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BackgroundLong-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive.MethodsTo investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells.ResultsThe combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs.ConclusionIn summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.

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.

HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.

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.

AbstractBackground Hepatitis B virus (HBV) and syphilis have been the most common co-infections that hinder treatment outcomes and increase early mortality among people living with human immunodeficiency virus (PLHIV). In this study, we aimed to determine the burden of HBV and syphilis co-infections and its impact on treatment outcomes among PLHIV in Ethiopia.Methods We used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), which was a household-based national survey in 2017/2018. Human immunodeficiency virus (HIV) testing was done among 19,136 participants using the national testing algorithm and 662 participants (3.50%) were HIV positives who were further tested for viral hepatitis and syphilis co-infections using HBV surface antigen and Chembio DPP syphilis assay, respectively. Viral load, CD4 count and high-sensitivity C-reactive protein (hsCRP) were done to measure HIV treatment outcomes. Descriptive statistics were used to determine the burden of co-infections and a logistic regression model to evaluate the determinants of co-infections using STATA V17.0.Results Overall prevalence of HBV and syphilis co-infection was 5.5% and 2.2%, respectively. HBV and syphilis (double co-infection) was 5.9%. The highest prevalence of HBV co-infection was observed among 10–19 years age group (12.9%) and male participants (7.44%) while the highest syphilis co-infection was among people aged ≥50 years (3.5%) followed by age groups 40–49 (3.3%) and 10–19 years (3.2%). Syphilis co-infection was higher among males (5.2%) compared to females (1.1%). After adjusted regression analysis, HBV co-infected PLHIV had higher odds of virologic failure (AOR (95% confidence interval (CI)) = 6.3 (4.2–14.3)), immunosuppression (CD4 count < 500 cells/mm3) (AOR (95%CI) = 2.1(1.3–4.9)) and inflammation (hsCRP >10 mg/dL) (AOR (95%CI) = 9.2(4.3–14.6)). Immunosuppression was also significantly higher among syphilis co-infected PLHIV (AOR (95%CI) = 3.4 (1.3–5.2)).Conclusions Burden of HBV and syphilis co-infections is high particularly among male and adolescent PLHIV and these co-infections hinder virologic and immunologic outcome in Ethiopia. Hence, the program shall enhance HBV and syphilis testing and treatment.

ABSTRACTHIV-1 infection is mediated by a viral envelope subsequently binding to CD4 receptor and two main coreceptors, CCR5 (R5) for primary infection and CXCR4 (X4) in chronic infection. Switching from R5 to X4 tropism in HIV-1 infection is associated with increased viral pathogenesis and disease progression. The coreceptor switching is mainly due to variations in the V3 loop, while the mechanism needs to be further elucidated. We systematically studied the determinant for HIV-1 coreceptor switching by substitution of the genes from one R5 and one X4 pseudoviruses. The study results in successfully constructing two panels of chimeric viruses of R5 to X4 forward and X4 to R5 reverse switching. The determinants for tropism switching are the combined substitution of the V3 loop and C4 region of the HIV-1 envelope. The possible mechanism of the tropism switching includes two components, the V3 loop to enable the viral envelope binding to the newly switched coreceptor and the C4 region, to compensate for the loss of fitness caused by deleterious V3 loop mutations to maintain the overall viral viability. The combined C4 and V3 substitution showed at least an eightfold increase in replication activity compared with the pseudovirus with only V3 loop substitution. The site-directed mutations of N425R and S440-I442 with charged amino acids could especially increase viral activity. This study could facilitate HIV-1 phenotype surveillance and select right entry inhibitor, CCR5 or CXCR4 antagonists, for antiviral therapy.

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 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

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: Objectives: The aim of this study was to evaluate HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia. Methods: 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 of

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 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

Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 disease progression and drug resistance mutation among children on first-line antiretroviral therapy in Ethiopia. Method: A longitudinal study was conducted among 551 HIV-positive children (pol gene region using in-house assay validated at the Chinese Center for Disease Control and Prevention, and the Stanford HIVDB v9.0 algorithm was used for identification of drug resistance mutations. The Kaplan–Meier analysis and Cox proportional hazards regression model were used to estimate the rate and predictors of disease progression, respectively. Results: The disease progression rate was 6.3 per 100 person-years-observation (95% CI = 4.21–8.53). Overall immunosuppression (CD4 count < 200 cells/mm3) during the 12-year follow-up was 11.3% (95% CI = 7.5–15.1). Immunosuppression was significantly increased as of the mean duration of 10.5 (95% CI = 10.1–10.8) years (38.2%) to 67.8% at 12 years (p < 0.001). Overall, 14.5% had resistance to at least one drug, and 6.2% had multi-drug resistance. A resistance of 67.8% was observed among children with VF. Resistance to non-nucleotide reverse transcriptase inhibitors (NNRTI) and nucleotide reverse transcriptase inhibitors (NRTI) drugs were 11.4% and 10.1%, respectively. Mutations responsible for NRTI resistance were M184V (30.1%), K65R (12.1%), and D67N (5.6%). Moreover, NNRTI-associated mutations were K103N (14.8%), Y181C (11.8%), and G190A (7.7%). Children who had a history of opportunistic infection [AHR (95% CI) = 3.4 (1.8–6.2)], vitamin D < 20 ng/mL [AHR (95% CI) = 4.5 (2.1–9.9)], drug resistance [AHR (95% CI) = 2.2 (1.4–3.6)], and VF [AHR (95% CI) = 2.82 (1.21, 3.53)] had a higher hazard of disease progression; whereas, being orphan [AOR (95% CI) = 1.8 (1.2–3.1)], history of drug substitution [(AOR (95% CI) = 4.8 (2.1–6.5), hemoglobin < 12 mg/dL [AOR (95% CI) = 1.2 (1.1–2.1)] had higher odds of developing drug resistance. Conclusions: Immunosuppression was increasing over time and drug resistance was also substantially high. Enhancing routine monitoring of viral load and HIVDR and providing a vitamin-D supplement during clinical management could help improve the immunologic outcome. Limiting HAART substitution is also crucial for children taking HAART in Ethiopia.

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.

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.

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 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

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 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.

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.

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%.

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.

OBJECTIVE: To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment. METHODS: A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance. RESULTS: A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm(3), which increased from 192 cells/mm(3) at baseline (P

BACKGROUND: The polymorphisms involved in drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF_BC, the most prevalent HIV-1 strain in China, have been poorly characterized. RESULTS: To reveal the drug resistance mutations, we compared the gene sequences of pol region of HIV-1 CRF_BC from 631 treatment-naïve and 363 treatment-experienced patients using the selection pressure-based method. We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that eight polymorphic mutations (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) in RT for treatment-experienced patients were identified, while they, except for R135L, were completely absent in those from treatment-naïve patients. The I132L and T139K/R mutants exhibited high-level resistance to DLV and NVP and moderate resistance to TMC-125 and EFV, while the K101Q and H221Y mutants exhibited an increased resistance to all four NNRTIs tested. The W88C, R135L, and L228R may be RTI-induced adaptive mutations. Y181C+K101Q mutant showed a 2.5-, 4.4-, and 4.7-fold higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant, while Y181C+H221Y or K103N+H221Y mutants had significantly higher resistance to all four NNRTIs than Y181C or K103N mutants. K103N+T139K and G190A+T139K mutant induce higher resistance (2.0∼14.2-fold and 1.5∼7.2-fold, respectively) to all four NNRTIs than K103N or G190A alone mutation. CONCLUSIONS: I132L and T139K/R are rare but critical mutations associated with NNRTI-resistance for some NNRTIs. K101Q, H221Y and T139K can enhance K103N/Y181C/G190A-assocated NNRTI-resistance. Monitoring these mutations will provide useful information for rational design of the NNRTI-based antiretroviral regimen for HIV-1 CRF_BC-infected patients.

BACKGROUND: A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale. METHODS: HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. RESULTS: The overall prevalence of HIV RNA ≥ 1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. CONCLUSIONS: The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.

BACKGROUND: Highly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART. METHODS: Three cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression. RESULTS: 3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6-28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province. CONCLUSIONS: Virologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.