression models to estimate the immediate and long-term impact of NPIs on these outcomes. Findings: A total of 16,780 PEP prescriptions, 1,101,686 HIV tests, 69,659 HIV diagnoses, 63,409 time intervals and ART initiations, 61,518 CD4 counts, 1,528,802 ART collections, and 6656 missed visits were recorded during the study period. The majority of outcomes occurred in males (55·3-87·4%), 21-50 year olds (51·7-90·5%), Southwestern China (38·2-82·0%) and heterosexual transmission (47·9-66·1%). NPIs was associated with 71·5% decrease in PEP prescriptions (IRR 0·285; 95% CI 0·192-0·423), 36·1% decrease in HIV tests (0·639, 0·497-0·822), 32·0% decrease in HIV diagnoses (0·680, 0·511-0·904), 59·3% increase in time intervals (1·593, 1·270-1·997) and 17·4% decrease in CD4 counts (0·826, 0·746-0·915) in the first week during NPIs. There was no marked change in the number of ART initiations, ART collections and missed visits during the NPIs. By the end of 2020, the number of HIV tests, HIV diagnoses, time intervals, ART initiations, and CD4 counts reached expected levels, but the number of PEP prescriptions (0·523, 0·394-0·696), ART collections (0·720, 0·595-0·872), and missed visits (0·137, 0·086-0·220) were still below expected levels. With the ease of restrictions, PEP prescriptions (slope change 1·024/week, 1·012-1·037), HIV tests (1·016/week, 1·008-1·026), and CD4 counts (1·005/week, 1·001-1·009) showed a significant increasing trend. Interpretation: HIV care continuum in China was affected by the COVID-19 NPIs at various levels. Preparedness and efforts to maintain the HIV care continuum during public health emergencies should leverage collaborations between stakeholders. Funding: Natural Science Foundation of China.