HBV and HCV Co-Infection in Chinese Newly Diagnosed HIV+ Subjects in 2015 and 2023: A Cross-Sectional Study.

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.

Distinct genetic clusters in HIV-1 CRF01_AE-infected patients induced variable degrees of CD4+ T-cell loss.

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

Diagnostic performance evaluation of urine HIV-1 antibody rapid test kits in a real-life routine care setting in China.

OBJECTIVES: To evaluate the diagnostic performance of urine HIV antibody rapid test kits in screening diverse populations and to analyse subjects' willingness regarding reagent types, purchase channels, acceptable prices, and self-testing. DESIGNS: Diagnostic accuracy studies PARTICIPANTS: A total of 2606 valid and eligible samples were collected in the study, including 202 samples from female sex workers (FSWs), 304 persons with injection drug use (IDU), 1000 pregnant women (PW), 100 subjects undergoing voluntary HIV counselling and testing (VCT) and 1000 students in higher education schools or colleges (STUs). Subjects should simultaneously meet the following inclusion criteria: (1) being at least 18 years old and in full civil capacity, (2) signing an informed consent form and (3) providing truthful identifying information to ensure that the subjects and their samples are unique. RESULTS: The sensitivity, specificity and area under the curve (AUC) of the urine HIV-1 antibody rapid test kits were 92.16%, 99.92% and 0.960 (95% CI: 0.952 to 0.968, p<0.001), respectively, among 2606 samples collected during on-site screenings. The kits showed good diagnostic performance in persons with IDU (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001), PW (AUC, 0.999; 95% CI, 0.999 to 1.000, p<0.001) and FSWs (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001). The AUC of the urine reagent kits in subjects undergoing VCT was 0.941 (95% CI: 0.876 to 0.978, p<0.001). The 'acceptable price' had the greatest influence on STUs (Pi=1.000) and PW (Pi=1.000), the 'purchase channel' had the greatest influence on subjects undergoing VCT (Pi=1.000) and persons with IDU (Pi=1.000) and the 'reagent types' had the greatest influence on FSWs (Pi=1.000). CONCLUSIONS: The rapid urine test kits showed good diagnostic validity in practical applications, despite a few cases involving misdiagnosis and underdiagnosis.

Criteria for classification, nomenclature, and reference sequence selection for HIV sub-subtypes of CRF01_AE and CRF07_BC strains in China.

The available knowledge regarding classification, nomenclature, and reference sequence selection for the various sub-subtypes of circulating recombinant forms (CRFs) is inadequate to fulfill the growing demands of research focused on HIV prevention. We analyzed the spread of CRF01_AE and CRF07_BC strains, mainly in China, to complement and update the existing nomenclature and to propose a reference sequence selection criteria for sub-subtypes of CRFs.

Metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease from clinical to pathological characteristics: a multi-center cross-sectional study in real world.

BACKGROUND: The evaluation of patients with fatty liver as defined by metabolic dysfunction-associated fatty liver disease (MAFLD) in the real world remains poorly researched. This study aimed to analyse the clinical and histological features of patients with MAFLD and nonalcoholic fatty liver disease (NAFLD) and to characterize each metabolic subgroup of MAFLD. METHODS: A total of 2563 patients with fatty liver confirmed by ultrasonography and/or magnetic resonance tomography and/or liver biopsy-proven from three hospitals in China were included in the study. Patients were divided into different groups according to diagnostic criteria for MAFLD and NAFLD, and MAFLD into different subgroups. RESULTS: There were 2337 (91.2%) patients fitting the MAFLD criteria, and 2095 (81.7%) fitting the NAFLD criteria. Compared to patients with NAFLD, those with MAFLD were more likely to be male, had more metabolic traits, higher liver enzyme levels, and noninvasive fibrosis scores. Among the patients with liver biopsy, the extent of advanced fibrosis in cases with MAFLD was significantly higher than those with NAFLD, 31.8% versus 5.2% (P < .001); there was no significant difference in advanced fibrosis between obese cases and lean individuals in MAFLD (P > .05); MAFLD complicated with diabetes had significantly higher advanced fibrosis than those without diabetes (43.3% and 17.2%, respectively; P < .001). CONCLUSIONS: Patients with MAFLD have a higher degree of liver fibrosis than NAFLD patients. In addition, diabetic patients should be screened for fatty liver and liver fibrosis degree.

HIV transmission and associated factors under the scale-up of HIV antiretroviral therapy: a population-based longitudinal molecular network study.

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.

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.

Pretreatment HIV Drug Resistance and the Molecular Transmission Network Among HIV-Positive Individuals in China in 2022: Multicenter Observational Study.

BACKGROUND: Emerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings. OBJECTIVE: We aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022. METHODS: This 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. RESULTS: PDR 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. CONCLUSIONS: The 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.

Impact of pretreatment low-abundance HIV-1 drug resistance on virological failure after 1 year of antiretroviral therapy in China.

OBJECTIVES: To assess the impact of pretreatment low-abundance HIV drug-resistant variants (LA-DRVs) on virological outcomes among ART-naive HIV-1-infected Chinese people who initiated ART. METHODS: A nested case-control study was conducted among HIV-1-infected individuals who had pretreatment drug resistance (PDR) genotypic results. Cases were defined as individuals with virological failure (HIV-1 RNA viral load ≥1000 copies/mL) after 1 year of ART, and controls were individuals from the same cohort whose viral load was less than 1000 copies/mL. Next-generation sequencing was used to identify low-abundance PDR mutations at detection thresholds of 10%, 2% and 1%. The mutant load was calculated by multiplying the abundance of HIV-1 drug-resistant variants by the pretreatment viral load. The impact of pretreatment low-abundance mutations on virological failure was estimated in logistic regression models. RESULTS: Participants (43 cases and 100 controls) were included in this study for the analysis. The proportion of participants with PDR was higher in cases than in controls at different detection thresholds (44.2% versus 22.0%, P = 0.007 at 10% threshold; 58.1% versus 31.0%, P = 0.002 at 2% threshold; 90.7% versus 69.0%, P = 0.006 at 1% threshold). Compared with participants without PDR, participants with ≥10% detectable PDR mutations were associated with an increased risk of virological failure (adjusted OR 8.0, 95% CI 2.4-26.3, P = 0.001). Besides this, individuals with pretreatment LA-DRVs (2%-9% abundance range) had 5-fold higher odds of virological failure (adjusted OR 5.0, 95% CI 1.3-19.6, P = 0.021). Furthermore, LA-DRVs at 2%-9% abundance resistant to NRTIs and mutants with abundance of ≥10% resistant to NNRTIs had a 4-fold and 8-fold risk of experiencing virological failure, respectively. It was also found that a mutant load of more than 1000 copies/mL was predictive of virological failure (adjusted OR 7.2, 95% CI 2.5-21.1, P = 0.0003). CONCLUSIONS: Low-abundance PDR mutations ranging from 2% to 9% of abundance can increase the risk of virological failure. Further studies are warranted to define a clinically relevant threshold of LA-DRVs and the role of NRTI LA-DRVs.

The lead time and geographical variations of Baidu Search Index in the early warning of COVID-19.

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

Changes in HIV-1 Subtypes/Sub-Subtypes, and Transmitted Drug Resistance Among ART-Naïve HIV-Infected Individuals - China, 2004-2022.

Introduction: The efficacy of treatment and clinical outcomes may be jeopardized by factors such as transmitted drug resistance (TDR) and the genetic diversity of the human immunodeficiency virus type 1 (HIV-1). This comprehensive study aims to examine the alterations in HIV-1 subtypes or sub-subtypes and TDR among Chinese individuals, who have been diagnosed with HIV infection and are previously untreated with antiretroviral therapy (ART), across the span of 2004 to 2022. Methods: Sequences of the HIV-1 pol gene region were obtained from ART-naïve HIV-positive individuals across 31 provincial-level administrative divisions between 2004 and 2022. To predict susceptibility to 12 antiretroviral drugs, the research utilized the Stanford HIV Drug Resistance Database. The Cochran-Armitage trend test facilitated the analysis of changes in HIV-1 subtype/sub-subtype prevalence and TDR. This analysis was conducted in alignment with the progression of the National Free Antiretroviral Treatment Program's stages between 2004 and 2022. Results: Among the 57,902 ART-naïve individuals infected with HIV, there was a notable decline in the prevalence of CRF01_AE, B, and C from 37.3%, 24.1%, and 1.3% respectively in 2004-2007 to 29.4%, 7.3%, and 0.2% respectively in 2020-2022. Simultaneously, a significant increase was observed in the proportions of CRF07_BC, CRF08_BC, CRF55_01B, other CRFs, and URFs, from 24.1%, 11.5%, 0.1%, 0.4%, and 0.9% respectively in 2004-2007 to 40.8%, 11.5%, 3.8%, 3.7%, and 2.8% respectively in 2020-2022 (all P<0.001 for trend). The prevalence of TDR to overall, non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, and nevirapine also significantly increased from 2.6%, 1.8%, 1.6%, and 1.8% respectively in 2004-2007 to 7.8%, 6.7%, 6.3%, and 6.7% respectively in 2020-2022 (all P<0.001 for trend). However, there were no meaningful changes in the TDR prevalence of nucleoside reverse transcriptase inhibitor and protease inhibitor. Notably, in 2020-2022, the overall TDR prevalence exceeded 15% in Xinjiang. Conclusions: The total prevalence of TDR in China has achieved a moderate level (7.8%) from 2020 to 2022, with NNRTI resistance standing prominently at 6.7%. Consequently, measures to curb TDR are urgently required, particularly among ART-naïve HIV-infected individuals in China.

Studies on HIV/AIDS Among Students: Bibliometric Analysis.

BACKGROUND: In recent years, HIV infection in students has been an ongoing concern worldwide. A large number of articles have been published; however, statistical analysis of the data presented in these publications is lacking. OBJECTIVE: This study aimed to detect and analyze emerging trends and collaborative networks in research on HIV/AIDS among students. METHODS: Research publications on HIV/AIDS among students from 1985 to 2022 were collected from the Web of Science Core Collection. A topic search was used for this study, and articles in English were included. CiteSpace was used to generate visual networks of countries/regions, institutions, references, and keywords. Citation analysis was used to discover milestones in the field and trace the roots of the knowledge base. Keyword analysis was used to detect research hotspots and predict future trends. RESULTS: A total of 2726 publications met the inclusion criteria. Over the past 38 years, the number of publications annually has been on the rise overall. The United States had the highest number of publications (n=1303) and the highest centrality (0.91). The University of California system was the core institution. The main target population of studies on HIV/AIDS among students were medical and university students. These studies focused on students' knowledge, attitudes, risk behaviors, and education about HIV/AIDS. The recent bursting keywords (gay, sexual health, adherence, barriers, mental health, HIV testing, stigma, and antiretroviral therapy) revealed research trends and public interest on this topic. CONCLUSIONS: This study identified countries/regions and institutions contributing to the research area of HIV/AIDS among students and revealed research hotspots and emerging trends. The field of research on HIV/AIDS among students was growing rapidly. The United States was at the center, and the University of California system was the core institution. However, academic collaboration should be strengthened. Future research may focus on exploring gay students, sexual health, adherence, barriers, mental health, HIV testing, stigma, and antiretroviral therapy.

Modelling the impact of treatment adherence on the transmission of HIV drug resistance.

INTRODUCTION: A lower adherence rate (percentage of individuals taking drugs as prescribed) to ART may increase the risk of emergence and transmission of HIV drug resistance, decrease treatment efficacy, and increase mortality rate. Exploring the impact of ART adherence on the transmission of drug resistance could provide insights in controlling the HIV epidemic. METHODS: We proposed a dynamic transmission model incorporating the CD4 cell count-dependent rates of diagnosis, treatment and adherence with transmitted drug resistance (TDR) and acquired drug resistance. This model was calibrated and validated by 2008-2018 HIV/AIDS surveillance data and prevalence of TDR among newly diagnosed treatment-naive individuals from Guangxi, China, respectively. We aimed to identify the impact of adherence on drug resistance and deaths during expanding ART. RESULTS: In the base case (ART at 90% adherence and 79% coverage), we projected the cumulative total new infections, new drug-resistant infections, and HIV-related deaths between 2022 and 2050 would be 420 539, 34 751 and 321 671. Increasing coverage to 95% would reduce the above total new infections (deaths) by 18.85% (15.75%). Reducing adherence to below 57.08% (40.84%) would offset these benefits of increasing coverage to 95% in reducing infections (deaths). Every 10% decrease in adherence would need 5.07% (3.62%) increase in coverage to avoid an increase in infections (deaths). Increasing coverage to 95% with 90% (80%) adherence would increase the above drug-resistant infections by 11.66% (32.98%). CONCLUSIONS: A decrease in adherence might offset the benefits of ART expansion and exacerbate the transmission of drug resistance. Ensuring treated patients' adherence might be as important as expanding ART to untreated individuals.

Behavioral and emotional difficulties and HIV treatment outcomes among HIV-infected children in rural southwestern China.

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

Neutralization Sensitivity and Evolution of Virus in a Chronic HIV-1 Clade B Infected Patient with Neutralizing Activity against Membrane-Proximal External Region.

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

Inferring potential non-disclosed men who have sex with men among self-reported heterosexual men with HIV in Southwest China: A genetic network study.

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

The impact of attrition on the transmission of HIV and drug resistance.

BACKGROUND: Attrition due to loss to follow-up or termination of antiretroviral therapy (ART) among HIV-infected patients in care may increase the risk of emergence and transmission of drug resistance (TDR), diminish benefit of treatment, and increase morbidity and mortality. Understanding the impact of attrition on the epidemic is essential to provide interventions for improving retention in care. METHODS: We developed a comprehensive HIV transmission dynamics model by considering CD4 + cell count dependent diagnosis, treatment, and attrition involving TDR and acquired drug resistance. The model was calibrated by 11 groups HIV/AIDS surveillance data during 2008-2018 from Guangxi, China, and validated by the prevalence of TDR among diagnosed treatment-naive individuals. We aimed to investigate how attrition would affect the transmission of HIV and drug-resistance when expanding ART. RESULTS: In the base case with CD4 + cell count dependent per capita attrition rates 0.025∼0.15 and treatment rates 0.23∼0.42, we projected cumulative total new infections, new drug-resistant infections, and HIV-related deaths over 2022-2030 would be 145 391, 7637, and 51 965, respectively. Increasing treatment rates by 0.1∼0.2 can decrease the above total new infections (deaths) by 1.63∼2.93% (3.52∼6.16%). However, even 0.0114∼0.0220 (0.0352∼0.0695) increase in attrition rates would offset this benefit of decreasing infections (deaths). Increasing treatment rates (attrition rates) by 0.05∼0.1 would increase the above drug-resistant infections by 0.16∼0.30% (22.18∼41.15%). CONCLUSION: A minor increase in attrition can offset the benefit of treatment expansion and increase the transmission of HIV drug resistance. Reducing attrition rates for patients already in treatment may be as important as expanding treatment for untreated patients.

HIV Epidemiology, Care, and Treatment Outcomes Among Student and Nonstudent Youths Living With HIV in Southwest China Between 1996 and 2019: Historical Cohort Study.

BACKGROUND: Nearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes. OBJECTIVE: This study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China. METHODS: We performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases. RESULTS: A total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n=5507, 54%); 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n=614, 70.7% vs n=1447, 15.5%; P<.001), while nonstudent cases were more likely to be infected through heterosexual contact (n=7887, 84.5% vs n=254, 29.3%; P<.001). Moreover, nonstudent cases had a significantly lower CD4 count than student cases at the time of HIV diagnosis (332 vs 362 cells/µL; P<.001). Nonstudents also had a delayed antiretroviral therapy (ART) initiation compared to students (93 days vs 22 days; P<.001). Furthermore, the mortality rate of 0.4 and 1.0 deaths per 100 person-years were recorded for student and nonstudent youths with HIV, respectively. Overall, the mortality risk in nonstudent cases was 2.3 times that of student cases (adjusted hazard ratio [AHR] 2.3, 95% CI 1.2-4.2; P=.008). The virologic failure rate was 2.3 and 2.6 per 100 person-years among student and nonstudent youths living with HIV, respectively. Nonstudent cases had double the risk of virologic failure compared to student cases (AHR 1.9, 95% CI 1.3-2.6; P<.001). CONCLUSIONS: Nonstudent youths living with HIV might face a low CD4 count at the time of HIV diagnosis, delayed ART initiation, and increased risk of death and virologic failure. Thus, HIV prevention and interventions should target youths who dropped out of school early to encourage safe sex and HIV screening, remove barriers to HIV care, and promote early ART initiation to curb the HIV epidemic among youths.

Virologic failure and all-cause mortality among older people living with HIV/AIDS in South China.

This retrospective cohort study investigated older people living with HIV/AIDS (PLWHA) characteristics, HIV care, and treatment outcomes among all cases between 1996 and 2019 in Guangxi, China. Secondary data were extracted from two national surveillance databases. Older (≥50 years old) and younger (18-49 years old) PLWHA were compared regarding demographic and behavioral characteristics, HIV care, virologic failure, and all-cause mortality. Older PLWHA accounted for 41.6% of all HIV cases (N = 144,952) between 1996 and 2019. The proportion of older cases increased from 10.4% to 64.8% for men and from 2.4% to 66.7% for women between 2002 and 2019. Heterosexual contact accounted for 96.0% of older adults. Moreover, older PLWHA had a lower median CD4 count at the HIV diagnosis (193 vs. 212 cells/µL, p < 0.0001) and were less likely to receive antiretroviral therapy (ART) than younger adults (72.1% vs. 86.1%, p < 0.001). The all-cause mortality risk of older PLWHA was 2.87 times of younger adults [adjusted hazard ratio (AHR) 2.87; 95% confidence interval (CI) 2.76-2.98]. In addition, older PLWHA reported an 18% increase in odds for virologic failure than younger adults (AOR 1.18; 95% CI 1.08-1.30). Therefore, enhanced HIV prevention and care are urgently needed in older people.