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.

Impact of HIV-1 genetic diversity on disease progression: a prospective cohort study in Guangxi.

The high proportion of AIDS cases and mortality rates in Guangxi underscores the urgency to investigate the influence of HIV-1 genetic diversity on disease progression in this region. Newly diagnosed HIV-1 patients were enrolled from January 2016 to December 2021, and the follow-up work and detection of CD4+T lymphocytes were carried out every six months until December 2022. Multivariate logistic regression was used to analyze the factors affecting pre-treatment CD4+T lymphocyte counts, while local weighted regression models (LOESS) and generalized estimating equation models (GEE) were conducted to assess factors influencing CD4+T Lymphocyte Recovery. Cox regression analysis was utilized to examine the impact of subtypes on survival risk. Additionally, HIV-1 env sequences were utilized for predicting CXCR4 and CCR5 receptors. The study encompassed 1867 individuals with pol sequences and 281 with env sequences. Our findings indicate that age over 30, divorced/widowed, peasant, heterosexual infection, CRF01_AE, long-term infection, and Pre-treatment Viral load >10000 copies/ml were factors associated with higher risk for pre-treatment CD4+T lymphocyte decline. Specifically, male gender, age over 30, heterosexual infection (HETs), long-term infection, CRF01_AE, and Pre-treatment CD4 T cell counts below 350/µL were identified as risk factors impeding CD4+T lymphocyte recovery. Pre-treatment CD4+T lymphocyte counts and recovery in individuals infected with CRF01_AE were lower compared to CRF07_BC and CRF55_01B. Additionally, CRF01_AE and CRF08_BC subtypes exhibited higher mortality rates than CRF07_BC, CRF55_01B, and other subtypes. Notably, CRF01_AE demonstrated the highest percentage of CXCR4 affinity ratios. This research unveils the intricate influence of HIV-1 gene diversity on CD4+T lymphocyte dynamics and clinical outcomes. It highlights the multifaceted nature of HIV infection in Guangxi, providing novel insights into subtype-specific disease progression among HIV-infected individuals in this region.

Near Full-Length Genomic Characterization of Two Novel HIV Type 1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) from Guangxi, China.

CRF01_AE and CRF07_BC are the two predominant HIV-1 subtypes currently circulating in China. We identified here a novel CCR5-tropic HIV-1 second-generation recombinant form virus found in two individuals, (GX19017 and GX19032), which were isolated from two HIV-1-positive people in Guangxi, southwest China. Phylogenic analyses indicated that these two sequences were all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, with four recombinant breakpoints observed in the pol, vpu/env, and env gene regions, respectively. The recombinant CRF01_AE region was clustered with the previously described CRF01_AE subcluster 2 lineage, which was characterized by the susceptibility to phenotypic transfer. The genome structure is significantly different from other previously reported CRFs and unique recombination forms. The emergence of a series of novel recombinant strains is indicative of the burgeoning complexity of the HIV-1 epidemic among the sexually transmitted population. Meanwhile, it may furnish significant insights into the dynamics and intricacy of the HIV-1 epidemic in China.

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.