1.HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China.
Ping CEN ; Hua Yue LIANG ; Yuan YANG ; Fei ZHANG ; Shi Xiong YANG ; Ju Cong MO ; Yi FENG ; Jie Gang HUANG ; Chuan Yi NING ; Chun Yuan HUANG ; Yao YANG ; Na LIANG ; Bing Yu LIANG ; Li YE ; Hao LIANG
Biomedical and Environmental Sciences 2023;36(5):418-430
		                        		
		                        			OBJECTIVE:
		                        			The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.
		                        		
		                        			METHODS:
		                        			We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.
		                        		
		                        			RESULTS:
		                        			Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.
		                        		
		                        			CONCLUSION
		                        			HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			HIV-1/genetics*
		                        			;
		                        		
		                        			HIV Infections
		                        			;
		                        		
		                        			Drug Users
		                        			;
		                        		
		                        			Phylogeny
		                        			;
		                        		
		                        			Bayes Theorem
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Genotype
		                        			
		                        		
		                        	
2.Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi.
Ning-Ye FANG ; Wen-Cui WEI ; Jian-Jun LI ; Ping CEN ; Xian-Xiang FENG ; Dong YANG ; Kai-Ling TANG ; Shu-Jia LIANG ; Yu-Lan SHAO ; Hua-Xiang LU ; He JIANG ; Qin MENG ; Shuai-Feng LIU ; Qiu-Ying ZHU ; Huan-Huan CHEN ; Guang-Hua LAN ; Shi-Xiong YANG ; Li-Fang ZHOU ; Jing-Lin MO ; Xian-Min GE
Acta Academiae Medicinae Sinicae 2023;45(3):399-404
		                        		
		                        			
		                        			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.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Reverse Transcriptase Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			HIV Infections/drug therapy*
		                        			;
		                        		
		                        			Drug Resistance, Viral/genetics*
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			HIV-1/genetics*
		                        			;
		                        		
		                        			Protease Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			Genotype
		                        			
		                        		
		                        	
3.Laboratory testing strategies for human immunodeficiency virus (HIV) in blood donors.
Lingling ZHANG ; Erxiong LIU ; Jiao DU ; Ya LI ; Yafen WANG ; Shunli GU ; Qunxing AN
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):539-543
		                        		
		                        			
		                        			Objective To propose the blood detection strategies for human immunodeficiency virus (HIV) among blood donors, and provide reference for the detection, early diagnosis and transmission blocking of HIV. Methods A total of 117 987 blood samples from blood donors were screened using the third- and fourth-generation ELISA HIV detection reagents. Western blot analysis was used to verify the reactive results of the third-generation reagent alone, or both the third-generation and fourth-generation reagents. HIV nucleic acid test was carried out for those with negative test results of the third- and fourth-generation reagents. For those with positive results of the fourth-generation reagent only, nucleic acid test followed by a confirmatory test by Western blot analysis was carried out. Results 117 987 blood samples from blood donors were tested by different reagents. Among them, 55 were tested positive by both the third- and fourth-generation HIV detection reagents at the same time, accounting for 0.047% and 54 cases were confirmed HIV-positive by Western blot analysis, and 1 case was indeterminate, then turned positive during follow-up testing. 26 cases were positive by the third-generation reagent test alone, among which 24 cases were negative and 2 were indeterminate by Western blot analysis. The band types were p24 and gp160 respectively detected by Western blot analysis, and were confirmed to be HIV negative in follow-up testing. 31 cases were positive by the fourth-generation HIV reagent alone, among which 29 were negative by nucleic acid test, and 2 were positive according to the nucleic acid test.Western blot analysis was used to verify that the two cases were negative. However, after 2~4 weeks, the results turned positive when the blood sample was retested by Western blot analysis during the follow-up of these two cases. All the specimens that were tested negative by both the third- and fourth-generation HIV reagents were validated negative by HIV nucleic acid test. Conclusion A combined strategy with both third- and fourth-generation HIV detection reagents can play a complementary role in blood screening among blood donors. The application of complementary tests, such as nucleic acid test and Western blot analysis, can further improve the safety of blood supply, thus contributing to the early diagnosis, prevention, transmission and treatment of blood donors potentially infected by HIV.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			HIV Infections/diagnosis*
		                        			;
		                        		
		                        			HIV Antibodies
		                        			;
		                        		
		                        			Blood Donors
		                        			;
		                        		
		                        			HIV-1
		                        			;
		                        		
		                        			Blotting, Western
		                        			;
		                        		
		                        			Nucleic Acids
		                        			
		                        		
		                        	
6.Efficacy and safety profiles of dolutegravir plus lamivudine vs . bictegravir/emtricitabine/tenofovir alafenamide in therapy-naïve adults with HIV-1.
Yinghua WEI ; Jin LI ; Ruhong XU ; Li WEN ; Yiming DENG ; Lixia HE ; Huijun ZHONG ; Yanhao WANG
Chinese Medical Journal 2023;136(22):2677-2685
		                        		
		                        			BACKGROUND:
		                        			Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.
		                        		
		                        			METHODS:
		                        			This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).
		                        		
		                        			RESULTS:
		                        			We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.
		                        		
		                        			CONCLUSIONS
		                        			In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Anti-HIV Agents/therapeutic use*
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Emtricitabine/pharmacology*
		                        			;
		                        		
		                        			HIV Infections/drug therapy*
		                        			;
		                        		
		                        			HIV-1
		                        			;
		                        		
		                        			Lamivudine/pharmacology*
		                        			;
		                        		
		                        			Lipids
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
8.Pretreatment integrase strand transfer inhibitor resistance in Tianjin, China.
Huan XIA ; Zhangwen GE ; Defa ZHANG ; Yue WU ; Ping MA
Chinese Medical Journal 2023;136(22):2735-2737
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			HIV Infections
		                        			;
		                        		
		                        			HIV-1
		                        			;
		                        		
		                        			Integrases
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Drug Resistance, Viral
		                        			;
		                        		
		                        			Mutation
		                        			
		                        		
		                        	
9.HIV-1 DNA levels in peripheral blood mononuclear cells of patients with HIV-related non-Hodgkin's lymphoma.
Zhenyan WANG ; Jingna XUN ; Zichen SONG ; Yinzhong SHEN ; Li LIU ; Jun CHEN ; Tangkai QI ; Jianjun SUN ; Wei SONG ; Yang TANG ; Shuibao XU ; Junyang YANG ; Bihe ZHAO ; Renfang ZHANG
Chinese Medical Journal 2023;136(22):2741-2743
10.Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure.
Shuang LI ; Hu WANG ; Na GUO ; Bin SU ; Olivier LAMBOTTE ; Tong ZHANG
Chinese Medical Journal 2023;136(22):2658-2667
		                        		
		                        			
		                        			Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunotherapy, Adoptive
		                        			;
		                        		
		                        			HIV Infections/therapy*
		                        			;
		                        		
		                        			HIV-1
		                        			
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail