[Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021].

Objective: To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021. Methods: The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis. Results: A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M (Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m2 and baseline CD4+T lymphocyte (CD4) counts <200 cells/µl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m2 and baseline CD4 counts ≥200 cells/µl were more likely to have complete immune reconstitution. Conclusions: In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

Evaluation of factors associated with high advanced HIV disease and mortality in Southwestern China: a retrospective cohort study, 2005-2020.

OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.

[Analysis of late-diagnosis and associated factors in newly reported HIV infections among men who have sex with men in Guangxi Zhuang Autonomous Region, 2005-2021].

Objective: To analyze the trend of late-diagnosis of HIV-infected men who have sex with men (MSM) before and after the AIDS Conquering Project in Guangxi Zhuang Autonomous Region (Guangxi) and its influencing factors, in order to find out the population groups that need priority intervention at the present stage. Methods: The HIV-infected MSM in Guangxi from 2005-2021 were selected from the National Integrated HIV/AIDS Control and Prevention Data System. The Joinpoint 4.9.1.0 software was used to test the time trend of late-diagnosis and non-late-diagnosis cases, and logistic regression was applied to analyze the factors influencing the proportion of late-diagnosis at each stage. Results: From 2005 to 2021, 5 764 HIV-infected MSM were reported in Guangxi from 2005 to 2021, with an overall late-diagnosis of 28.45% (1 640 cases). Under the 2015 baseline data as the boundary, the proportion of late-diagnosis cases showed a trend of sharp decline followed by stabilization from 2005 to 2015, average annual percent change= -6.90% (P<0.001). The effect of factors such as resident population, occupation as a farmer or worker, and sample originating from medical consultation on late-diagnosis changed considerably before and after the implementation of the project, and the factors influencing late-diagnosis at this stage were age, resident population, occupation as a farmer, worker or student. The factors influencing late-diagnosis at this stage are age, resident population, and occupation as a farmer, worker and a student. Conclusions: The proportion of late diagnosis cases of HIV-infected MSM in Guangxi decreased significantly before and after the project. However, late-diagnosis should not be neglected and precise prevention and control should be carried out for the resident population, farmers, workers or students.

[Analysis of HIV transmission hotspots and characteristics of cross-regional transmission in Guangxi Zhuang Autonomous Region based on molecular network].

Objective: To analyze HIV transmission hotspots and characteristics of cross-regional transmission in Guangxi Zhuang autonomous region (Guangxi) based on the molecular network analysis, and provide evidence for optimization of precise AIDS prevention and control strategies. Methods: A total of 5 996 HIV pol sequences sampled from Guangxi between 1997 and 2020 were analyzed together with 165 534 published HIV pol sequences sampled from other regions. HIV-TRACE was used to construct molecular network in a pairwise genetic distance threshold of 0.5%. Results: The proportion of HIV sequences entering the molecular network of HIV transmission hotspots in Guangxi was 31.5% (1 886/5 996). In the molecular network of HIV cross-regional transmission, the links within Guangxi accounted for 51.6% (2 613/5 062), the links between Guangxi and other provinces in China accounted for 48.0% (2 430/5 062), and the links between Guangxi and other countries accounted for 0.4% (19/5 062). The main regions which had cross-regional linked with Guangxi were Guangdong (49.5%, 1 212/2 449), Beijing (17.5%, 430/2 449), Shanghai (6.9%, 168/2 449), Sichuan (5.7%, 140/2 449), Yunnan (4.2%, 102/2 449), Shaanxi (3.8%, 93/2 449), Zhejiang (2.8%, 69/2 449), Hainan (2.0%, 49/2 449), Anhui (1.5%, 37/2 449), Jiangsu (1.3%, 33/2 449), and other regions (each one <1.0%), respectively. The risk factors of entering the molecular network of HIV transmission hotspots in Guangxi included being aged ≥50 years (compared with being aged 25-49 years, aOR=1.68,95%CI:1.46-1.95), males (compared with females, aOR=1.21,95%CI:1.05-1.40), being single (compared with being married, aOR=1.18,95%CI:1.00-1.39), having education level of high school or above (compared with having education level of junior high school or below, aOR=1.21,95%CI:1.04-1.42), acquired HIV through homosexual intercourse (compared with acquired with HIV through heterosexual intercourse, aOR=1.77, 95%CI:1.48-2.12). The risk factors of cross-regional transmission included males (compared with females, aOR=1.74,95%CI:1.13-2.75), having education level of high school or above (compared with having education level of junior high school or below, aOR=1.96,95%CI:1.43-2.69), being freelancer/unemployed/retired (compared with being farmers, aOR=1.50,95%CI:1.07-2.11), acquired HIV through homosexual intercourse (compared with acquired with HIV through heterosexual intercourse, aOR=3.28,95%CI:2.30-4.72). Conclusion: There are HIV transmission hotspots in Guangxi. Guangxi and other provinces in China form a complex cross-regional transmission network. Future studies should carry out social network surveys in high-risk populations inferred from the molecular network analysis for the timely identification of hidden transmission chains and reduction of the second-generation transmission of HIV.

[Immunization effect and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell levels].

Objective: To explore the immunogenicity and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell (CD4) levels, and analyze the influence effect of CD4 levels on immunization response. Methods: A total of 182 HIV-infected patients who participated in a randomized controlled trial of 20 µg and 60 µg hepatitis B vaccination at month 0, 1, and 6 in 2014 by Guangxi Zhuang Atonomous Region CDC and Ningming county CDC were surveyed. Six months later after the first dose and 1 month, 6 months, 1 year, and 3 years later after the full course of the vaccination, 5 ml of the venous blood of the patients was collected, and the anti-HBs was detected by Chemiluminescent Microparticle Immunoassay (CMIA). On the basis of previous studies, this study focused on analyzing the immunogenicity and persistence of hepatitis B vaccine under different CD4 levels. Results: One month later after the whole course of hepatitis B vaccination, the anti-HBs geometric mean concentration (GMC), anti-HBs positive rate (≥10 mIU/ml) and strong positive rate (≥100 mIU/ml) in HIV patients with CD4 <350 cells/µl were 442.50 mIU/ml, 71.05% (27/38) and 44.74% (17/38), respectively, which were significantly lower than those HIV-infected patients with CD4 ≥350 cells/µl [583.90 mIU/ml, 92.13% (117/127) and 77.95% (99/127)] (P<0.05). After controlling the confounding factors, the probability of being anti-HBs positive induced by hepatitis B vaccine in patients with CD4 <350 cells/µl was 0.14 times higher than in those with CD4≥350 cells/µl (95%CI: 0.03-0.62), and patients with CD4 <350 cells/µl had higher risk of no response. From 6 months to 3 years after the whole course of the vaccination, the anti-HBs GMC (195.00-27.55 mIU/ml vs. 300.10-45.81 mIU/ml), the positive rate (56.67%-36.67% vs. 78.57%- 51.58%) and the strong positive rate (33.33%-6.67% vs.44.64%-15.79%) in patients with CD4 <350 cells/µl gradually declined, lower than the levels in those with CD4 ≥350 cells/µl. Conclusions: HIV-infected patients with CD4 <350 cells/µl have high risk of no response to hepatitis B vaccination and poor immune persistence. It is necessary to strengthen the anti-HBs monitoring in HIV-infected patients, with special attention to those with CD4 <350 cells/µl. When anti-HBs is negative, hepatitis B vaccine should be injected as early as possible.

[Non-occupational post-exposure prophylaxis in men who have sex with men in Guangxi Zhuang Autonomous Region].

Objective: To analyze the effects of HIV non-occupational post-exposure prophylaxis (nPEP) in men who have sex with men (MSM) in Nanning and Liuzhou, Guangxi Zhuang Autonomous Region. Methods: Participants were recruited through community publicity and advocacy under a "Trinity" approach among non-governmental organizations (NGO), CDCs/hospitals and pharmacies. Basic information, drug taking and follow-up tests of participants who had enrolled for 28 days of the research were collected. Descriptive statistics were used for data analysis. Results: From September 2017 to March 2019, a total of 213 MSM cases consulted for nPEP service, 159 of them were eligible for nPEP, and 154 were enrolled in the study for drug taking. For 132 cases enrolled in the study for 28 days and above, 118 completed the 28-day course of antiretroviral therapy (ART), while 10 failed to complete the 28-day course of ART, and 4 could not be confirmed whether completed the full course of ART due to loss of contact. For those who completed 28-day course of ART, 94.1% (111/118) and 75.4% (89/118) respectively received HIV tests at 4-6 weeks and 3 months after exposure, the results were all HIV negative. Conclusion: Under the "Trinity" approach, taking antiviral drugs earlier after HIV non-occupational exposure can effectively reduce the risk of HIV infection and to some extent, reduce the new infection cases.

[Influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV].

Objective: To explore influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV (PMTCT) in Guangxi Zhuang autonomous region, and provide evidence for the improvement PMTCT program. Methods: This retrospective case control study was conducted in 554 HIV negative infants aged 18 months whose HIV positive mothers had received PMTCT services reported through PMTCT system database from January 1, 2010 to December 31, 2017 and 1 109 healthy infants born in 2017, whose mothers were healthy, in Lingshan, Luzhai, and Hengxian counties, ranking top three counties with high HIV infection prevalence, in Guangxi. PMTCT data and physical development data such as height, weight and head circumference of children aged 18 months were collected. The physical dysplasia in the infants was defined as at least one of the three main indicators of height, weight and head circumference below the normal range. Results: The number of HIV-positive mother and their infants in the case group were 667 and 554 respectively, and the PMTCT rates were 91.15% (608/667) and 96.57% (535/554) respectively. HIV positive rate, mortality rate and mother to child transmission rate of the infants aged 18 months were 1.44% (8/554), 3.07% (17/554) and 1.91% (8/418) respectively, and the physical examination results of the infants aged 18 months showed that the physical dysplasia rate was 30.51% (169/554). Among the 1 109 infants in the control group, the physical dysplasia rate was 9.83% (109/1 109). The difference between the case group and the control group was significant (P<0.01). Conclusion: The PMTCT rates of HIV positive mother and their children were more than 90.00%, respectively. However, poor physical development rate of infants aged 18 months were more than 30.00%. The possible influence of PMTCT on physical development of the infants aged 18 months of HIV positive mother's needs to be further studied.

[HIV genetic subtypes and comparison of the first CD(4)(+)T cell counts in newly diagnosed HIV infected patients in Liuzhou, 1998-2012].

Objective: To analyze the change trend of HIV genetic subtypes and compare the first CD(4)(+)T cell counts of newly diagnosed HIV infected patients in Liuzhou from 1998 to 2012, and provide a reference for AIDS prevention and control. Methods: Newly diagnosed HIV-infected patients from 1998 to 2012 in Liuzhou were selected through national HIV/ADIS comprehensive response information management system. Their plasma samples were used for RNA gene extraction, amplification, sequencing and genotyping. Coharan-Armitage trend test was used to analyze the ratio trend of genetic subtypes and phylogenetic clusters of HIV and Wilcoxon Rank Sum Test was used to compare the first CD(4)(+)T cell counts (CD(4)) of the different subtype HIV infected patients. Results: A total of 1 877 newly diagnosed HIV infected patients were included in the study. From 1998 to 2012, the proportions of CRF01_AE and CRF01_AE (Cluster 1) increased from 78.4% (76/97) to 91.5% (1 441/1 574), from 63.9% (62/97) to 74.0% (1 164/1 574), and the proportion of CRF07_BC decreased from 17.5% (17/97) to 4.6% (72/1 574), respectively (Z=4.632, P<0.001; Z=2.455, P=0.014; Z=-5.943, P<0.001). The median and interquartile range of the first CD(4) of the patients infected with subtype CRF01_AE (Cluster 1), CRF01_AE (Cluster 2), CRF07_BC and CRF08_BC were 230 (83-375), 215 (48-351), 365 (254-503) and 334 (206-479) cell/µl, respectively. The first CD(4) levels of the patients infected with subtype CRF01_AE (Cluster 1) or CRF01_AE (Cluster 2) were significantly lower than those of CRF07_BC (Z=-4.795, P<0.001; Z=-4.238, P<0.001). Conclusion: The genetic subtypes of HIV were mainly CRF01_AE in newly diagnosed HIV-infected patients and this subtype proportion was in increase and the first CD(4) levels of the patients were low in Liuzhou during 1998 to 2012.

[Epidemiological characteristics of HIV/AIDS in Guangxi Zhuang Autonomous Region, 2010-2017].

Objective: To understand the characteristics of HIV/AIDS epidemic in Guangxi Zhuang Autonomous Region (Guangxi) with a purpose to accurately provide scientific basis for prevention and control measures, 2010-2017. Methods: Data were retrieved from case reporting cards of Guangxi during 2010 to 2017 through National HIV/AIDS Comprehensive Response Information Management System. Data was analyzed using epidemiological methods such number of cases, proportion and rate. χ(2) test was used for statistical analysis. Results: The HIV positive rate was 12.53 per ten thousand (85 182/67 959 000) in Guangxi during 2010 to 2017. The number of newly diagnosed HIV/AIDS cases and the number of death yearly respectively increased by 22.34%(2 602/11 648) and 32.83% (952/2 900) in 2011 compared with 2010, and both showed a six-year continuous downward trend (the number of newly diagnosed cases respectively 12 229 cases, 10 877 cases, 9 460 cases, 9 190 cases, 8 848 cases, 8 680 cases, and the number of death respectively 3 888 cases, 3 316 cases, 2 914 cases, 2 717 cases, 2 595 cases, 2 600 cases) from 2012 to 2017. But proportion of late discovery remained above 50.00% (50.53%-57.06%) for eight-years continuously. The ratio of male and female was 2.47 ∶ 1 (60 639/24 543). The ratio of males and females aged 50 and over was 2.71∶1 (28 654/10 557). Proportion of the cases in 25-49 years old group and 50 years old group accounting for 47.40%(40 377/85 182) and 46.03% (39 211/85 182) respectively. The occupation was farmers accounting for 68.40% (58 262/85 182), housekeeping, housework and unemployment accounting for 11.21% (9 546/85 182), student accounting for 0.86% (729/85 182). Heterosexual transmission accounted for 90.60% (77 171/85 182, homosexual transmission accounted for 3.13% (2 669/85 182), injection drug use transmission accounted for 4.60%(3 924/85 182) and mother-to-child transmission accounted for 0.73% (619/85 182). Conclusions: The number of newly diagnosed cases and the number of death yearly showed a continuous downtrend for six-years from 2012 to 2017. However, proportion of late discovery remained above 50.00% for eight-years. The major route of infection was heterosexual transmission. With the change of HIV/AIDS newly epidemic mode in Guangxi, there are many new challenges for HIV/AIDS prevention and control work. Strategy of targeted intervention modes should be innovated for a new breakthrough.

[Characteristics of HIV-infected persons without long term disease progress and related factors in Guangxi Zhuang Autonomous Region].

Objective: To understand the characteristics of HIV infected persons without long term disease progress [also known as long term non-progressors (LTNPs)], and related factors in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data of persons living with HIV and receiving no antiretroviral therapy in Guangxi by the end of 2016 were collected from the national HIV/AIDS comprehensive control and prevention information system of China. Results: By the end of 2016, there were 313 LTNPs in Guangxi, accounting for 2.3% of those being reported for more than 10 years, 5.4% of those being reported for more than 10 years and surviving, and 26.6% of those being reported for more than 10 years, surviving and receiving no antiretroviral therapy. Among the LTNPs, 87.2%(273) were men, 94.9% (297) were aged ≤ 40 years, 32.3% (101) were farmers, 55.6% (174) were single, divorced or widowed, 69.3% (217) were of Han ethnic group, 68.1% (213) were injecting drug users, and 52.1% (163) were from custody facilities. Multiple logistic regression analysis indicated that factors associated with delayed disease progression included age ≤40 years (compared with age >40 years, aOR=1.55, 95%CI: 1.31-3.12) and injection drug use (compared with sexual transmission, aOR=1.23, 95%CI: 1.10-1.74). Conclusions: A number of LTNPs existed in HIV-infected individuals in Guangxi. Further research are needed to identify the related factors, and it is necessary to conduct large sample size studies on host immunology, genetics and the virology of HIV to explore the related mechanism.

[Study on HIV-1 subtype among elderly male clients and female sex workers of low-cost venues in Guangxi Zhuang Autonomous Region, China].

Objective: To understand HIV-1 subtype characteristics and transmission clusters in elderly male clients and female sex workers (FSWs) of low-cost commercial sex venues in Guangxi Zhuang Autonomous Region, China. Methods: A cross sectional survey was conducted in FSWs and elderly male clients (≥50 years) of low-cost commercial sex venues in 4 cities and 9 counties in Guangxi Zhuang Autonomous Region by convenient sampling in 2012. The blood sample was collected from each case for HIV-1 antibody detection. The pol gene fragments were amplified and sequenced from viral RNA template extracted from plasma samples. The phylogenetic tree was constructed and the subtypes were identified. Results: A total of 4 048 elderly male clients and 784 FSWs were surveyed, and 116 HIV-1 infections were detected, the positive rate was 2.5% (103/4 048) in the clients and 1.7% (13/784) in FSWs. The gene amplification and sequencing of HIV-1 detected in 84 blood samples indicated that 53 pol gene sequences were successfully determined (48 blood samples from elderly male clients and 5 blood samples from FSWs). Among 53 pol sequences, 48(90.6% ), 4(7.5% ), and 1(1.9% ) sequences were identified as CRF01_AE, CRF08_BC, and CRF07_BC, respectively. Two transmission clusters were identified among CRF01_AE, including 4 sub-clusters. One transmission cluster was identified among CRF08_BC. The transmission cluster or sub-cluster were from the infected individuals at same low-cost commercial sex venue, or different low-cost commercial sex venues in the same town, or same place, or adjacent villages and towns. Conclusions: CRF01_AE was the predominant HIV-1 subtype among elderly male clients and FSWs of low-cost commercial sex venues in Guangxi Zhuang Autonomous Region, circulating in same venue or adjacent villages and towns. The HIV-1 positive male clients and FSWs might play an important role in the spread of the strains.

[Prevalence and related factors of HIV/HBV coinfection among HIV/AIDS patients].

Objective: To reveal the prevalence and the related factors of hepatitis B (HepB) virus infection among HIV/AIDS patients. Methods: We conducted a cross-sectional study in two HIV clinics, affiliated to local Centers of Disease Control and Prevention in Guangxi Zhuang Autonomous Regional. A face-to-face interview, with questionnaire was conducted to collect information on socio-demographic characteristics, drug use, and sexual behavior. Blood samples were used to test HBsAg. χ(2) test or Fisher's exact test and unconditional logistic regression models were used to identify the influencing factors. Results: The prevalence of HBV and HIV co-infection was 13.85% (113/816). Results from multivariate logistic regression analyses showed that age (25-45), family history of HBV and history of HepB vaccination were independent influencing factors for HBV and HIV coinfection, with OR (95%CI) as 1.738 (1.031-2.931), 2.898 (1.678-5.005) and 1.744 (1.052-2.892), respectively. Conclusion: The prevalence of HBV among HIV/AIDS patients was significantly higher than that in general population. HIV/AIDS patients aged between 25 and 45 and with family history of HBV were more likely to be infected with HBV, while HepB vaccination was associated with the reduction of HIV/HBV coinfection. Specific comprehensive prevention and treatment programs on HIV/AIDS patients need to be set up.

Resistance and resilience of nitrifying bacteria in aerobic granules to pH shock.

UNLABELLED: To investigate the response difference between flocculent sludge and granular sludge in unfavourable environmental conditions, 1-h pH shock was exerted to both granular sludge and flocculent sludge with the same biomass concentration and the same population sizes of nitrifying bacteria. It was found that nitrite-oxidizing bacteria (NOB) were more sensitive to pH than ammonia-oxidizing bacteria (AOB). In addition, the deviation of 3 pH units to alkaline from the optimal pH was much more detrimental to AOB and NOB in both flocculent sludge and granular sludge compared with the deviation of 3 pH units to acidic. However, respirometric activities of both AOB and NOB in granular sludge after pH shock at 5 and 11 were much higher than those in the flocculent sludge. The recovery of nitrifying activities by only one batch culture indicated that nitrifying bacteria in granular sludge experienced a much less irreversible loss compared with flocculent sludge. The results in this study showed that compact structure and the big size of granules could play a buffering role to unfavourable conditions which resulted in a much higher resistance and resilience to shock. SIGNIFICANCE AND IMPACT OF THE STUDY: This study aims to provide some guidance to the application of aerobic granular sludge to real wastewater which might experience fluctuated pH. The findings in this study indicate that resistance and resilience of nitrifying bacteria in mature granules to pH shock at steady state is much better than flocculent sludge, suggesting more robust and flexible operation of granular sludge compared with traditional flocculent sludge. In addition, the results in this study underlined a more serious inhibition from free ammonia at high pH than free nitrous acid at low pH as well as the inaccuracy of reported bell-shaped modelling of pH effect on nitrification.