Emergence of HIV-1 drug resistance mutations among children and adolescents undergoing prolonged antiretroviral therapy in Guangxi.

OBJECTIVE: Antiretroviral therapy (ART) has been implemented in Guangxi for a long time, and there are no reports of HIV drug resistance mutation (DRM) among children and adolescents experiencing virologic failure after ART. This study aimed to analyse HIV DRM prevalence, patterns, and influencing factors among children and adolescents experiencing virologic failure after ART in Guangxi. METHODS: We collected samples from a total of 491 HIV-infected individuals under 18 years old experiencing virologic failure after ART from 14 cities in Guangxi. Sequencing and DRM analysis were performed based on pol region. Multivariate logistic regression was employed to analysis the influencing factors of DRM. RESULTS: Among these patients, 396 cases were successfully sequenced. Of all, 52.53% exhibited HIV DRM, including NNRTI (48.48%), NRTI (34.85%) and PI (1.01%). NRTI and NNRTI dual-class resistance was prevalent (30.3%). M184V/I and K103N mutations were the common mutations in NRTI and NNRTI, respectively. Male sex (aOR = 2.1, 95% CI: 1.26-3.50), CRF01_AE subtype (OR = 2.50, 95% CI: 1.02-5.88), the primary regimen 3TC+AZT+NVP (OR = 10.00, 95% CI: 5.00-25.00), low pretreatment CD4+ T lymphocytes (<200 cells/mm³) (OR = 1.85, 95% CI: 1.00-3.45), and high viral load (>1000 copies/mL) (OR = 4.90, 95% CI: 1.03-23.39) showed higher risk of DRM. CONCLUSION: HIV DRM is pervasive among children and adolescents experiencing virologic failure in Guangxi. Timely HIV DRM monitoring is crucial to mitigate major mutation accumulation and inform effective treatment strategies.

Drug resistance and influencing factors in HIV-1-infected individuals under antiretroviral therapy in Guangxi, China.

OBJECTIVES: To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi. METHODS: Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV Drug Resistance Database. Logistic regression was employed to identify potential risk factors associated with both HIV drug resistance and mortality. RESULTS: A total of 8963 individuals with pol sequences were included in this study. The overall prevalence of HIV-1 drug resistance (HIVDR) was 42.43% (3808/8963), showing a decrease from 59.62% to 41.40% from 2016 to 2023. Factors such as being aged ≥50 years, male, Han nationality, lower education levels, occupations including workers, peasants and children, AIDS, pre-treatment CD4 T cell counts <200 cells/mm3, infection with CRF01_AE and CRF55_01B subtypes, and ART regimen lamivudine/zidovudine/nevirapine were associated with higher susceptibility to HIVDR. The common mutations were M184V (17.38%) and K103N (22.14%). Additionally, the prevalence of M184V, S68G, M41L and G190A were different between the Han and Zhuang populations. Factors including age, gender, ethnicity, education level, occupation, infectious route, clinical stage, viral load, subtype, ART regimen and HIVDR showed significant associations with mortality. CONCLUSIONS: The factors contributing to drug resistance in the HIV-1 ART individuals in Guangxi appear to be notably intricate. Continuous reinforcement of drug resistance surveillance is imperative, accompanied by the optimization of ART regimens to mitigate virological failures effectively.

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.

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.

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.

[Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi].

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

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.

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.

Disparity of HIV-1 Pretreatment Drug Resistance in Men Who Have Sex With Men and the Heterosexual Population in Guangxi, China.

Background: The prevalence of human immunodeficiency type 1 (HIV-1) pretreatment drug resistance (PDR) in men who have sex with men (MSM) in Guangxi remains unclear, and its effect on antiretroviral therapy (ART) needs to be further studied. Methods: Individuals newly diagnosed with HIV in Guangxi from 2016 to 2020, which mainly included MSM and the heterosexual (HES) population, were recruited in this study. Pol sequences were sequenced to analyze PDR and construct a genetic network. The risk factors for PDR and the effect on ART were respectively analyzed. Results: The PDR of MSM in Guangxi was 4.7% (34/716), consisting of nonnucleoside reverse transcriptase inhibitors (3.5%), protease inhibitors (0.8%), integrase strand transfer inhibitors (0.7%), and nucleoside reverse transcriptase inhibitors (0.4%), and lower than that of HES (9.3% [77/827]). The subtype was associated with PDR, and MSM was lower than HES (CRF01_AE: 3.0% vs 8.0%; CRF07_BC: 4.1% vs 7.2%). CRF55_01B (adjusted odds ratio [aOR], 3.35) was a risk factor for PDR in MSM, while CRF08_BC (aOR, 2.34) and older (aOR, 2.75) were risk factors for PDR in HES. Six of 18 (33.3%) PDR of MSM in the network connected to each other, lower than that of HES (61.1% [22/36]). CRF55_01B (aOR, 5.69) was a risk factor for PDR transmission in MSM, while CRF08_BC (aOR, 4.08) was a risk factor in HES. Pretreatment CD4+ T-cell count, age, infection route, and subtype were associated with recovery of CD4+ count and suppression of viral load. Conclusions: The prevalence of PDR was different between MSM and HES, which may be associated with subtype. Thus, the monitoring of subtype and PDR should be strengthened.

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.

Distinct Rates and Transmission Patterns of Major HIV-1 Subtypes among Men who Have Sex with Men in Guangxi, China.

The diversity and transmission patterns of major HIV-1 subtypes among MSM population in Guangxi remains unknown. Understanding the characteristics is crucial for effective intervention strategies. Between 2016 and 2021, we recruited individuals newly diagnosed with HIV-1 from MSM population in Guangxi. HIV-1 pol region was amplified and sequenced, and constructed molecular network, assessed clustering rate, cluster growth rate, spatial clustering, and calculating the basic reproductive number (R0) based on sequences data. We identified 16 prevalent HIV-1 subtypes among Guangxi MSM, with CRF07_BC (53.1%), CRF01_AE (26.23%), and CRF55_01B (12.96%) predominating. In the network, 618 individuals (66.17%) formed 59 clusters. Factors contributing to clustering included age < 30 years (AOR = 1.35), unmarried status (AOR = 1.67), CRF07_BC subtype (AOR = 3.21), and high viral load (AOR = 1.43). CRF07_BC had a higher likelihood of forming larger clusters and having higher degree than CRF01_AE and CRF55_01B. Notably, CRF07_BC has higher cluster growth rate and higher basic reproductive number than CRF01_AE and CRF55_01B. Our findings underscore CRF07_BC as a prominent driver of HIV-1 spread among Guangxi's MSM population, highlighting the viability of targeted interventions directed at specific subtypes and super clusters to control HIV-1 transmission within this population.

Genetic network analysis of human immunodeficiency virus sexual transmission in rural Southwest China after the expansion of antiretroviral therapy: A population-based study.

Background: This 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 methods: This 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. Results: Of 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 <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43-0.82] and 65% [AOR: 0.35, 95% CI: 0.24-0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission. Conclusion: This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time.

The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. All 24 Env-pseudotyped viruses were resistant to bNAbs 2G12, PGT121, and PGT135. The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.

A comprehensive cross-sectional survey to identify barriers and facilitators of cervical cancer screening in women with HIV in Guangxi, China.

BACKGROUND: Co-infection with HIV is a strong risk factor for cervical cancer development. It is unknown whether women with HIV in Guangxi, China are utilizing currently available cervical cancer screening services, what barriers they face, and if they are aware of their increased risk of developing cervical cancer. METHODS: Using a cross-sectional design, we administered a survey to women with HIV aged 21-65 years from August to October 2019 in Guangxi, China. A 100-item survey was designed in English and translated into Chinese. We assessed knowledge, attitudes, and beliefs about cervical cancer and cervical cancer screening, identified potential barriers and facilitators of cervical cancer screening programs for women with HIV, and assessed potential risk factors for cervical cancer. RESULTS: A total of 101 participants completed the survey. The median age of participants was 38 years (IQR 34.5-44 years). Forty-seven percent of the women had been screened for cervical cancer at least once. The mean score was 5.6 out of 9 (95% CI 5.3-6.0) on the knowledge about cervical cancer and screening and 6.3 out of 10 (95% CI 5.9-6.6) for cervical cancer risk factors, respectively. Facilitators of participating in cervical cancer screening included trust and openness to healthcare workers having conversations about female health concerns. Barriers identified in our study included knowledge gaps in cervical cancer risk awareness and cervical cancer screening awareness, including the lack of knowledge of available cervical cancer screening services. Women with HIV in Guangxi are under-screened for cervical cancer. CONCLUSION: When designing tailored cervical cancer screening programs for women with HIV in Guangxi, educational programs to address existing knowledge gaps will be needed to increase screening uptake in this high-risk population.

Nonstudent Young Men Put Students at High Risk of HIV Acquisition in Guangxi, China: A Phylogenetic Analysis of Surveillance Data.

BACKGROUND: We sought to identify students and their sexual partners in a molecular transmission network. METHODS: We obtained 5996 HIV protease and reverse transcriptase gene sequences in Guangxi (165 from students and 5831 from the general populations) and the relevant demographic data. We constructed a molecular transmission network and introduced a permutation test to assess the robust genetic linkages. We calculated the centrality measures to describe the transmission patterns in clusters. RESULTS: At the network level, 68 (41.2%) students fell within the network across 43 (8.1%) clusters. Of 141 genetic linkages between students and their partners, only 25 (17.7%) occurred within students. Students were more likely than random permutations to link to other students (odds ratio [OR], 7.2; P < .001), private company employees aged 16-24 years (OR, 3.3; P = .01), private company or government employees aged 25-49 years (OR, 1.7; P = .03), and freelancers or unemployed individuals aged 16-24 years (OR, 5.0; P < .001). At the cluster level, the median age of nonstudents directly linked to students (interquartile range) was 25 (22-30) years, and 80.3% of them had a high school or higher education background. Compared with students, they showed a significantly higher median degree (4.0 vs 2.0; P < .001) but an equivalent median Eigenvector Centrality (0.83 vs 0.81; P = .60). CONCLUSIONS: The tendency of genetic linkage between students and nonstudent young men and their important position in the HIV transmission network emphasizes the urgent need for 2-pronged public health interventions based on both school and society.

Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014-18.

OBJECTIVES: To evaluate the prevalence and characteristics of doravirine resistance and cross-resistance in patients who failed first-line ART in China. METHODS: From 2014 to 2108, 4132 patients from five provinces were tested for drug resistance by genotypic resistance testing. Drug resistance mutations were assessed using the Stanford HIVdb algorithm Version 9.0. Sequences classified as having low-level, intermediate and high-level resistance were defined as having drug resistance. RESULTS: Overall, the prevalence of doravirine and other NNRTIs cross-resistance was 69.5%, with intermediate and high-level resistance accounting for 56.4%. Doravirine resistance highly correlated with efavirenz (r = 0.720) and nevirapine (r = 0.721) resistance and moderately correlated with etravirine (r = 0.637) and rilpivirine (r = 0.692) resistance. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). There were significant differences between genotypes and provinces. Compared with CRF01_AE, CRF07_BC (OR = 0.595, 95% CI = 0.546-0.648) and CRF08_BC (OR = 0.467, 95% CI = 0.407-0.536) were associated with lower risks of doravirine resistance. Conversely, genotype A (OR = 3.003, 95% CI = 1.806-4.991) and genotype B (OR = 1.250, 95% CI = 1.021-1.531) were associated with higher risks of doravirine resistance. The risk of doravirine resistance was significantly lower in Xinjiang compared with other provinces. CONCLUSIONS: In China, the prevalence of doravirine cross-resistance among patients who have failed first-line ART is high. Therefore, doravirine should not be used blindly without genotypic resistance testing and is not recommended for people who have failed first-line NNRTI-based ART.

Immune reconstruction effectiveness of combination antiretroviral therapy for HIV-1 CRF01_AE cluster 1 and 2 infected individuals.

There are great disparities of the results in immune reconstruction (IR) of the HIV-1 infected patients during combined antiretroviral therapy (cART), due to both host polymorphisms and viral genetic subtypes. Identifying these factors and elucidating their impact on the IR could help to improve the efficacy. To study the factors influencing the IR, we conducted a 15-year retrospective cohort study of HIV-1 infected individuals under cART. The trend of CD4+ count changes was evaluated by the generalized estimating equations. Cox proportional model and propensity score matching were used to identify variables that affect the possibility of achieving IR. The tropism characteristics of virus were compared using the coreceptor binding model. In addition to baseline CD4+ counts and age implications, CRF01_AE cluster 1 was associated with a poorer probability of achieving IR than infection with cluster 2 (aHR, 1.39; 95%CI, 1.02-1.90) and other subtypes (aHR, 1.83; 95%CI, 1.31-2.56). The mean time from cART initiation to achieve IR was much longer in patients infected by CRF01_AE cluster 1 than other subtypes/sub-clusters (P < 0.001). In-depth analysis indicated that a higher proportion of CXCR4 viruses were found in CRF01_AE clusters 1 and 2 (P < 0.05), and showed tendency to favour CXCR4 binding to V3 signatures. This study indicated the immune restoration impairment found in patients were associated with HIV-1 CRF01_AE cluster 1, which was attributed to the high proportion of CXCR4-tropic viruses. To improve the effectiveness of cART, more efforts should be made in the early identification of HIV-1 subtype/sub-cluster and monitoring of virus phenotypes.

Impacts of HIV-1 Subtype Diversity on Long-Term Clinical Outcomes in Antiretroviral Therapy in Guangxi, China.

BACKGROUND: Comprehensively estimating the impacts of HIV-1 subtype diversity on long-term clinical outcomes during antiretroviral therapy (ART) can help inform program recommendations. METHODS: The HIV-1 sequence data and clinical records of 5950 patients from all 14 prefectures in Guangxi, China, during 2008-2020 were included. Evolutional trends of CD4+ T-lymphocyte count and viral load were explored, and the effects of HIV-1 subtypes on clinical outcomes were estimated by the Cox proportional hazards model. The polymorphisms involved in drug resistance mutation were analyzed. RESULTS: Compared with patients with CRF07_BC, patients with CRF01_AE and CRF08_BC showed poor immunologic and virologic responses to antiretroviral therapy. Although the median expected time from ART initiation to virologic suppression for all patients was approximately 12 months, patients with CRF01_AE and CRF08_BC had a long time to achieve immune recovery and a short time to occur immunologic failure, compared with patients with CRF07_BC. Adjusted analysis showed that both CRF01_AE and CRF08_BC were the negative factors in immune recovery and long-term mortality. In addition, CRF08_BC was a negative factor in virologic suppression and a risk factor of virologic failure. This poor virologic response might result from the high prevalence of drug resistance mutation in CRF08_BC. CONCLUSIONS: Compared with patients with CRF07_BC, patients with CRF01_AE could benefit more from immediate ART, and patients with CRF08_BC are more suitable for PI-based regimens. These data emphasize the importance of routine HIV-1 genotyping before ART, immediate ART, and personalized ART regimens to improve the prognosis for patients undergoing ART.