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Background Treatment as prevention evolved into the universal HIV test-and-treat (UTT) strategy, which entails testing to the general population and treatment to every people living with HIV. We investigated universal testing (UT) performance and its determinants in urban Ethiopia and explore magnitude of late diagnosis and its impact on disease stages. Method We used data from the Ethiopia Population Based HIV Impact assessment (EPHIA), conducted in 2017/2018 which was a cross-sectional and household-based study. For current analysis, we considered self-report first diagnosis to estimate universal testing irrespective of their serostatus and also consider HIV LAg avidity vs viral load vs plasma antiretroviral drug level algorithm to categorize the late diagnosis. We finally evaluate disease stages using CD4 count and viral load. A 2-level multilevel mixed-effect logistic regression model was employed. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with p-value Result Data were collected from 18,926 adults among those 29.4% of people living in Urban Ethiopia were never tested for HIV. Never tested females was 26.4% (95% CI = 25.3; 27.5). Never tested among divorced and widowed were 19.4% (95% CI: 17.3; 21.8) and 28.3% (95% CI: 24.6; 32.2), respectively. Never tested among elderly and youth were high (28.3% among 45–54 years old) to (41.2% among 55–64 years old) to 47.8% among 15–24 years old. Overall, late HIV diagnosis among adults in urban Ethiopia was 25.9% (95% CI: 21.7, 30.2). Late diagnosis varies by region ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. Advanced immune suppression (CD4 count Conclusion With the aim of UT for high risk and priority population, the low rate of HIV testing among widowed, elderly, young adolescent and women in urban Ethiopia calls for enhanced HIV testing. Moreover, the low HIV testing and high late diagnosis among the high-burden regions calls for region-specific intervention. Advanced disease stages as a result of the high proportion of late diagnosis may impact on fueling community transmission and hinder treatment outcome among PLHIV.

What is already known about this topic? With increasing coverage of antiretroviral therapy (ART) for HIV-infected patients, more and more attention has been paid to the impact of HIV drug resistance on death in those patients in China. What is added by this report? Among HIV-infected patients receiving ART, the risk of death is higher in patients with HIV drug resistance [adjusted odds ratio (AOR)=4.25, 95% confidence interval (CI): 2.10–8.62], with viral load ≥1,000 copies/mL but drug resistance untested (AOR=4.65, 95% CI: 1.74–12.39), and with neither viral load nor drug resistance being tested (AOR=17.52, 95% CI: 8.73–35.19) when compared with drug-sensitive patients. What are the implications for public health practice? It is important to strengthen drug resistance monitoring and prevention in HIV-infected patients. While performing ART for HIV-infected patients, viral load testing and drug resistance testing should be carried out routinely and promptly.

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.

Background: Pretreatment drug resistance (PDR) poses an increasing threat to the success of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR among HIV patients in an area in Southwest China with extensive drug trafficking. Methods: Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance was analyzed using a genetic transmission network. Results: HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV- 1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others (1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1- 3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was 1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI: 1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis. Conclusions: The results show a moderate overall level of PDR prevalence and rapidly growing drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic among drug users, and surveillance is urgently needed to monitor the trend of PDR.

The aim of this study was to evaluate HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia.A total of 699 adults infected with HIV (aged ≥15 years) who failed first-line Antiretroviral Therapy (ART) were recruited between 2017 and 2019 from 63 ART-providing sites in Ethiopia. Treatment failure was defined as patients with two consecutive viral loads (VLs) ≥1000 copies/mL within six months of follow-up. The pol gene region of HIV-1 was amplified and sequenced using an in-house assay of the Chinese Center for Disease Prevention and Control. The Stanford HIVDB v9.0 algorithm was used for identification of resistance mutations. Resistance mutations were characterized according to the 2019 International AIDS Society-USA mutation list. P values of0.05 were considered statistically significant during multivariate analysis, which was done using SPSS v26.0 (SPSS Inc., Chicago, IL).Overall, HIV drug resistance (HIVDR) among patients failing first-line therapy in Ethiopia was 77.8%. Non-nucleoside/tide reverse transcriptase inhibitors (NNRTI) and NRTI resistance were 75.7% and 71.2%, respectively. Neverapine (NVP) and Efavirenz (EFV) accounted for 74.2% and 60.8% of HIVDR, respectively. About half (48.1%) of NRTI-associated mutations were responsible for Abacavir resistance, while 34% were responsible for multi-NRTI resistance. Mutations responsible for resistance to the commonly used EFV and NVP accounted for 62.9%, while resistance to Etravirine, Doravirine, and Rilivirine, which were not part of the country's ART program, were 37.1%, and can be explained by cross-resistance within the drug class. Protease Inhebitor(PI)associated resistance was detected in only 1.6% of the study's participants. The most common mutations identified were M184V (30.1%), K103N (18.7%), Y181C (13.6%), and K65R (12.1%). In a multivariate logistic regression analysis, predictors of HIVDR were prior ART exposure (adjusted odds ratio [AOR] = 2.3; 95% confidence interval [CI] = 1.8, 3.6), absence of HIV status disclosure (AOR=2.05; 95%CI=1.26, 3.35), CD4 count of ≤200 cells/mmThe high-levels of HIVDR among patients with failure of first-line ART in Ethiopia calls for individualized HIVDR testing. Mutations associated with multi-NRTI and NNRTI cross-resistance may alert the program for considering drugs of higher genetic barrier targeting protease and other regions. Patients with low CD4 count and those who are bedridden should be given special attention for the potential development of HIVDR during clinical management.

While antiretroviral therapy (ART) has been rapidly scaled-up among the population living with human immunodeficiency virus or acquired immune deficiency syndrome (HIV/AIDS) patients since 2016, pretreatment drug resistance (PDR) has also increased.PDR has an impact on ART outcomes. After one year of ART, the risk of virological failure in individuals with PDR was found to be 2.3 times higher than that of individuals without PDR. Moreover, patients with PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) had an even higher risk of virological failure, with an odds ratio of 2.8 as compared with those without PDR.PDR is associated with an increased risk of virological failure. It is recommended to regularly implement PDR monitoring in order to provide information to optimize ART regimens and to prevent HIV drug resistance.

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 μL (AOR 3.8, 95% CI 2.6–5.5, p μL (AOR 5.8, 95% CI 4.6–7.4, p Conclusion Persistent with VL 50–999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts μL, which suggest resistance monitoring and ART optimization be earlier considered.

Owing to the increasing prevalence of HIV-1 CRF01_AE, it is necessary to understand the neutralization properties of CRF01_AE and to develop broadly neutralizing monoclonal antibodies (bnmAbs) that can neutralize this virus. The full-length Env gene was cloned from HIV-1 CRF01_AE-infected plasma specimens collected in China and used to establish pseudoviruses. Neutralization phenotypes of the pseudoviruses were characterized with bnmAbs. The neutralizing activities of 11 bnmAbs VRC01, VRC03, IgG1b12 and 3BNC117 (targeting the CD4 binding site); PG9 (targeting the V1V2 region); 2G12 (targeting the high mannose patch), PGT135 and 10-1074 (targeting the V3 glycans); 2F5, 4E10 and 10E8 (targeting the membrane proximal external region), against 36 pseudoviruses were analyzed, demonstrating varying efficacies. In general, VRC01, 10E8 and 3BNC117 showed strong neutralizing activity, neutralizing more than 75% of the pseudoviruses; followed by PG9 and 4E10, showing moderate neutralizing activity with neutralization of 50%–60% of the pseudoviruses; whereas the efficacies of the remaining bnmAbs were poor, neutralizing less than 15% of pseudoviruses tested. Env variants of CRF01_AE from one infection also showed significant differences in resistance to neutralization. These characterized HIV-1 CRF01_AE pseudoviruses could be used for neutralization studies and evaluation of vaccines or anti-HIV-1 products in China.

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-infected 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 by 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 patients were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that to NRTI (1.7%) and PI (1.2%) (p

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.

Objectives Human immunodeficiency virus (HIV) quasispecies diversity presents a large barrier to the eradication of HIV. The aim of this study was to investigate intrahost HIV quasispecies diversity and evolutionary patterns underpinning the mechanisms of viral pathogenesis during antiretroviral therapy (ART). Methods Forty-five participants with HIV-1 infection were enrolled in a follow-up cohort for >84 months in 2004, and received a lamivudine-based first-line ART regimen. Blood samples were collected every 6 months to measure viral load and CD4+ cell count. Ultra-deep sequencing and phylogenetic analysis were used to characterize the dynamics governing quasispecies diversity of HIV-1 circulating between plasma RNA and cellular DNA of participants with treatment failure (TF, n = 20) or virologic suppression (VS, n = 25). Results Analysis of the distribution of intrahost single-nucleotide variations (iSNVs) and their mutated allele frequencies revealed that approximately 65% of the quasispecies co-occurred in plasma HIV RNA and cellular DNA either before or after ART. The number and frequency of iSNVs are more representative of intrahost HIV diversity, and have better generalizability than phylogenetic inference by measurement of phylogenetic associations. Furthermore, drug-resistance-associated mutations (DRAMs) accumulated to high levels, dramatically increasing the DRAM-to-total-mutation ratio for TF patients. Linear regression analysis revealed that emergent mutations accumulated faster in TF patients compared with VS patients, at a rate of 0.02 mutations/day/kb. Conclusions Based on iSNV analysis, the results demonstrate the dynamics of intrahost HIV quasispecies diversity in patients on ART, and provide a novel insight into the persistence of HIV and development of DRAMs.

To assess whether human immunodeficiency virus type 1 (HIV-1) genotype influences baseline CD4+ T lymphocyte (CD4+) cell count and mortality of patients. The study was conducted from 2014 to 2019 in Guangxi, China, and included 2845 newly diagnosed HIV patients. We used a median regression model to compare CD4+ cell counts in patients newly diagnosed with different HIV-1 genotypes, and a Cox regression model to analyze the associations between HIV-1 genotypes and mortality before and after antiretroviral treatment (ART). In newly diagnosed HIV patients, the baseline CD4+ cell counts of patients with CRF01_AE were significantly lower than those of patients with CRF07_BC, CRF08_BC, and other genotypes. Compared with CRF01_AE, patients infected with CRF07_BC (hazard ratio, 0.55; 95% CI 0.36–0.85), CRF08_BC (hazard ratio, 0.67; 95% CI 0.52–0.85), or other genotypes (hazard ratio, 0.52; 95% CI 0.29–0.94) had significantly lower mortality rates before ART. There were no significant associations between different HIV-1 genotypes and mortality after ART. HIV-1 genotype significantly influences baseline CD4+ cell count and mortality before ART in newly diagnosed HIV patients. We find no significant difference in the outcome of death after ART in patients with different HIV-1 genotypes.

In this study, we identified a novel circulating recombinant form (CRF) of HIV (CRF105_0108) in a total of five patients with no obvious epidemiological linkage in Sichuan, China. Four strains were found in this study, and another strain (XC2014EU01) was reported in a previous study. The phylogenetic analysis of the five near full-length genomes showed that a CRF08_BC segment was inserted into the CRF01_AE backbone with one recombinant breakpoint in the pol region, which is the first HIV-1 CRF of CRF01_AE and CRF08_BC. Three genetic sequences had drug-resistant mutations, E138Q and V179D, indicating that there were low resistance levels to efavirenz (EFV) and nevirapine (NVP) in Liangshan Yi Autonomous Prefecture. CRF105_0108 increases the diversity and complexity of the prevalent HIV-1 CRFs in Sichuan. Simultaneously, drug-resistant mutations in this CRF may influence the efficacy of highly active antiretroviral treatments (ARTs) in Liangshan Yi Autonomous Prefecture.

BackgroundThe 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.MethodsLogistic 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.ResultsA 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 P ConclusionsOur results provide evidence for the effectiveness of China’s “Treat All” approach to guide policy makers to improve training for healthcare providers and education on ART adherence among patients.

Background: WHO has recommended that antiretroviral therapy be provided to all HIV patients to reduce future HIV transmission at the population level. Aside from the HPTN 071 (PopART) community based randomized trial which indicated that universal testing and treatment can reduce HIV incidence at the population level, such a public health strategy has not previously been studied in real-world settings. Methods: In this longitudinal phylogenetic-network study in Guangxi, China, the longitudinal baseline and follow-up data was collected from HIV patients in 2014 and newly diagnosed HIV patients from 2015 to 2018, respectively. We used a genetic distance threshold of 0.75% to analyze the proportions of genetic linkage between annual newly diagnosed HIV patients with HIV patients at baseline stratified by treatment. Findings: Among 804 newly diagnosed HIV patients during 2015-2018, 399 (49.6%) of them genetically linked to HIV patients at baseline during 2014-2017. The overall proportion of genetic linkage between newly diagnosed HIV patients during 2015-2018 with untreated and treated HIV patients at baseline during 2014-2017 was 6.2% and 2.9%, respectively. The prevention efficacy in HIV transmission for treated HIV patients was 53.5% (95% CI: 42.0%-65.0%). There was no significant reduction in HIV transmission among treated HIV patients on dropout or with missing viral load measures. Interpretation: Combined with the HPTN 071 (PopART) study, our study results strongly support the feasibility of treating all HIV patients for future reductions in HIV transmission at the population level in real-world settings. Comprehensive intervention prevention programs are urgently needed. Funding Statement: This study was supported by the Guangxi Science and Technology Bureau (Grant AB16380213), Guangxi Medical and Health Project (Z20170126), National Natural Science Foundation of China (Grants 11971479, 81460510 and 81360442), Guangxi Bagui Honor Scholarship, Ministry of Science and Technology of China (2018ZX10721102-006, 2018ZX10715008), and Chinese State Key Laboratory of Infectious Disease Prevention and Control. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The institutional review board (IRB) of the Guangxi CDC approved this study.

Mingze Su,1 Lingjie Liao,2 Hui Xing,2 Shuai Wang,1,3 Yutang Li,4 Wei Lu,1,5 Lingyuan He,1 Juan Deng,1 Yiming Shao,2 Tong Li,1 Hui Zhuang1 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; 2State Key Laboratory of Infectious Disease Prevention and Control, National Centre for AIDS/STD Control and Prevention, Chinese Centre for Disease Control and Prevention, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, Beijing 102206, China; 3Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing 100191, China; 4Key Laboratory of Medical Molecular Virology of Ministries of Health and Education, Shanghai Medical College, Fudan University, Shanghai 200032, China; 5Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China Purpose: This study aimed to investigate the HIV and hepatitis B virus (HBV) co-infection in three HIV high endemic areas with different modes of HIV transmission and explore the HBV nucleos(t)ide analogue resistance (NUCr) substitutions in this cohort receiving antiretroviral therapy (ART). Patients and methods: The enrolled 705 HIV-infected patients were from three different regions in China and received lamivudine-based ART for at least 1 year. After screening for hepatitis B surface antigen (HBsAg), the hepatitis B e antigen (HBeAg), and antibody against hepatitis B core antigen (anti-HBc and anti-HBc IgM), HBV DNA in plasma of patients positive for HBsAg was tested. The reverse transcriptase (RT) sequences of HBV were analyzed by direct sequencing. Results: The overall HBsAg-positive rate was 7.1% (50/705) (Guangxi [25/170, 14.7%], ­Xinjiang [13/257, 5.1%], and Henan [12/278, 4.3%]). The age, transmission route, and ethnic status were found to be associated with HIV/HBV co-infection. We obtained 23 HBV RT sequences belonging to genotypes B (9/23, 39.1%), C (13/23, 56.5%), and D (1/23, 4.4%). About 65.2% (15/23) of RT sequences harbored NUCr substitutions, all of which had combination substitution patterns. Patients with HBV NUCr had significantly higher HBV DNA level and ratio of HBeAg-positive than those without NUCr. None of the patients was found to have both lamivudine-resistant HBV and HIV. Conclusion: Our results suggested that HBsAg-positive rate in the studied patients was similar to that of the general population in each of the studied regions, where the age, transmission route, and ethnic status might also play roles in HIV/HBV co-infection. The HBV combination NUCr substitutions were common in co-infected patients under ART. Monitoring of HBV infection and NUCr substitutions in HIV-infected patients would help in providing better clinical decisions and management, thus lowering patients’ risks to develop end-stage liver diseases. Keywords: human immunodeficiency virus, hepatitis B virus, co-infection, nucleos(t)ide analogue resistance, hepatitis B surface antigen

We reported a novel HIV-1 circulating recombinant form (CRF) among three epidemiologically unlinked patients through men having sex with men in Hebei Province, China. It was named CRF103_01B (this is temporary as we have not received the CRF number from HIV databases). A near full-length genome phylogenetic tree showed that CRF103_01B was generated by three B (Western origin) segments and CRF01_AE that was described as cluster 5 lineage of CRF01_AE (CRF01-5). The emergence of CRF103_01B increased the complexity of the HIV-1 epidemic in China.

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 &lt, 0.001) and 1% (v.s. Sanger, p &lt, 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 &lt, 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at &gt, 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%.

In this research, we reported a new second generation recombinant form (GXDY460B) between circulating recombinant form (CRF)01_AE and CRF07_BC in a seroconversion couple who obtained the virus from her husband by heterosexual behavior. The analysis result of the near full-length genomic characterization showed that the genome comprises at least 12 interlaced segments, including six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. Cocirculation of multiple virus subtypes and multiple infection routes have existed for a long time in Guangxi, but the recombinant strain was rarely reported among heterosexual transmission population because of its lower crowd confounding degree than men who have sex with men and injecting drug user population. It is the first time that the unique recombinant form (URF) between CRF01_AE and CRF07_BC was identified among heterosexual transmission in Guangxi. The emergence of the novel recombinant helps to understand the pattern of the URF virus.

BACKGROUND Recent studies have suggested that CD4 cell count monitoring has little added value in patients who are virologically suppressed and immunologically stable if viral load (VL) testing is routinely available. These conclusions have not been directly assessed using mortality rate as a study end point in a real-world setting. METHODS This human immunodeficiency virus (HIV) treatment cohort study from 2008 to 2014 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between the frequency of CD4 cell counts and VL testing and death. RESULTS Compared with monitoring CD4 cell counts ≥3 times during the first year of antiretroviral therapy (ART) initiation, as currently suggested by the Chinese National Free Antiretroviral Treatment Program, monitoring them less than twice during the first year of ART was significantly associated with death; however, monitoring them twice in that year did not significantly increase mortality rates. Compared with testing VL at least once during the first year of ART, as currently suggested by the National Free Antiretroviral Treatment Program, performing no VL tests in the first year after ART initiation was significantly associated with higher mortality rates. Routine CD4 cell count monitoring did not have an impact on mortality rates among HIV-infected patients with VLs

We report here two novel HIV-1 recombinant forms (CRF01_AE/B) isolated from two HIV-positive male subjects infected through homosexual contact in Beijing, China. Recombination contributes substantially to the genetic diversity of HIV-1, and is likely to occur in populations in which multiple subtypes circulate. Molecular epidemiological studies showed that subtype B, CRF01_AE, and CRF07_BC are currently cocirculating in parallel among men who have sex with men (MSM) in China, providing the opportunity for the emergence of new recombinants. Phylogenetic analysis of near full-length genome (NFLG) sequences showed that the unique recombinant forms (URFs) were composed of gene regions from CRF01_AE and subtype B. The CRF01_AE region of the recombinants clustered together with a previously described cluster 4 lineage of CRF01_AE. The B regions of both the recombinants clustered within the B strains. The two recombinants were quite similar with six breakpoints in common. These data highlight the importance of continuous surveillance of the dynamic change of HIV-1 subtypes and new recombinants among the MSM population.

We report two different unique HIV-1 recombinant viruses from two HIV-positive men who have sex with men (MSM) in Beijing, China. Phylogenetic analysis of near full-length genomes (NFLG) showed that the unique recombinant forms (URFs) were comprised of gene regions from two circulating recombinant forms, CRF01_AE and CRF07_BC, both common in China. The parental CRF01_AE region of the recombinants clustered together with a previously described cluster 4 lineage of CRF01_AE. The CRF07_BC regions of both the recombinants clustered within the CRF07_BC radiation, but were distinct from other CRF07_BC reference sequences. The two recombinant forms had two breakpoints in common. The emergence of the two URFs indicates the ongoing generation of recombinant viruses involving CRF01_AE and CRF07_BC, and may provide insight into our understanding of the dynamics and complexity of the HIV-1 epidemic in China.

ObjectiveTo explore factors associated with HIV virological failure (VF) and HIV drug resistance (HIVDR) among HIV-positive Chinese individuals 4 years after initiating first-line lamivudine-based antiretroviral treatment (ART) in 2008 at five sentinel sites.DesignFirst-line ART initiators who were previously treatment naïve were selected using consecutive ID numbers from the 2008 National Surveillance Database into a prospective cohort study. Questionnaires and blood samples were collected in 2011 and 2012 to assess the outcomes of interest: VF (defined as viral load ≥1000 copies/mL) and HIVDR (defined as VF with genetic drug-resistant mutations). Questionnaires and data from National Surveillance Database assessed demographics and drug adherence data.Results536 individuals with HIV were analysed; the 4-year risk of VF was 63 (11.8%) and HIVDR was 27 (5.0%). Female participants initiating stavudine (D4T)-based regimens were more susceptible to both VF (adjusted OR (aOR)=2.5, 95% CI 1 to 6.1, p=0.04) and HIVDR (aOR=3.6, 95% CI 1 to 12.6, p=0.05) versus zidovudine-based regimens. Male participants missing doses in past month were more susceptible to both VF (aOR=2.8, 95% CI 1.1 to 7, p=0.03) and HIVDR (aOR=9.7, 95% CI 2.1 to 44.1, pConclusionsOur findings suggest successful treatment outcomes at 4 years for roughly 90% of patients. We suggest conducting further study on whether and when to change ART regimen for women initiated with D4T-based regimen, and reinforcing adherence counselling for men. Increased VF and HIVDR risk among non-Han minorities warrants further exploration, and ethnic minorities may be an important group to tailor adherence-focused interventions.

The seroprevalence of hepatitis E virus (HEV) in HIV-infected patients in China has never been reported. Thus, anti-HEV in HIV-infected patients recruited in five provinces in China was tested. The seroprevalence of HEV was 39.7%, which was higher than that in the general population (23.5%). HEV infection might be a frequent cause of hepatitis in HIV-infected patients.

To investigate the prevalence and temporal trend of transmitted drug resistance (TDR), a nationwide cross-sectional survey was conducted among 5627 ART naïve newly diagnosed HIV-infected individuals in 2015 in China. Totally 4704 partial pol sequences were obtained. Among them, the most common HIV-1 circulating recombinant form (CRF) or subtype was CRF01_AE (39.0%), followed by CRF07_BC (35.6%), CRF08_BC (8.9%), and subtype B (5.5%). TDR mutations were found in 3.6% of the cases, with 1.1% harboring TDR to protease inhibitors (PIs), 1.3% having TDR to nucleoside reverse transcriptase inhibitors (NRTIs), and 1.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs). No significant difference was found in the prevalence of TDR, as compared with the results of another nationwide survey performed among ART naïve HIV-infected people in between 2004 and 2005, except in the 16–25 year-old group. In addition, four drug-resistant transmission clusters were identified in phylogenetic trees, accounting for 6.2% (9/145) of the individuals with TDR. Although the rate of TDR remained relatively low in the past 10 years in China, surveillance is still needed to monitor the trend of TDR and to optimize the first-line regimens.

Background: Compensatory mutations have been observed to emerge with drug resistance (DR) mutations, but their effects on virological response to treatment have not been fully examined. In this study, we characterized the emergence and depletion dynamics of a compensatory mutation K43E that correlated with primary nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in Chinese HIV patients on antiretroviral treatment. Method: Single Genome Amplification (SGA) was used to obtain the HIV-1 pol gene quasispecies in three patients over 6 years of Antiretroviral Therapy (ART) treatment. SGA sequences were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with molecular clock to identify and track compensatory mutation K43E correlated with primary DR mutation M41L. We evaluated the relationship between potential compensatory mutation and DR mutations through Ka/Ks ratio, Jaccard similarity coefficient, and compared these with concurrent viral load data. Conclusion: We determined that a known compensatory mutation, K43E, frequently co-occurs with the drug resistance mutation M41L and may offer a significant advantage in the long-term survival of such drug resistant strains.

We report here a novel HIV-1 circulating recombinant form (CRF62_BC) that was isolated from three epidemiologically unlinked individuals [one from an injecting drug user (IDU); two from heterosexuals] in Dehong prefecture of western Yunnan province. CRF62_BC harbored two subtype B segments in the pol and vpu-env regions in a subtype C backbone. Subregion tree analysis demonstrated that subtype B regions originated from a Thai-B (subtype B') lineage and the subtype C region was from an India C lineage. CRF62_BC is the fourth CRF composed of subtypes B' and C known to date after CRF07_BC, CRF08_BC, and CRF57_BC, which were originally found among IDUs in China. The emergence of CRF62_BC may indicate the continual generation of new recombinant strains in various high-risk populations in western Yunnan. This may complicate the development of effective vaccines to limit the HIV-1 epidemic and increase the difficulty of AIDS prevention and control in China.

We report a novel HIV-1 circulating recombinant form (CRF64_BC) that was isolated from five epidemiologically unlinked HIV-infected persons in Yunnan province. CRF64_BC was composed of subtype B and subtype C, with five short subtype B segments inserted into the subtype C backbone. Phylogenetic analysis demonstrated that the C subregion was correlated with the India C lineage, which was transmitted into China in the early 1990s. The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results. Dehong is considered the epicenter of HIV-1 in China, and recombinant strains such as CRF07_BC and CRF08_BC, which also originated from this region, have spread widely in China. The newly emerged CRF64_BC increases the complexity of the HIV epidemic in China and complicates the development of subtype-specific tools against HIV transmission.

Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insights into the dynamics of human immunodeficiency virus type 1. We built a simple mathematics model to study the effect of latent-infected resting memory CD4+ T cells during the HIV infection and highly active anti-retroviral therapy (HAART). Through analysis of eight patients who received HAART in China, we have an insight into the mechanisms of resting memory CD4+ T cells in HIV infection. Simulations show that new infections still exist in the eight patients even under the HAART. Also, because of the long half-life of resting infected memory CD4+ T cells, removal of HIV from patient could take considerably longer time or be unattainable.

Objectives To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China. Design We recruited 365 patients on cART in two rural Chinese counties in 2003-2004 and followed them every 6 months until May 2010. Methods Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan-Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality. Results At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈ 18-month median interval between each adverse milestone). Being male, having a baseline CD4 cell count of less than 50 cells/μl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01-3.48). Conclusion HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.

OBJECTIVES To understand the effect of HIV-1 drug resistance mutations in the context of antiretroviral therapy (ART), we compared the prevalence of protease (PR) and reverse transcriptase (RT) mutations in HIV-1 CRF07_BC sequences from blood samples of treatment-naive and ART-treated patients. METHODS Mutation covariation in the RT and PR of HIV-1 CRF07_BC viruses from 542 treatment-naive patients and 261 patients treated with lamivudine/zidovudine/nevirapine or lamivudine/zidovudine/efavirenz was analysed. Stratified networks were used to display the mutation covariation. RESULTS Based on the comparison between treatment-naive and ART-treated patients, three types of featured mutations for RT and PR were initially identified: treatment-associated mutations, treatment-agonistic mutations and overlapping polymorphisms. Twelve significant covariation pairs were found between five treatment-associated mutations (K103N, M184V, Q197K, G190A and Y181C) and nine overlapping polymorphisms (A36E, D39N, Y121H, D123E, R135I, T200A, R277K, L283I and D291E). Meanwhile, three covariation pairs between three treatment-associated mutations (I132L and M184V for RT and I15V for PR) and three overlapping polymorphisms (L10I, L36M and A71V) for PR were also detected. Finally, the overlapping polymorphisms for RT and PR were both found to have significant correlations with treatment-associated mutations, indicating a possible association between polymorphisms and drug resistance. When compared with HIV-1 subtype B under the same regimens as CRF07_BC, the mutation covariations of CRF07_BC showed a distinct pattern of RT and PR mutation covariation. CONCLUSIONS The role of polymorphisms in the development of drug resistance has been widely reported. Here, we found a significant correlation between overlapping polymorphisms for RT and PR and treatment-associated mutations, indicating that polymorphisms exert a global influence on treatment-associated mutations. Polymorphism mutations might therefore be considered before initiating ART to improve the efficacy of drug combinations.

Fitness is a key parameter in the measurement of transmission capacity of individual drug-resistant HIV. Drug-resistance related mutations (DRMs) T369V/I and A371V in the connection subdomain (CN) of reverse transcriptase (RT) occur at higher frequencies in the individuals experiencing antiretroviral therapy failure. Here, we evaluated the effects of T369V/I and A371V on viral fitness, in the presence or in the absence of thymidine analogue resistance-associated mutations (TAMs) and assessed the effect of potential RT structure-related mechanism on change in viral fitness. Mutations T369V/I, A371V, alone or in combination with TAMs were introduced into a modified HIV-1 infectious clone AT1 by site-directed mutagenesis. Then, experiments on mutant and wild-type virus AT2 were performed separately using a growth-competition assay, and then the relative fitness was calculated. Structural analysis of RT was conducted using Pymol software. Results showed that T369V/I severely impaired the relative virus fitness, and A371V compensated for the viral fitness reduction caused by TAMs. Structural modeling of RT suggests that T369V/I substitutions disrupt powerful hydrogen bonds formed by T369 and V365 in p51 and p66. This study indicates that the secondary DRMs within CN might efficiently damage viral fitness, and provides valuable information for clinical surveillance and prevention of HIV-1 strains carrying these DRMs.

To understand the efficacy of antiviral therapy on prevention of HIV transmission and to assess the feasibility of treatment-as-prevention strategy in public health practice, among sero-discordant couples in Guangxi Zhuang autonomous region (Guangxi).Data was gathered through the AIDS prevention and control information system in Guangxi from January 1, 2008 to December 31, 2014, on HIV sero-discordant couples. Time-dependent Cox Model was used to analyze the efficacy of antiviral treatment.A total of 7 694 sero-discordant couples were followed and 394 appeared positive from those negative spouses. The overall HIV positive seroconversion rate was 2.5 (2.2-2.7) /100 person-year. The HIV positive sero-conversion rates were 4.3 (3.7-4.8) /100 person-year in the untreated cohort and 1.6 (1.4-1.9) per 100 person-year in the treated cohort. Rate of HIV transmission declined by 51% in the treated cohort (HR=0.49, 95%CI: 0.40-0.60) but appeared as 45% (AHR=0.55, 95%CI:0.43-0.69) after adjusting for factors as sex, age, education, marital status, occupation, transmission route and baseline CD4(+)T lymphocyte cell count. The rate of reduction in transmission was significant among couples in which the HIV-positive spouses showing the following features as: aged ≥25 years, married, farmers, with educational level of junior high school or below, baseline CD4(+)T lymphocyte cell count500 cells/mm(3) and infection was through heterosexual intercourse.Antiviral therapy as a prevention strategy among sero-discordant couples seemed feasible and effective in Guangxi. Expansion of the coverage on antiviral therapy would reduce the spread of HIV in married couples.

In 2003, antiretroviral therapy became available free of charge in China's public health sector. During 2008 and 2009, 10 surveys to classify transmitted human immunodeficiency virus drug resistance (HIVDR) were conducted in 7 regions in 5 provinces (autonomous regions and municipalities) according to World Health Organization guidance. In 2008, transmitted HIVDR was classified as low (

Pakistan is experiencing a growing HIV epidemic. Antiretroviral drugs (ARV) have been smuggled into the country and available without prescription since the early 1990s, but are now provided free of cost by the government. We assessed the prevalence of HIV-1, drug resistance, and subtype distributions. Blood specimens were collected from HIV-1-infected participants registered in Sindh Province on dry blood spot (DBS) cards in 2008. Pol, protease, and partial reverse transcriptase regions were sequenced after reverse transcriptase PCR (RT-PCR). HIV-1 subtype was assigned by phylogenetic analysis. Primary drug resistance was analyzed by the Calibrated Population Resistance (CPR) tool using the Stanford Surveillance Drug Resistance Mutation (SDRM) major mutation list. Out of 100 blood samples collected, 42 were suitable for testing. Out of 42, 11 were ARV-receiving and 31 ARV-naive patients. Among them, 24 were injection drug users (IDUs), four immigrants, two hijras (male transvestites), two men who have sex with men (MSM), four prisoners, one female sex workers, two spouses of HIV-infected persons, and four from the general population. ARV resistance among naive patients was 2/31 (6.5%) and 36.4% (4/11) among ARV-experienced patients making an overall resistance of 14.2%. HIV-1 subtype A1 was the predominant subtype found in 35/42 (83.3%) followed by CRF35_AD and C, 6.5% each. Subtype D and G were found in one (2.4%) each. A significant proportion of Pakistani HIV patients has ARV drug resistance. Physicians treating patients should consider the magnitude of drug resistance while selecting regimens, and address drug adherence aggressively.

Summary Objective To evaluate HIV drug resistance (HIVDR) among Chinese patients with HIV receiving first-line highly active antiretroviral therapy (HAART). Methods Based on the WHO HIVDR surveys, a prospective cohort study with 12-month follow-up was conducted to estimate the prevalence of HIV RNA

To investigate the responses to switching to second-line regimens among patients who had received a long-term first-line antiretroviral therapy. Patients switching to second-line regimens from June 2008 to June 2015 were enrolled from an observational cohort. In addition, patients continuing first-line therapy and had a viral load

HIV-1 CRF07_BC is one of the predominant strains in China, however, there have been few reports about the genetic characteristics of accessory genes of this strain. In this study, 236 CRF07_BC tat exon-1 regions were obtained by nested PCR and were followed by sequencing. Our results showed some variations in crucial functional domains, especially in the basic region. There were two conserved amino acid variations in the 1 approximately 56 aa fragment of tat gene exon-1 of 07_BC isolates, which were R7N (71.6%) and R46F (90.3%), as compared with subtype B' strains in Thailand. The analysis of the sequences provides some valuable information for an exploration of the predominance of the HIV-1 CRF07_BC epidemic.

BACKGROUND: Transmission of HIV drug resistance (TDR) gives rise to reduced efficacy of initial antiretroviral treatment and has become a public health concern. METHODS: A nationwide survey on TDR was conducted in antiretroviral therapy-naive HIV-1-infected individuals from September 2004 to October 2005 in China. Drug resistance genotyping was performed on subjects plasma samples. Drug resistance mutations were determined and scored by Stanford HIV Drug Resistance algorithm. RESULTS: Sequences were obtained from 676 individuals of whom 61.2% were former plasma and blood donors 17.3% were infected sexually and 17.2% were intravenous drug users. Subtype B HIV-1 strains were found in 73.5% CRF01_AE in 13.9% CRF07_BC in 6.2% CRF08_BC in 2.7% subtype C in 1.04% subtype B in 0.9% CRF02_AG in 0.4% and B/C intersubtype recombinant strains in 1.3% of the subjects. Twenty-six (3.8%) were found to harbor drug resistance strains. The rates of resistance to protease inhibitors nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors were 0.4% 1.6% and 2.1% respectively. Though there was no significant difference in TDR rates between 2004 and 2005 (2.9% vs. 4.4%) an increased trend was observed in the rate of high-level drug resistance (0.8% in 2004 vs. 3.0% in 2005 P = 0.0634). CONCLUSIONS: The rate of TDR was relatively low in China as compared with those in developed countries. Surveys among recently HIV-infected subjects should be performed continually to ensure the success of the scale-up antiretroviral treatment.

The partial pol gene was analyzed to determine circulating HIV-1 subtypes and the prevalence of drug resistance among recently infected injecting drug users in the west of China. Phylogenetic and bootscanning analyses showed that all 25 sequences belonged to CRF07_BC. No major drug resistance mutations were found, while the CRF07_BC sequences harbored a few highly prevalent polymorphic positions in both the protease and reverse transcriptase regions. It is notable that D60E, L63P and I93L substitutions, which were more common in HIV-1 isolates from PI-treated than untreated patients, were present in most of the isolates. Compared with subtype B, the CRF07_BC strains had a decreased genetic barrier for the V106M mutation, which is selected by efavirenz and leads to high-level resistance to all present nonnucleoside RT inhibitors. Further studies are needed to determine the impact of genetic features of CRF07-BC on antitretroviral susceptibility and evolution of drug resistance mutations.

Objectives To investigate human immunodeficiency virus (HIV) virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China. Design This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group. Settings Guangxi, China. Methods Demographic, ART, and laboratory data (CD4+ cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis. Results A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6–35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10 (7.0%) experienced virologic failure, and the overall prevalence of HIV drug resistance was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included self-reported missing doses in the past month (compared to not missing doses in the past month, AOR = 0.2, 95% CI: 0.1–0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR = 0.2, 95% CI: 0.1–0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P = 0.002). Conclusion This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is an important of ART education and adherence to intervention for achieving better treatment outcomes.

Dehong prefecture, Yunnan province on China’s southwestern border was the gateway of the country’s AIDS epidemic. Studies on HIV-1 molecular epidemiology will provide key information on virus transmission dynamics and help to inform HIV prevention strategies. HIV-1 infected youths (age 16–25 years) diagnosed in the continuous 3 months in 2009 to 2012 were enrolled. By means of phylogenetic and statistical analyses, It was showed that two thirds (133/205) of youths in Dehong, of which 74.1% were infected sexually, were infected by uncharacterized recombinant HIV-1 strains. Among them about 59.4% (79/131) were unique recombinant forms (URFs) and 40.6% (54/131) formed 11 transmission clusters, termed potential circulating recombinant forms (pCRFs). The emergence of recombinants was statistically significant related with people of low education, residents outside the capital city of Dehong and being Myanmar residents. It was the first report with ongoing HIV-1 recombinant strains in a sexually driven epidemic area in China. Great efforts should be put on reducing multiple risk exposures behavior in local young people, containing the spread of pCRFs to other regions and preventing the URFs from evolving into future CRFs. Collaborative prevention across border is needed to better control the local AIDS epidemic.

Supplemental Digital Content is available in the text, The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1–5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

Inflammation contributes greatly to the pathogenesis of bronchopulmonary dysplasia. In previous studies, we showed that blocking neutrophil influx by treatment with SB265610, a selective CXCR2 antagonist, could partly reduce superoxide accumulation and preserve alveolar development in 60% O(2)-exposed newborn rats. The purpose of this study was to further investigate the role of neutrophils in the formation of reactive oxygen and nitrogen species mediating hyperoxia-impaired lung development. We found that hydroxyl radical formation and lipid peroxidation in rat lungs were significantly increased during 60% O(2) exposure. These increases were attenuated by the administration of SB265610. In addition, SB265610 largely inhibited protein nitration induced by hyperoxia. SB265610 partly prevented the hyperoxia-enhanced bronchoalveolar lavage (BAL) protein content in 60% O(2)-exposed animals. Our results demonstrate that neutrophils have a pivotal role in hydroxyl radical formation, lipid peroxidation and protein nitration. Taken together with our previous studies, the present findings show that blocking neutrophil influx protects alveolar development and improves lung function in part by preventing reactive oxygen/nitrogen species accumulation.

It is known that transmitted drug resistance (TDR) will most likely emerge in regions where antiretroviral therapy (ART) has been widely available for years. However, after a decade of rapid scale-up of ART in China, there are few data regarding TDR among HIV-infected patients prior to initiating first-line ART in China. A prospective, observational cohort study was performed at sentinel sites in five provinces or municipalities. Study participants were recruited at the county- or city-level centers for disease control (CDCs), during routine monitoring visits following referral from diagnosing parties (e.g., hospitals). Each province or municipality recruited 140 patients through sequential sampling throughout the 2011 calendar year. A total of 627 eligible subjects were included in the analysis. the median CD4(+) cell count was 206 cells/ml at the baseline survey. The majority of patients (93.5%) had plasma HIV viral load ≥1,000 copies/ml. Of the 627 patients, 17 (2.7%) had drug resistance mutations for any type of HIV drugs. The prevalence of drug resistance mutations to nonnucleoside reverse transcriptase inhibitor (NNRTI) drugs (8/627, 1.3%) was higher than to nucleoside reverse transcriptase inhibitor (NRTI) drugs (5/627, 0.8%) and protease inhibitor (PI) drugs (4/627, 0.6%). A logistic regression model showed that the only predictive factor was the route of infection through homosexual intercourse, i.e., men who have sex with men (MSM) status. As HIV prevalence is rising rapidly among Chinese MSM, it is essential to continue surveying this risk group and related high-risk populations with low awareness of HIV, and to develop new public health interventions that help to reduce the spread of drug-resistant HIV.

Background 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. Methods 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. Results 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. Conclusions 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.

BackgroundChina's National Free Antiretroviral Treatment Program (NFATP) has significantly scaled up and standardized treatment since 2008. Meanwhile, no study worldwide has examined on a large scale the effects of rapid ART programme scale-up on treatment outcomes in resource-limited settings.MethodsWe used China's national HIV drug resistance (HIVDR) surveillance database to determine virological failure, acquired drug resistance and poor adherence rates after 12–15 months of first-line ART. A total of 2252 patients were examined, with 1431 patients having initiated ART before 2008 and 821 since 2008.FindingsSince 2008, virological failure at 12–15 months of treatment improved from 26.6% to 12.1%, and HIVDR rates also significantly decreased from 15.4% to 5.4%. However, these successes are strongly associated with the standardized use of lamivudine-based regimens in place of didanosine-based regimens. Patients who initiated lamivudine-based regimens before 2008 showed significant improvement in adherence [missed doses adjusted OR (AOR), 0.65; 95% CI, 0.45–0.96], virological failure (AOR, 0.29; 95% CI, 0.22–0.39) and HIVDR outcomes (AOR, 0.29; 95% CI, 0.20–0.42) compared with those who initiated didanosine-based regimens. Meanwhile, among only patients on lamivudine-based regimens, no significant changes were observed between those who initiated before 2008 and those who initiated since 2008.ConclusionsChina's NFATP has been largely successful throughout the scale-up, with an overall reduction in virological failure and HIVDR. However, excluding the effect of lamivudine-based regimens, it remains crucial for the programme to improve patient adherence and quality of care, particularly in key vulnerable populations such as those infected through injecting drug or blood routes.