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.

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.

[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.

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.

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.

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.

HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China.

BACKGROUND: The widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi. METHODS: We enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR. RESULTS: In total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23-4.71), and CRF08_BC subtype (aOR = 2.03, 95% CI: 1.13-3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08_BC subtype may be a risk of the transmission of TDR. CONCLUSIONS: Our findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.

Patterns and risk of HIV-1 transmission network among men who have sex with men in Guangxi, China.

The prevalence of HIV-1 in Guangxi is very high, and the rate of HIV-1 infection among men who have sex with men (MSM) has been increasing. Therefore, it is necessary to explore the patterns and risk factors of HIV transmission in Guangxi. For this purpose, individuals diagnosed with HIV-1 during 2013-2018 in Guangxi were recruited. Phylogenetic relationship, transmission clusters, and genotypic drug resistance analyses were performed based on HIV-1 pol sequences. Related factors were analysed to assess for their association with HIV-1 transmission. CRF07_BC (50.4%) and CRF01_AE (33.4%) were found to be the predominant subtypes. The analysed 1633 sequences (50.15%, Guangxi; 49.85%, other provinces) were segregated into 80 clusters (size per cluster, 2-704). We found that 75.3% of the individuals were in three clusters (size Ëƒ 100), and 73.8% were high-risk spreaders (links ≥ 4). Infection time, marital status, and subtype were significantly associated with HIV-1 transmission. Additionally, 80.2% of recent infections were linked to long-term infections, and 46.2% were linked to other provinces. A low level of transmitted drug resistance was detected (4.8%). Our findings indicated superclusters and high-risk HIV-1 spreaders among the MSM in Guangxi. Effective strategies blocking the route of transmission should be developed.

Author Correction: HIV-1 Transmissions Among Recently Infected Individuals in Southwest China are Predominantly Derived from Circulating Local Strains.

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HIV-1 Transmissions Among Recently Infected Individuals in Southwest China are Predominantly Derived from Circulating Local Strains.

Although the Guangxi region accounts for 10% of all HIV-1 cases new reported in 2011 in China, the sources of the transmitted HIV-1 strains are virtually unknown. To determine the extent to which recent HIV infections were derived from already circulating local strains as opposed to recently introduced strains, we performed a cross-sectional molecular epidemiological investigation of recent infections across Guangxi during 2012-2013. HIV-1 nucleotide sequences were amplified and sequenced. Phylogenetic analyses of pol gene regions were used to determine HIV-1 transmission source strains. Based on 229 sequences generated, the subtype/CRF distribution was as follows: CRF01_AE (61.1%), CRF07_BC (18.8%), CRF08_BC (16.6%), CRF55_01B (3.1%), and subtype B' (0.4%). In total, 213 of 229 (93.0%) sequenced transmission strains were derived from already-circulating local strains. Multivariate logistic regression analysis showed that only an age of 18-25 years was significantly associated with transmission from outside Guangxi (compared to >25 years, AOR: 5.15, 95% CI: 1.18-22.48, p < 0.01). This is the first study to use a Bayesian discrete phylogeographic approach to analyze transmission source strains in China. Our results provide useful data for designing evidence-based prevention strategies and methods for combating the rapid spread of sexually transmitted HIV in Guangxi.

Screening for acute HIV infections and estimating HIV incidence among female sex workers from low-grade venues in Guangxi, China.

BACKGROUND: Guangxi has become one of the provinces with the most severe HIV-1 epidemic in China, where heterosexual contact is the dominant transmission route. However, data of acute HIV infections and HIV incidence among female sex workers (FSWs) from low-grade venues are scant. METHODS: A cross-sectional survey was performed among FSWs from low-grade venues in Guangxi. HIV antibody screening was performed by rapid testing (RT). HIV antibody-negative specimens were screened by pooled nucleic acid amplification testing (NAAT) for acute HIV infections. HIV antibody-positive specimens were further analyzed by Western blot (WB), followed by an HIV-1 BED capture enzyme immunoassay (BED-CEIA) to identify the recent infections. HIV-1 incidence was estimated by the data of pooled NAAT and BED-CEIA, respectively. RESULTS: A total of 7936 FSWs were recruited and answered the questionnaires. We successfully collected the blood samples from 6469 (81.5%) participants, of which 139 (2.1%) were HIV antibody-positive and 6330 (97.9%) were HIV antibody-negative by RT. With pooled NAAT, 7 cases were found to be HIV RNA positive, representing an additional 5.0% of HIV-infected persons and an estimated HIV incidence of 1.45 (95% CI: 1.17-1.76) per 100 person years. There were 137 positive and 2 indeterminate by WB, of which 124 (90.5%) positive specimens were subjected to BED-CEIA testing identifying 28 recent infections. The HIV incidence determined by BED-CEIA testing was 1.04 (95% CI: 0.65-1.43) per 100 person years. The overall prevalence of HIV among FSWs from low-grade venues in Guangxi was 2.2% (95% CI: 1.9-2.6). CONCLUSIONS: We found that the addition of HIV RNA screening to routine HIV antibody testing significantly improved the detection of HIV infection among FSWs from low-grade venues in Guangxi. Our findings also provided the useful baseline data of HIV incidence among this population for targeting local HIV prevention, intervention, monitoring and treatment.

[The role of RNA pooling technique in the diagnosis of acute HIV infection and the estimation on HIV incidence among low-grade-venues female sex workers].

OBJECTIVE: To examine the feasibility of RNA pooling technique in the diagnosis on acute HIV infection among female sex workers (FSWs) working at the low-grade venues. METHODS: Plasma samples from the low-grade-venue FSWs in Guangxi, in 2011 were tested for HIV antibody using the rapid testing method. All samples which were HIV antibody negative in the rapid testing were tested for HIV RNA with RNA pooling technique. FSWs who showed HIV RNA positive were tested for HIV antibody by Western blot method in 3 months. The HIV incidence in the low-grade venue FSWs was counted under the estimation formula. RESULTS: There were 6 469 cases of FSWs who were recruited in this study. Through rapid testing, results showed that HIV antibody was positive in 139 cases, with the positive rate as 2.15%. 6 330 FSWs with HIV antibody negative were tested by HIV RNA pooling method, with 7 of them showing HIV RNA positive, in which 6 cases showed HIV-1 antibody seroconversion, thus were diagnosed as acute HIV infection. HIV incidence in low-grade FSWs appeared to be 1.45 per 100 person years (95%CI:1.17-1.76 per 100 person years) in Guangxi. CONCLUSION: Other than regular routine HIV antibody testing, it seemed necessary to adopt the HIV RNA pooling strategy in high-risk groups such as FSWs, so as to early detect the HIV infection and to timely perform the intervention or treatment programs to prevent sexual transmission of HIV.