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ObjectivesThere is still no study focused on willingness to pay for long-acting injectable cabotegravir (CAB-LA) after it was available on the market in the United States in 2021. Here, we explored the willingness to pay for CAB-LA and associated factors and price elasticity of demand (PED) of CAB-LA among men who have sex with men (MSM) in Guangxi, China.MethodsA cross-sectional study was conducted. Univariate and multivariate ordinal logistic regression analyses were performed to explore the associated factors of willingness to pay for CAB-LA. PED was used to measure the change in the number of participants willing to pay to a change in price.ResultsA total of 1,006 MSM were recruited, among which 84.1% were aged between 18 and 39 years old. The median (interquartile) of the maximum amount of willing to pay for CAB-LA was 200 (100–500) Chinese yuan (CNY) per month. Most (84.2%) were willing to pay less than 600 CNY per month. The number of participants willing to pay for CAB-LA significantly increased with decrease in the price. When the price (CNY per month) decreased from 600 to 500, 500 to 400, 400 to 300, and 300 to 200, PED was 3.13, 1.64, 1.33, and 1.17, respectively. The maximum amount of willing to pay for CAB-LA was positively associated with younger age (vs. ≥40 years group, 18–24 years group, aOR: 1.94, 95% CI: 1.32–2.85; 25–39 year group, aOR: 1.70, 95% CI: 1.20–2.42), being high educated (vs. middle school or lower group, high school or college group, aOR: 1.61, 95% CI: 1.06–2.48; bachelor’s degree or above group, aOR: 2.21, 95% CI: 1.41–3.49), monthly income ≥6000 CNY (vs.

Abstract BackgroundIn recent years, the number of HIV/AIDS cases among youth has increased year by year around the world. A spatial and temporal analysis of these AIDS cases is necessary for the development of youth AIDS prevention and control policies. ObjectiveThis study aimed to analyze the spatial and temporal distribution and associated factors of HIV/AIDS among youth in Guangxi as an example. MethodsThe reported HIV/AIDS cases of youths aged 15‐24 years in Guangxi from January 2014 to December 2021 were extracted from the Chinese Comprehensive Response Information Management System of HIV/AIDS. Data on population, economy, and health resources were obtained from the Guangxi Statistical Yearbook. The ArcGIS (version 10.8; ESRI Inc) software was used to describe the spatial distribution of AIDS incidence among youths in Guangxi. A Bayesian spatiotemporal model was used to analyze the distribution and associated factors of HIV/AIDS, such as gross domestic product per capita, population density, number of health technicians, and road mileage per unit area. ResultsFrom 2014 to 2021, a total of 4638 cases of HIV/AIDS infection among youths were reported in Guangxi. The reported incidence of HIV/AIDS cases among youths in Guangxi increased from 9.13/100,000 in 2014 to 11.15/100,000 in 2019 and then plummeted to a low of 8.37/100,000 in 2020, followed by a small increase to 9.66/100,000 in 2021. The districts (counties) with relatively high HIV/AIDS prevalence among youths were Xixiangtang, Xingning, Qingxiu, Chengzhong, and Diecai. The reported incidence of HIV/AIDS among youths was negatively significantly associated with road mileage per unit area (km) at a posterior mean of −0.510 (95% CI −0.818 to 0.209). It was positively associated with population density (100 persons) at a posterior mean of 0.025 (95% CI 0.012‐0.038), with the number of health technicians (100 persons) having a posterior mean of 0.007 (95% CI 0.004‐0.009). ConclusionsIn Guangxi, current HIV and AIDS prevention and control among young people should focus on areas with a high risk of disease. It is suggested to strengthen the allocation of AIDS health resources and balance urban development and AIDS prevention. In addition, AIDS awareness, detection, and intervention among Guangxi youths need to be strengthened.

Abstract Objectives To evaluate the prevention efficacy of scaling up HIV/AIDS antiretroviral therapy (ART) on HIV transmission at the population level and determine associated factors of HIV secondary transmission. Methods We used HIV longitudinal molecular networks to assess the genetic linkage between baseline and newly diagnosed cases. A generalized estimating equation was applied to determine the associations between demographic, clinical characteristics and HIV transmission. Results Patients on ART had a 32% lower risk of HIV transmission than those not on ART. A 36% reduction in risk was also seen if ART-patients maintained their HIV viral load lower than 50 copies/mL. A 71% lower risk occurred when patients sustained ART for at least 3 years and kept HIV viral load less than 50 copies/mL. Patients who discontinued ART had a similar HIV transmission risk as those not on ART. Patients who were older, male, non-Han, not single, retired, infected via a heterosexual route of transmission and those who possessed higher CD4 counts had a higher risk of HIV transmission. HIV-1 subtype of CRF01_AE was less transmissible than other subtypes. Conclusions The efficacy of ART in a real-world setting was supported by this longitudinal molecular network study. Promoting adherence to ART is crucial to reduce HIV transmission.

ABSTRACT CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4+ T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types. Their mechanisms of pathogenicity were evaluated by co-receptor tropisms, predicted by genotyping and confirmed with virus isolate phenotyping, as well as inflammation parameters. Our research elucidated that individuals infected with CRF01_AE clusters 1 and 2 exhibited significantly lower baseline CD4+ T-cell counts and greater CD4+ T-cell loss in cohort follow-up, compared with other HIV-1 sub-types and CRF01_AE clusters. The increased pathogenesis of cluster 1 or 2 was associated with higher CXCR4 tropisms, higher inflammation/immune activation, and increased pyroptosis. The protein structure modeling analysis revealed that the envelope V3 loop of clusters 1 and 2 viruses is favorable for CXCR4 co-receptor usage. Imbedded with the most mutating reverse transcriptase, HIV-1 is one of the most variable viruses. CRF01_AE clusters 1 and 2 have been found to have evolved into more virulent strains in regions with predominant heterosexual infections. The virulent strains increased the pressure for early diagnosis and treatment in HIV patients. To save more lives, HIV-1 surveillance systems should be upgraded from serology and genotyping to phenotyping, which could support precision interventions for those infected by virulent viruses.IMPORTANCERetroviruses swiftly adapt, employing error-prone enzymes for genetic and phenotypic evolution, optimizing survival strategies, and enhancing virulence levels. HIV-1 CRF01_AE has persistently undergone adaptive selection, and cluster 1 and 2 infections display lower counts and fast loss of CD4+ T cells than other HIV-1 sub-types and CRF01_AE clusters. Its mechanisms are associated with increased CXCR4 tropism due to an envelope structure change favoring a tropism shift from CCR5 to CXCR4, thereby shaping viral phenotype features and impacting pathogenicity. This underscores the significance of consistently monitoring HIV-1 genetic evolution and phenotypic transfer to see whether selection bias across risk groups alters the delicate balance of transmissible versus toxic trade-offs, since virulent strains such as CRF01_AE clusters 1 and 2 could seriously compromise the efficacy of antiviral treatment. Only through such early warning and diagnostic services can precise antiviral treatments be administered to those infected with more virulent HIV-1 strains.

Abstract Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of “COVID-19 epidemic”, “Novel Coronavirus” and “COVID-19” can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0–28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5–8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1–3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70–0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase.

Objectives To evaluate the diagnostic performance of urine HIV antibody rapid test kits in screening diverse populations and to analyse subjects’ willingness regarding reagent types, purchase channels, acceptable prices, and self-testing.Designs Diagnostic accuracy studiesParticipants A total of 2606 valid and eligible samples were collected in the study, including 202 samples from female sex workers (FSWs), 304 persons with injection drug use (IDU), 1000 pregnant women (PW), 100 subjects undergoing voluntary HIV counselling and testing (VCT) and 1000 students in higher education schools or colleges (STUs). Subjects should simultaneously meet the following inclusion criteria: (1) being at least 18 years old and in full civil capacity, (2) signing an informed consent form and (3) providing truthful identifying information to ensure that the subjects and their samples are unique.Results The sensitivity, specificity and area under the curve (AUC) of the urine HIV-1 antibody rapid test kits were 92.16%, 99.92% and 0.960 (95% CI: 0.952 to 0.968, p

Abstract Background Previous studies have not clearly demonstrated the impact of behavioral and emotional problems (BEDs) on treatment outcomes among HIV-infected children on antiretroviral therapy (ART). This study aimed to describe the prevalence of BEDs among this population and identify the factors associated with HIV treatment outcomes. Methods This cross-sectional study was conducted in Guangxi, China, between July and August 2021. HIV-infected children answered questionnaires about BEDs, physical health, social support, and whether they have missed doses in the past month. BEDs were assessed using the Chinese version of the self-reported Strengths and Difficulties Questionnaire (SDQ-C). The self-reported survey data were linked to participants’ HIV care information that was obtained from the national surveillance database. Univariate and multivariate logistic regression models were used to identify factors that were associated with missed doses in the past month and virological failure. Results The study sample was 325 HIV-infected children. HIV-infected children had a higher proportion of abnormal scores on SDQ-C total difficulties compared to their peers in the general population (16.9 vs 10.0%; P = 0.002). An abnormal SDQ-C total difficulties score (AOR = 2.06, 95%CI: 1.10–3.88) and infrequency of receiving assistance and support from parents over the past 3 months (AOR = 1.85, 95%CI: 1.12–3.06) were significantly associated with missed doses in the past month. Between the ages of 14–17 years (AOR = 2.66, 95% CI: 1.37–5.16), female (AOR = 2.21, 95% CI: 1.20–4.08), and suboptimal adherence (AOR = 2.45, 95% CI: 1.32–4.57) were significantly associated with virological failure. Conclusions Children’s mental health plays a role in HIV treatment outcomes. Psychological interventions should be promoted in pediatric HIV care clinics to improve children’s mental health status and HIV treatment outcomes.

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18–100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.

BackgroundEmerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings. ObjectiveWe aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022. MethodsThis cross-sectional study was conducted using 2-stage systematic sampling according to the World Health Organization’s surveillance guidelines in 8 provincial-level administrative divisions in 2022. Demographic information and plasma samples were obtained from study participants. PDR was analyzed using the Stanford HIV drug resistance database, and the Tamura-Nei 93 model in HIV-TRACE was used to calculate pairwise matches with a genetic distance of 0.01 substitutions per site. Logistic regression was used to identify and estimate factors associated with PDR. ResultsPDR testing was conducted on 2568 participants in 2022. Of the participants, 34.8% (n=893) were aged 30-49 years, 81.4% (n=2091) were male, and 3.2% (n=81) had prior ARV exposure. The prevalence of PDR to protease and reverse transcriptase regions, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 7.4% (n=190), 6.3% (n=163), 1.2% (n=32), and 0.2% (n=5), respectively. Yunnan, Jilin, and Zhejiang had much higher PDR incidence than did Sichuan. The prevalence of nonnucleoside reverse transcriptase inhibitor–related drug resistance was 6.1% (n=157) for efavirenz and 6.3% (n=163) for nevirapine. Multivariable logistic regression models indicated that participants who had prior ARV exposure (odds ratio [OR] 7.45, 95% CI 4.50-12.34) and the CRF55_01B HIV subtype (OR 2.61, 95% CI 1.41-4.83) were significantly associated with PDR. Among 618 (24.2%) sequences (nodes) associated with 253 molecular transmission clusters (size range 2-13), drug resistance mutation sites included K103, E138, V179, P225, V106, V108, L210, T215, P225, K238, and A98. ConclusionsThe overall prevalence of PDR in China in 2022 was modest. Targeted genotypic PDR testing and medication compliance interventions must be urgently expanded to address PDR among newly diagnosed people living with HIV in China.

Abstract. Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, and it is important to detect early and monitor the disease trend for policymakers to make informed decisions. We explored the predictive utility of Baidu Search Index and Baidu Information Index for early warning of COVID-19 and identified search keywords for further monitoring of epidemic trends in Guangxi. A time-series analysis and Spearman correlation between the daily number of cases and both the Baidu Search Index and Baidu Information Index were performed for seven keywords related to COVID-19 from January 8 to March 9, 2020. The time series showed that the temporal distributions of the search terms “coronavirus,” “pneumonia” and “mask” in the Baidu Search Index were consistent and had 2 to 3 days' lead time to the reported cases; the correlation coefficients were higher than 0.81. The Baidu Search Index volume in 14 prefectures of Guangxi was closely related with the number of reported cases; it was not associated with the local GDP. The Baidu Information Index search terms “coronavirus” and “pneumonia” were used as frequently as 192,405.0 and 110,488.6 per million population, respectively, and they were also significantly associated with the number of reported cases (rs > 0.6), but they fluctuated more than for the Baidu Search Index and had 0 to 14 days' lag time to the reported cases. The Baidu Search Index with search terms “coronavirus,” “pneumonia” and “mask” can be used for early warning and monitoring of the epidemic trend of COVID-19 in Guangxi, with 2 to 3 days' lead time.

Abstract. The human immunodeficiency virus (HIV)–infected population with a transmission link has a strong genetic similarity in viral gene sequences that tend to cluster. In recent years, a strategy for guiding HIV/acquired immunodeficiency syndrome (AIDS) prevention using sequence-based transmission networks has been proposed. The execution of this strategy provides an opportunity to effectively control the spread of the AIDS epidemic in China. HIV molecular transmission network research has been actively pursued by a number of Chinese research groups. Medium- and long-term strategies were created with the goal of using HIV molecular transmission networks to guide targeted prevention and control in China. Technical guidelines for HIV transmission network monitoring and intervention have been written and released. Pilot studies are continuing in the meantime. Despite the fact that this strategy has a bright future, there are still many challenges to overcome to achieve the intended AIDS prevention and control goals.

Abstract. Anti-human immunodeficiency virus (HIV) treatment resistance surveillance has been going on for nearly 18 years in China. In this paper, we review the prevalence in China of resistance to reverse transcriptase and protease inhibitors in the HIV-infected population receiving antiretroviral therapy (ART) and the population that stopped ART in recent years. Drug resistance is an important factor affecting the death of patients with acquired immune deficiency syndrome (AIDS). With the extension of the duration of ART and the expansion of the population receiving ART, especially the widespread promotion of preventive drugs before and after exposure, it is important to obtain insight into the prevalence and types of drug-resistant strains and their impact on the overall AIDS prevention and treatment effect.

Abstract Background Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. Methods We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. Results Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts

Abstract HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count

Abstract Background Antiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART. Methods A retrospective cohort study analysis of 58 239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010–2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH. Results Our study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI) 2.88–3.02] and 5.92 (95% CI 5.82–6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR) = 1.42; 95% CI 1.32–1.54], HCV-co-infected patients had 65% higher mortality (aHR = 1.65; 95% CI 1.47–1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR = 2.23; 95% CI 1.87–2.66). Conclusions HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH. Graphical Abstract

BackgroundNearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes. ObjectiveThis study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China. MethodsWe performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases. ResultsA total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n=5507, 54%); 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n=614, 70.7% vs n=1447, 15.5%; P

BackgroundIn Guangxi province of China, there is a high prevalence of HIV in the general population and in men who have sex with men (MSM). However, there is still a low proportion of MSM among people living with HIV. This apparent contradiction could be due to the high proportion of potential non-disclosed MSM (pnMSM) among reported heterosexual men. We analyzed the genetic linkage of HIV specimens to address this problem aiming to (1) identify the optimal genetic distance threshold, which gave the highest number of genetic clusters, (2) document the proportion of potential non-disclosed MSM (pnMSM) among self-reported heterosexual men, and (3) determine predictors for pnMSM.MethodsPairwise genetic distances were computed among all samples. The genetic distance threshold giving the highest number of genetic clusters was identified. Self-reported heterosexual men were identified as belonging to the pnMSM group if they could be linked to any MSM in their cluster. Multinomial logistic regression was used to determine associated factors of being pnMSM.ResultsThe optimal genetic distance threshold was 0.75% substitutions/site. Among 896 self-reported heterosexual men, the frequency (percentage and 95% confidence interval) was 62 (6.9%, 5.2-8.6%) for pnMSM, 779 (86.9%, 84.7-89.1%) for indeterminate men and 55 (6.1%, 4.5-7.7%) for potential heterosexual men, respectively. Self-reported heterosexual men who were younger, single and more educated were more likely to be pnMSM.ConclusionBased on these findings, there is a need to pay more attention to sexually active, young and educated self-reported heterosexual men and provide them with voluntary counselling and testing and specific HIV prevention services.

Abstract Background Pretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014–2020 in southwestern China. Methods Consecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014–2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR. Results In total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p

Clusters of genetically similar infections suggest rapid transmission and may indicate priorities for public health action or reveal underlying epidemiological processes. However, clusters often require user-defined thresholds and are sensitive to non-epidemiological factors, such as non-random sampling. Consequently the ideal threshold for public health applications varies substantially across settings. Here, we show a method which selects optimal thresholds for phylogenetic (subset tree) clustering based on population. We evaluated this method on HIV-1 pol datasets (n = 14, 221 sequences) from four sites in USA (Tennessee, Washington), Canada (Northern Alberta) and China (Beijing). Clusters were defined by tips descending from an ancestral node (with a minimum bootstrap support of 95%) through a series of branches, each with a length below a given threshold. Next, we used pplacer to graft new cases to the fixed tree by maximum likelihood. We evaluated the effect of varying branch-length thresholds on cluster growth as a count outcome by fitting two Poisson regression models: a null model that predicts growth from cluster size, and an alternative model that includes mean collection date as an additional covariate. The alternative model was favoured by AIC across most thresholds, with optimal (greatest difference in AIC) thresholds ranging 0.007-0.013 across sites. The range of optimal thresholds was more variable when re-sampling 80% of the data by location (IQR 0.008 - 0.016, n = 100 replicates). Our results use prospective phylogenetic cluster growth and suggest that there is more variation in effective thresholds for public health than those typically used in clustering studies.

CRF07_BC is one of the most prevalent HIV-1 strains in China, which contributes over one-third of the virus transmissions in the country. In general, CRF07_BC is associated with slower disease progression, while the underlying mechanisms remain unclear. Our study focused on envelope proteins (Env) and its V3 loop which determine viral binding to co-receptors during infection of cells. We studied a large dataset of 3,937 env sequences in China and found that CRF07_BC had a unique profile of predominantly single CCR5 tropism compared with CCR5 and CXCR4 dual tropisms in other HIV-1 subtypes. The percentages of the CXCR4-tropic virus in B (3.7%) and CRF01_AE (10.4%) infection are much higher than that of CRF07_BC (0.1%), which is supported by median false-positive rates (FPRs) of 69.8%, 25.5%, and 13.4% for CRF07_BC, B, and CRF01_AE respectively, with a cutoff FPR for CXCR4-tropic at 2%. In this study, we identified the first pure CXCR4-tropic virus from one CRF07_BC-infected patient with an extremely low CD4+T cell count (7 cells/mm3). Structural analysis found that the V3 region of this virus has the characteristic 7T and 25R and a substitution of conserved “GPGQ” crown motif for “GPGH”. This study provided compelling evidence that CRF07_BC has the ability to evolve into CXCR4 strains. Our study also lay down the groundwork for studies on tropism switch, which were commonly done for other HIV-1 subtypes, for the long-delayed CRF07_BC.

BackgroundThis study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network.Materials and methodsThis was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016–2018) and those at baseline (2015–2017), respectively.ResultsOf 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48–0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of

ObjectivesWe investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China.MethodsBased on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression.ResultsOf the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25–3.27) and not significantly different (OR: 1.72, 95% CI: 0.87–3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08–5.89).ConclusionThe overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Abstract With the rapid increase in HIV prevalence of men who have sex with men (MSM) in recent years and common human migration and travelling across different provinces in China, MSM are now finding it easier to meet each other, which might contribute to local HIV epidemics as well as fueling cross-province transmission. We performed a cross-sectional survey in 2018–2019 to investigate the current HIV subtype diversity and inferred HIV strain transmission origin among MSM in Guangxi province, China based on a phylogenetic analysis. Based on 238 samples, we found that the HIV-1 subtype diversity was more complicated than before, except for three major HIV subtypes/circulating recombinant forms (CRFs): CRF07_BC, CRF01_AE, CRF55_01B, five other subtypes/CRFs (CRF59_01B, B, CRF08_BC, CRF67_01B, CRF68_01B) and five unique recombinant forms (URFs) were detected. In total, 76.8% (169/220) of samples were infected with HIV from local circulating strains, while others originated from other provinces, predominantly Guangdong and Shanghai. The high diversity of HIV recombinants and complicated HIV transmission sources in Guangxi MSM indicates that there has been an active sexual network between HIV positive MSM both within and outside Guangxi without any effective prevention. Inter-province collaboration must be enforced to provide tailored HIV prevention and control services to MSM in China.

The membrane-proximal external region (MPER) is a promising HIV-1 vaccine target owing to its linear neutralizing epitopes and highly conserved amino acids. Here, we explored the neutralization sensitivity and investigated the MPER sequences in a chronic HIV-1 infected patient with neutralizing activity against the MPER. Using single-genome amplification (SGA), 50 full-length HIV-1 envelope glycoprotein (env) genes were isolated from the patient’s plasma at two time points (2006 and 2009). The neutralization sensitivity of 14 Env-pseudoviruses to autologous plasma and monoclonal antibodies (mAbs) was evaluated. Env gene sequencing revealed that the diversity of Env increased over time and four mutation positions (659D, 662K, 671S, and 677N/R) were identified in the MPER. The K677R mutation increased the IC50 values of pseudoviruses approximately twofold for 4E10 and 2F5, and E659D increased the IC50 up to ninefold for 4E10 and fourfold for 2F5. These two mutations also decreased the contact between gp41 and mAbs. Almost all mutant pseudoviruses were resistant to autologous plasma at both the earlier and concurrent time points. Mutations 659D and 677R in the MPER decreased the neutralization sensitivity of Env-pseudoviruses, providing a detailed understanding of MPER evolution which might facilitate advances in the design of HIV-1 vaccines.

CRF55_01B is a relatively “young” HIV strain. At present, we do not know much about its transmission characteristics in China. So, to describe the transmission characteristics of CRF55_01B strain among provinces and HIV infected people, and to analyze the reasons for its rapid epidemic in China, a total of 1237 subjects infected with CRF55_01B from 31 provinces spanning a period of 12 years from 2007 to 2018 were enrolled in this study. By constructing a molecular network and Bayesian correlation analysis, we found that CRF55_01B increased exponentially from 2005 to 2009 after its origin in Shenzhen, and increased rapidly after 2010. CRF55_01B began to spread to other provinces in 2007. After 2010, the strain showed a trend of rapid spread and epidemic from Guangdong-Shenzhen to other provinces in China. Guangdong, Shenzhen, Hunan, Beijing, Guangxi, Hubei, Jiangxi, Guizhou, Hebei, Anhui, Shanghai, Shandong, Henan, and Yunnan were the key provinces of CRF55_01B transmission. CRF55_01B, although originating from men who sex with men (MSM), was transmitted among heterosexuals in 2010. Males in heterosexuals played a crucial role in the transmission and diffusion of this strain. We also revealed that CRF55_01B might spread rapidly along with the rapid development of the Beijing-Guangzhou and Beijing-Kowloon railways. This study suggests that if we detect the spread of MSMs in time through molecular monitoring in the early stage of the epidemic, it can help us control the epidemic early and prevent its spread, which is of great significance to China's national prevention and control of HIV-1.

Abstract Background The Guangxi Zhuang Autonomous Region bears a relatively high burden of HIV/AIDS infection. The number of accumulatively reported HIV/AIDS cases in Guangxi is the third highest among 31 provinces or Autonomous Region from 2004 to 2007, changed to the second highest between 2011 and 2013, then returned to the third highest again after 2014. We aim to estimate the new infections and evaluate the real-time HIV epidemic in Guangxi, China, in order to reveal the rule of HIV transmission. Methods Firstly, the number of annually reported HIV and AIDS cases, as well as the number of cases linked with CD4 data are extracted from the HIV/AIDS information system in China. Secondly, two CD4-staged models are formulated by linking the with-host information on CD4 level to between-host transmission and surveillance data. Thirdly, new HIV infections, diagnosis rates and undiagnosed infections over time are estimated by using Bayesian method and Maximum Likelihood Estimation method. Results The data reveal that the newly reported cases have been decreasing since 2011, while lots of cases are identified at late CD4 stage. The data fitted results indicate that both models can describe the trend of the epidemic well. The estimation results show that the new and undiagnosed infections began to decrease from the period2006 - 2008. However, the diagnosis probabilities/rates keep at a very low level, and there are still a large number of infections undiagnosed, most of which have a large probability to be identified at late CD4 stage. Conclusions Our findings suggest that HIV/AIDS epidemic in Guangxi has been controlled to a certain extent, while the diagnosis rate still needs to be improved. More attentions should be paid to identify infections at their early CD4 stages. Meanwhile, comprehensive intervention measures should be continually strengthened in avoid of the rebound of new infections.

Abstract Background The aim of this study was to assess trends in drug resistance and associated clinical and programmatic factors at a national level during the rapid scale up of ART. Methods Logistic regression was used to identify the factors associated with HIVDR. Variables associated with drug resistance in multivariable logistic regression were included in the Cochran–Armitage test for trend. Results A total of 11,976 patients were enrolled in the study. The prevalence of HIVDR among patients who received ART for 9–24 months during 2003–2008, 2009–2012, and 2013–2015 significantly decreased (15.5%, 6.3%, and 2.3%, respectively, P

Abstract Background HIV- and MSM-related stigma are well documented as common for Chinese men who have sex with men (MSM) living with HIV, yet there is sparse literature on intimate partner violence (IPV) and its relationship with stigma in this vulnerable population. To evaluate the association between HIV-stigma and stigma related to homosexuality and IPV among newly HIV-diagnosed MSM in China. Methods Data were collected in the baseline survey among newly HIV-diagnosed Chinese MSM in a randomized clinical trial via face-to-face interviews. Univariate logistic and multivariate logistic regression analyses were performed to assess the associations between IPV and HIV- and MSM-related stigma. Results Of 367 newly HIV-diagnosed Chinese MSM, 23.7% experienced any IPV, including 16.6% physical, 7.4% psychological and 5.2% sexual IPV. Positive associations were found between HIV- and MSM-related stigma and IPV. Men with high HIV-related stigma (score ≥ 27) were 1.67 times as likely to experience any IPV as those with low stigma (adjusted odds ratio [AOR]: 1.67, 95% confidence interval [CI]: 1.02–2.76). Men with high MSM-related stigma (score ≥ 6) were 1.99 times as likely to experience any IPV as those with low stigma (AOR: 1.99, 95% CI: 1.18–3.36). Conclusions HIV- and MSM-related stigmas was positively associated with IPV experiences among newly diagnosed MSM in China. The manner in which stigma may exacerbate IPV, and/or the influence of IPV on worsening stigma should be further evaluated. The high prevalence of IPV and stigma in this population suggests that interventions should be taken to reduce stigma and prevent this risky behavior among MSM.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

The prevalence of CRF07_BC is 39.7% and has become the most infectious HIV strain in China. To study the transmission and diffusion trajectory of CRF07_BC in China and to prevent further expansion of its transmission. A total of 16,635 sequences of the CRF07_BC pol gene were collected from 1997-2020. We characterized the gene subtypes according to a phylogenetic tree analysis. A 0.50% molecular network was constructed to analyze the transmission relationship among different provinces for CRF07_BC and its two epidemic clusters. Spatial and temporal propagation characteristics were analyzed according to phylogeographic analysis. Finally, we evaluated the differences in transmission of CRF07_BC-O, and CRF07_BC-N. Our dataset included 8,816 sequences of CRF07_BC-N and 7,819 sequences of CRF07_BC-O. There were 7,132 CRF07_BC sequences in the molecular network, and the rate of clustered was 42.9%. Compared to CRF07_BC-O, CRF07_BC-N showed significantly (P

To control the HIV/AIDS epidemics in Guangxi Zhuang Autonomous Region in China, Guangxi government launched the 5-year Guangxi AIDS Conquering Project (GACP, Phase I: 2010-2014, Phase II: 2015-2020). In the project, three measures are implemented, such as great improvements of the coverage of HIV/AIDS education, promotion of HIV voluntary counseling and testing, and enhancement of antiretroviral treatment. In this paper, we explore the effects of the three measures of GACP by construction of a Susceptible-Infected-Diagnosed-Treated population compartments model and via evaluation of the basic reproduction number derived from the model. A computational framework is developed for estimating the model parameters based on the HIV surveillance data, with application of the Markov-Chain Monte-Carlo method and Nonlinear Least Squares method. By estimating the new infections and evaluating the basic reproduction number, we find that the implementation of the three measures of GACP has a significant effect on controlling the rise of HIV/AIDS cases and the epidemic trend. Compared with HIV voluntary counseling and testing, strengthening HIV/AIDS education and expanding the coverage of antiretroviral treatment show a greater impact on HIV/AIDS epidemic control, which provides a reference project for other provinces with a similar epidemic situation in Guangxi Zhuang Autonomous Region. At the same time, our research fills the current research gap for the evaluation of large-scale AIDS prevention and control projects in developing areas.

Traditional methods of quantifying epidemic spread are based on surveillance data. The most widely used surveillance data are normally incidence data from case reports and hospital records, which are normally susceptible to human error, and sometimes, they even can be seriously error-prone and incomplete when collected during a destructive epidemic. In this manuscript, we introduce a new method to study the spread of infectious disease. We gave an example of how to use this method to predict the virus spreading using the HIV gene sequences data of China. First, we applied Bayesian inference to gene sequences of two main subtypes of the HIV virus to infer the effective reproduction number (GRe(t)) to trace the history of HIV transmission. Second, a dynamic model was established to forecast the spread of HIV medication resistance in the future and also obtain its effective reproduction number (MRe(t)). Through fitting the two effective reproduction numbers obtained from the two separate ways above, some crucial parameters for the dynamic model were obtained. Simply raising the treatment rate has no impact on lowering the infection rate, according to the dynamics model research, but would instead increase the rate of medication resistance. The negative relationship between the prevalence of HIV and the survivorship of infected individuals following treatment may be to blame for this. Reducing the MSM population’s number of sexual partners is a more efficient strategy to reduce transmission per the sensitivity analysis.

To study the characteristics of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hefei, a cross-sectional survey was used to collect 816 samples from newly reported HIV infections from 2017 to 2020 and 127 samples from HIV infections with virological failure from 2018 to 2019 in Hefei. HIV drug resistance levels and drug resistance mutations were interpreted using the Stanford Drug Resistance Database. Molecular networks were constructed by HIV-TRACE. Among the newly reported infections in Hefei, the prevalence of PDR was 6.4% (52/816). The drug resistance mutations were mainly V179E/D/T (12.4%), K103N (1.3%), and V106I/M (1.3%). In addition, it was found that the CRF55_01B subtype had a higher drug resistance rate than other subtypes (p < 0.05). Molecular network analysis found that K103N and V179E may be transmitted in the cluster of the CRF55_01B subtype. The prevalence of ADR among HIV infections with virological failure was 38.6% (49/127), and the drug resistance mutations were mainly M184V (24.4%), K103N/S (15.7%), Y181C (11.0%), G190S/A/E (10.2%), and V106M/I (10.2%). The molecular network was constructed by combining HIV infections with virological failure and newly reported infections; M184V and Y181C may be transmitted between them. The chi-square trend test results indicated that the higher the viral load level, the greater the number of newly reported infections linked to the infections with virological failure in the molecular network. In conclusion, interventions should focus on infections of the CRF55_01B subtype to reduce the transmission of drug-resistant strains. However, improving the treatment effect of HIV infections is beneficial for reducing the second-generation transmission of HIV.

BackgroundChina's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China.MethodsIn the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number [Formula: see text] from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number [Formula: see text] from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting [Formula: see text] to [Formula: see text] by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in [Formula: see text].ResultsBy analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number [Formula: see text] dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025.ConclusionWith the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone.

BackgroundBeijing is a national and international hub potentially containing a broad diversity of HIV variants. Previous studies on molecular epidemiology of HIV in Beijing pooled together samples from residents and non-residents. Pooling residents and non-residents has potentially introduced bias and undermined a good assessment and the intervention among the autochthonous population. Here, we aimed to define HIV subtype diversity and investigate the TDR in Beijing residents exclusively.MethodsWe analyzed the demographic, clinical, and virological data collected between 2001 and 2016 from residents in Beijing. A population-based sequencing of the HIV pol gene was carried out using plasma specimens. Phylogenetic analysis was performed in order to classify sequences into their corresponding subtypes using an automated subtyping tool, the Context-Based Modeling for Expeditious Typing (COMET). Furthermore, the drug resistance mutations were determined using the World Health Organization list for surveillance of TDR mutations.ResultsData on TDR were available for 92% of 2,315 individuals with HIV infection, of whom 7.1% were women. The bioinformatic analysis of HIV strains from this study revealed that a combined 17 subtypes were circulating in Beijing, China between 2001 and 2016. The most common ones were CRF01_AE, CRF07_BC, and subtype B in Beijing during this period. The overall prevalence of TDR was 4.5% (95% confidence intervals[CI]: 3.6%-5.4%), with a declining trend over the period of spanning 2001 through 2016. In-depth class-specific analysis revealed that the prevalence of TDR for the nucleoside reverse-transcriptase inhibitors (NRTIs) was 1.0% (95% CI: 0.6-1.5), 0.9% (95% CI:0.6-1.4) for non-NRTIs and 2.8% (95% CI:2.1-3.5) for protease inhibitors. The prevalence of TDR was lower in individuals infected with the CRF07_BC HIV strain than those infected with CRF01_AE.ConclusionsOur data showed that the HIV epidemic in Beijing displayed a high genetic heterogeneity and a low and declining prevalence of TDR. In sharp contrast to Europe and North America, the declining trend of TDR between 2001 through 2016 was noticed while there was a widespread distribution of antiretroviral treatment in Beijing, China.

Abstract Background The new HIV treatment guidelines in China recommend antiretroviral therapy (ART) for all people living with HIV, but significant gaps in implementation still exist. Pre-exposure prophylaxis (PrEP) can effectively reduce the risk of HIV transmission among men who have sex with men (MSM). This study assessed the epidemiological impact and cost effectiveness of PrEP, enhanced biomedical interventions and their combination among MSM in China. Methods A deterministic mathematical model was developed and projected over 20 years to assess the impact of the PrEP, biomedical interventions and their combinations. Incidence and prevalence of HIV were measured, and cost-effectiveness was assessed using incremental cost (international dollars, Int.$) per quality-adjusted life year (QALY) gained. Results A total of 0.78 million new HIV infections were estimated to occur over the next 20 years if no additional interventions are implemented among MSM. The PrEP-only strategy covering 25–75% of HIV-negative high-risk MSM can prevent 0.09–0.20 million (12.1–25.7%) new infections, at a cost of 17,277–18,452 Int.$/QALY. The optimal cost-effectiveness path is from test-and-treat to the combination strategy of test-and-treat and PrEP. Some strategies could almost eliminate new HIV infections over the next 20 years. Conclusions PrEP, test-and-treat, and their combinations among MSM are effective and cost-effective relative to current policy. PrEP is an important and cost-effective addition to current policy in China.

Background: China has ambitious to achieve significant reductions in HIV transmission and HIV-related mortality by adopting the World Health Organization's “Treat All” approach. Such a prevention strategy is needed future study on regional scale. Methods: An observational cohort study of HIV epidemiology and treatment databases was used to study the effectiveness of antiretroviral therapy on the transmission of HIV in serodiscordant couples in Guangxi of China. Results: A total of 7713 couples were entered into the cohort study analysis which included 1885 couples in the treatment-naive cohort and 5828 couples in the treated cohort. During the follow-up of 18985.29 person-years from 2003 to 2014, the average incidence of HIV was 2.4 per 100 person-years (95% CI 2.1–2.6). HIV seroincidence rate was significantly higher among the treatment naive group (4.2 per 100 person-years, 3.7–4.8) compared with the on treatment group (1.6 per 100 person-years, 1.3–1.8). An overall 45% reduction in risk of HIV transmission among serodiscordant couple was associated with ART treatment (adjusted Hazard Ratio [HR] 0.55, 95% Confidence Interval [CI] 0.44–0.69). Treatment prevention had significantly effectiveness for most baseline characteristics of index partners, such as for male, female, age above 25 years, education below high school, farmer, infected by heterosexual intercourse. Conclusion: Treatment-as-prevention can be implemented in the real-world on a national or regional scale, but ART adherence and comprehensive harm reduction while implementing this strategy require further study. Keywords: HIV, ART, Sero-discordant couples, Transmission, Cohort study

As proposed in the UNAIDSs 2014 report, to end global AIDS epidemic by 2030, 90% of people living with HIV need to be diagnosed, 90% of the diagnosed need to receive antiretroviral therapy (ART), and 90% of those on treatment need to achieve viral suppression (90-90-90 strategy). The strategies focus on the reservoir. It controls HIV spreading by reducing infectiousness of HIV infected individuals via diagnosis and treatment. In this manuscript, we compared the effects of HIV/AIDS interventions that focus on different individuals in MSM population through a dynamics model. Our results showed that, the success or not of the ”90-90-90” strategies depends on a very important factor: the infectious strength among individuals taking ART. Without highly effective HIV treatment, the ”90-90-90” strategies are likely to fail. Therefore, we call for the combination of both primary prevention among the susceptible with the 90-90-90 strategy among the infected to curb the HIV epidemic in Chinese MSM. Keywords: HIV/AIDS, Dynamics model, Prevention and treatment strategies, 2010 MSC: 39A11, 92D30

Hefei, Anhui province, is one of the cities in the Yangtze River Delta, where many people migrate to Jiangsu, Zhejiang and Shanghai. High migration also contributes to the HIV epidemic. This study explored the HIV prevalence in Hefei to provide a reference for other provinces and assist in the prevention and control of HIV in China. A total of 816 newly reported people with HIV in Hefei from 2017 to 2020 were recruited as subjects. HIV subtypes were identified by a phylogenetic tree. The most prevalent subtypes were CRF07_BC (41.4%), CRF01_AE (38.1%) and CRF55_01B (6.3%). Molecular networks were inferred using HIV-TRACE. The largest and most active transmission cluster was CRF55_01B in Hefei’s network. A Chinese national database (50,798 sequences) was also subjected to molecular network analysis to study the relationship between patients in Hefei and other provinces. CRF55_01B and CRF07_BC-N had higher clustered and interprovincial transmission rates in the national molecular network. People with HIV in Hefei mainly transmitted the disease within the province. Finally, we displayed the epidemic trend of HIV in Hefei in recent years with the dynamic change of effective reproductive number (Re). The weighted overall Re increased rapidly from 2012 to 2015, with a peak value of 3.20 (95% BCI, 2.18–3.85). After 2015, Re began to decline and remained stable at around 1.80. In addition, the Re of CRF55_01B was calculated to be between 2.0 and 4.0 in 2018 and 2019. More attention needs to be paid to the rapid spread of CRF55_01B and CRF07_BC-N strains among people with HIV and the high Re in Hefei. These data provide necessary support to guide the targeted prevention and control of HIV.

Abstract Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with 500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40–0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03–1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Abstract Background Heterosexual intercourse accounted for 93% of reported HIV cases in Guangxi, and Guangxi had 10% of China’s total number of reported HIV cases. Older men are particularly vulnerable to STIs, for example, 46% of Guangxi’s HIV cases were men over 50 years of age. As this is an under-studied population in China, effective prevention and control policies have yet to be developed. Thus, the aim of this study was to use a large-scale cross-sectional survey to understand the demographic and behavior factors associated with HIV and syphilis infections among older male clients of female sex workers (FSWs) in a high epidemic area of rural Guangxi, China. Methods A large-scale cross-sectional survey was conducted in 2012 among older male clients of FSWs in low-cost commercial sex venues. Questionnaire interviews were administered to collect sociodemographic and sexual behavior information. Blood samples were collected for HIV and syphilis infection tests. Results Of the 3485 participants, 2509 (72.0%) clients had a steady sex partner and 976 (28.0%) clients had no steady sex partner. The overall prevalence of HIV and syphilis infection were 3.0% and 3.2%, respectively. Compared to those with a steady sex partner, clients with no steady partner had higher odds of HIV infection (AOR: 1.90, 95% CI: 1.27–2.86), syphilis infection (AOR: 1.53, 95% CI: 1.02–2.30), and having factors associated with HIV or syphilis infection, including non-commercial casual sex encounters in last month (AOR: 3.29, 95% CI: 2.42–4.46), >10 years of commercial sex history (AOR: 1.31, 95% CI: 1.12–1.53), >2 incidents of commercial sex in last month (AOR: 1.53, 95% CI: 1.19–1.96), and aphrodisiac use in last month (AOR: 1.40, 95% CI: 1.16–1.70). Clients with no steady partner had lower odds of having heterosexual intercourse (AOR: 0.66, 95% CI: 0.56–0.79), awareness and knowledge of HIV/AIDS (AOR: 0.75, 95% CI: 0.64–0.88), and having had HIV tests (AOR: 0.65, 95% CI: 0.44–0.98). Conclusion Older male clients of low-cost commercial sex venues in rural southwestern China are at high risk for HIV and syphilis infection, especially those with no steady sex partner. Improved interventions are urgently needed for this neglected risk population.

We sought to analyze the evolutionary characteristics and neutralization sensitivity of viruses in a human immunodeficiency virus type 1 (HIV-1) subtype B′ infected plasma donor with broadly neutralizing activity, which may provide information for new broadly neutralizing antibodies (bNAbs) isolation and immunogen design. A total of 83 full-length envelope genes were obtained by single-genome amplification (SGA) from the patient’s plasma at three consecutive time points (2005, 2006, and 2008) spanning four years. In addition, 28 Env-pseudotyped viruses were constructed and their neutralization sensitivity to autologous plasma and several representative bNAbs were measured. Phylogenetic analysis showed that these env sequences formed two evolutionary clusters (Cluster I and II). Cluster I viruses vanished in 2006 and then appeared as recombinants two years later. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs, including 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. We confirmed that HIV-1 continued to evolve even in the presence of bNAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.

Background: As a response to a severe HIV epidemic in the Liangshan Prefecture, one of the worst in China, population based HIV interventions, including two population-wide HIV screening, have been carried out since 2005 at two townships in a remote mountainous region of Liangshan. The objective of our mathematical modeling study is to assess the temporal dynamics of the HIV epidemic in the two townships based on the data collected in the study area during the period 2005â2010. Methods: A mathematical model was set up to describe the population dynamics of HIV transmission in study area. The model was calibrated by fitting it to the HIV testing and treatment data from 2005 to 2008. Validation of the model was done by comparing its predicted value of HIV prevalence in 2010 to the prevalence data obtained in the 2010 population wide HIV testing. The validated model was used to produce estimation of HIV incidence, prevalence and death. Results: Our model estimations show that population-based HIV interventions have significantly slowed down the rise of the HIV epidemic in the two townships. Over the five-year period from 2005 to 2010, the year-over-year rate of increase in HIV incidence, prevalence, and death has declined by 91.5%, 28.7%, and 52.3%, respectively. Conclusion: Mathematical models, when integrated with epidemiological and surveillance data, can be an effective tool for predicting the temporal dynamics of HIV and assessing the impacts of HIV interventions. Keywords: HIV epidemiology, HIV testing and treatment, mathematical modeling

To project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China.A complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)-S1: Male sexual partners decrease (reduced by a random value m from 1-50) while condom use increases (risk constant p is a random value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); S4: Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1-4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use.Partner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient.

HIV drug resistance is associated with faster clinical progression of AIDS. However, the effect of significant polymorphisms and mutational covariation on mortality among HIV/AIDS patients receiving long-term antiretroviral therapy (ART), have rarely been studied.In this prospective cohort study from December 2003 to December 2014, we present a new computational modelling approach based on bioinformatics-based models and several statistical methods to elucidate the molecular mechanisms involved in the acquisition of polymorphisms and mutations on death in HIV/AIDS patients receiving long-term ART in China.This study involved 654 ART-treated patients, who had been followed for 5473.4 person-years, a median of 9.8 years, and 178 died (25.2%, 3.3/100 person-years). The first regimens included AZT/d4T + NVP+ ddI (78.9%) or AZT/d4T + NVP+ 3TC (20.0%). We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that 20 polymorphisms (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, L74I, I93L, K103N, V106A, E169D, Y181C, G190A, Q197K, T200V, T200E, T215I, E224D and P225H) were strongly associated with AIDS related deaths. Among them, 7 polymorphisms (L74I, K103N, V106A, Y181C, G190A, T215I and P225H) were known to be drug resistance mutations, 7 polymorphisms (E6D, E35D, S37N, I93L, E169D, T200V and T200E were considered to be potential drug resistance mutations, and 6 polymorphisms (T39A, K43E, S68N, Q197K, T200V and E224D) were newly found to have an association with drug resistance mutations, which formed a complex network of relationships.Some polymorphisms and mutational covariation may be the important influencing factors in the failure of treatment. Understanding these mechanisms is essential for the development of new therapies, designing optimal drug combinations, and determining effective clinical management of individual patients.

China's National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.A cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.The study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ≥1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.Most patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.

BACKGROUND:The assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied. METHODS:We conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system. RESULTS:In patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4+ cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence. CONCLUSIONS:The hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART.