[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.

Pretreatment HIV drug resistance in adults initiating antiretroviral therapy in China, 2017.

BACKGROUND: After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China. METHODS: Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR. RESULTS: In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57-4.44) and individuals from Liangshan, Dehong, and Lincang (aOR = 2.04, 95% CI: 1.26-3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong. CONCLUSIONS: Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China.

OBJECTIVES: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. METHODS: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. RESULTS: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3-96.7) was significantly higher than that in group 1 (1.4%, 95% CI -1.4 to 4.2; χ2 = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 106 copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. CONCLUSION: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.

The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

[Distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region, 2008-2009].

OBJECTIVE: To understand the distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region. METHODS: 294 participants who were infected by HIV-1 in 2008 - 2009 and residing in 13 cities in Guangxi were enrolled into this study. Epidemiological information showed that heterosexual transmission was the main transmitting route. 1584 bp full length gag gene, 3147 bp full length pol gene and 558 bp env (C2V3) fragments were amplified by using RT-PCR and then directly sequenced. NCBI genotyping tool and Mega 5.03 software were used to determine the HIV subtypes. Simplot and Recombinant HIV-1 Drawing Tool were used for the analysis of recombination. RESULTS: A total of 739 sequences, including 270 gag, 246 pol and 223 env (C2V3), were successfully obtained from 294 plasma specimens. Genotypes of HIV from 272 participants were determined. CRF01_AE was found the dominant (77.6%), followed by CRF08_BC (10.7%) and CRF07_BC (7.4%). 7 unique recombinant forms, 4 subtype B (B') and 1 subtype G were also identified. No significant difference on the distribution of subtypes among different regions and ethnics was found. Among the 7 unknown recombinant forms, 6 strains were mosaic B and/or C fragments with CRF01_AE genome as the backbone, while one strain originated from CRF07_BC and CRF08_BC. CONCLUSION: Currently, CRF01_AE was found the major subtype of HIV epidemic in Guangxi. New recombinant forms with CRF01_AE as backbones had been emerging, which called for serious attention.

[The changes and significance of T lymphocytes and subsets before and after receiving highly active anti-retroviral therapy in children infected with HIV or AIDS patients].

OBJECTIVE: To investigate the changes of the T lymphocytes and their subsets before and after receiving highly active anti-retroviral therapy (HAART) in children who were infected with HIV or AIDS patients. METHODS: Ninety-nine children met the criteria were recruited. All of them had received HAART in Guangxi Center for Disease Control and Prevention from May 2006 to April 2009. Peripheral blood of 2 milliliter was collected before treatment (D0) and after 3, 6, 12, 18, 24, 30, and 36 months (M3, M6, M12, M18, M24, M30 and M36), respectively. Four-color fluorescence flow cytometry was used for the detection of the absolute numbers of CD3(+), CD4(+), CD8(+) T lymphocytes in peripheral blood. And then, the percentages of CD3(+), CD4(+), CD8(+) T lymphocytes in the CD45(+) cells and the ratio of CD4/CD8 were calculated. RESULTS: Sixteen-five (65.66%) cases were treated with lamivudine (3TC)/zidovudine (AZT)/nevirapine (NVP), and 16 (16.16%), 8 (8.08%) and 10 (10.10%) cases were treated with 3TC/stavudine (D4T)/NVP, 3TC/AZT/efavirenz (EFV) and 3TC/AZT/lpv-rtv (LPV/r), respectively. The median of the ratio of CD4/CD8 were 0.39, 0.51, 0.61, 0.65, 0.70, 0.73 and 0.76 in M3, M6, M12, M18, M24, M30 and M36, respectively which were significantly higher than that in D0 (0.19) (Z values were -5.158, -7.375, -9.078, -8.853, -8.373, -5.845 and -5.844 respectively, P < 0.000). The median of CD4% were 16.92%, 22.70%, 25.54%, 26.66%, 27.99%, 30.36% and 29.30% respectively in M3, M6, M12, M18, M24, M30 and M36 respectively, which were also higher significantly than that in D0 (9.92%) (Z values were -5.268, -7.568, -9.496, -9.171, -8.760, -6.190 and -5.964 respectively, P < 0.000). In addition, the median of the absolute numbers of CD4(+)T lymphocytes in peripheral blood were 631, 813, 1050, 946, 1057, 1166 and 894 cells/mm(3) respectively in M3, M6, M12, M18, M24, M30 and M36, which were higher significantly than that of D0 (382 cells/mm(3)) (Z values were -3.318, -5.288, -6.661, -5.886, -5.801, -4.110 and -3.600 respectively, P < 0.000). However, the median of CD8% were 47.25%, 43.01%, 43.04%, 42.60%, 41.37%, 40.83% and 38.31% respectively in M3, M6, M12, M18, M24, M30 and M36, which were lower significantly than that of D0 (53.17%) (Z values were -3.082, -4.697, -5.282, -5.846, -5.757, -3.883 and -4.380 respectively, P < 0.001). CONCLUSION: There is certain rules for the changes of T lymphocytes and their subsets, which may play important roles in the evaluation of the therapeutic effect and the clinical application guidance of HAART.

[Genetic characteristics of HIV-1 CRF01_AE strains in four provinces, southern China].

OBJECTIVE: To analyze the genetic characteristics of HIV-1 CRF01_AE strains prevailing in the four provinces of southern China. METHODS: Plasma samples were collected from the newly diagnosed HIV-1 individuals reported in 2006 in Guangdong, Guangxi, Jiangxi and Hunan province. The gag and env gene fragments were amplified from RNA template extracted from plasma using RT and nested PCR methods. CRF01_AE sequences were analyzed by phylogenetic methods and characterized by calculating the genetic distance and Entropy analysis. RESULTS: Two main epidemic clusters were found to exist in the CRF01_AE strains from 210 HIV-1 CRF01_ AE infected individuals collected in the 4 provinces, southern China. It was found that no international reference strain was closely correlated with cluster I, which including 123 samples. The strains in cluster II, consisting 57 cases of samples, were closely related with the strains identified in Vietnam. Genetic distance analysis of gag and env genes showed that the diversity of cluster I was obviously less than that of cluster II. Data on nucleotide polymorphism showed that nucleotides compositions of 42 sites in gag and 40 sites in env were significantly different between the two clusters. When compared with cluster II, the polymorphism decreased at 61 nucleotide sites but increased at 21 sites in cluster I. CONCLUSION: This was the first report describing that two main epidemic clusters were existed in CRF01_AE strains prevailing in the 4 provinces, Southern China. The virus in cluster I was the dominant strain in this region, with shorter period of circulation and higher proportion seen in the HIV-infected population, which might belong to CRF01_AE strain with certain features facilitating the spread of the virus. The virus in cluster II was highly homology with the CRF01_AE strains from Vietnam, and seemed to have had several events of epidemics in populations in border regions of China and Vietnam.

[Study on the antiviral therapy program among people with human immunodeficiency virus in Guangxi Zhuang Authority].

OBJECTIVE: To explore the reconstitution of immune function and viral suppression condition and to analyze the occurrence of drug resistance HIV-1 variants and its prevalence after using HAART in Guangxi Autonomy Region. METHODS: From July 2004 to October 2005, 133 HIV infected individuals who had received HAART for more than three months were recruited, and 58 infected persons with no antiviral therapy were selected as controls. Questionnaire was used to collect information about the adherence of HAART therapy. Immune reconstruction and viral suppress conditions were obtained by CD4+ counts and viral load and RT-PCR were used to amplify the PR and RT regions of HIV-1 genome while HIV-1 drug resistance rates were analyzed to show the occurrence and prevalence in both treated and naive patients. RESULTS: In terms of CD4+ T cell counts: 70.69% of the treated patients showed obvious increase and 23.28% had no apparent change but 6.03% of them went down. 70.48% of the patients who had received antiviral therapy more than 3 months had their viral load lower than the low detectable limitation. When comparing the log of viral load between treated and untreated cohort, the mean value of the treated was obviously less than the untreated (P < 0.05). However,the result of drug resistance showed no obvious difference between the treated and untreated groups. CONCLUSION: The antiviral therapy being used in Guangxi region, had achieved obvious effect on the reconstruction of immune system and the suppression of viral replication in vivo under good adherence while the occurrence of drug-resistant HIV strain did not show obvious difference between treated and naive patient groups.