Improvement in the 95-95-95 Targets Is Accompanied by a Reduction in Both the Human Immunodeficiency Virus Transmission Rate and Incidence in China.

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Recombinant characteristics of three novel HIV-1 second-generation recombinant forms composed of CRF01_AE and CRF07_BC isolated in Hebei province, China.

Human immunodeficiency virus 1 (HIV-1) is a fast-evolving, genetically diverse virus. The HIV-1 evolution rate is also significantly influenced by the frequency of HIV-1 spread in a population. Transmission via homosexual contact has become the predominant transmission route, leading to an increase in the HIV-1 epidemic in Hebei province, China. In this study, we report three novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from three men who have sex with men (MSM) in the cities of Shijiazhuang (20747) and Langfang (20809 and 20820). Phylogenetic analysis based on HIV-1 near-full-length genome (NFLG) sequences indicated that the three novel recombinant forms formed a distinct monophyletic branch that was separate from all known HIV-1 subtypes and circulating recombinant forms (CRFs). Breakpoint analysis showed that the three NFLGs displayed different recombinant patterns. NFLGs 20747 and 20809 had a recombinant pattern with subtype CRF01_AE gene fragments inserted into a CRF07_BC backbone, spanning from the gag to env gene regions, whereas NFLG 20820 had a recombinant pattern with subtype CRF07_BC gene fragments inserted into a CRF01_AE backbone. Subregion phylogenetic analysis confirmed that these three NFLGs comprised CRF01_AE and CRF07_BC. Our findings confirm the emergence of novel recombinant forms and highlight the need for continuous monitoring of the diversity of HIV-1 among sexually active populations, especially MSM, to better control the HIV-1 epidemic.

Genome mosaic structure of two novel HIV-1 recombinant forms (CRF01_AE/B) in men who have sex with men in Hebei, China.

BACKGROUND: Homosexual contact is the main route of human immunodeficiency virus type one (HIV-1) transmission in Cangzhou Prefecture, Hebei, China. Moreover, the number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in this key population is ever increasing. METHODS: In this study, we identified two novel URFs (hcz0017 and hcz0045) from two men who have sex with men (MSM) based in Cangzhou Prefecture. Phylogenetic and recombinant breakpoint analyses, based on the near full-length genomes (NFLGs) of the two novel URFs, showed that they originated from a recombination between HIV-1 CRF01_AE and subtype B. RESULTS: HXB2 numbering revealed that the NFLGs of hcz0017 and hcz0045 each contained the following seven subregions: hcz0017: IB (790-1,171 nt), IICRF01_AE (1,172-2,022 nt), IIIB (2,023-4,469 nt), IVCRF01_AE (4,470-5,866 nt), VB (5,867-7,462 nt), VICRF01_AE (7,463-8,379 nt), VIIB (8,380-9,411 nt); hcz0045: ICRF01_AE (790-5,147 nt), IIB (5,148-5,614 nt), IIICRF01_AE (5,615-6,035 nt), IVB (6,036-6,241 nt), VCRF01_AE (6,242-7,325nt), VIB (7,326-8,254 nt), VIICRF01_AE (8,255-9,411 nt). Moreover, the two MSM from whom the novel URFs originated from were diagnosed as recently HIV-1-infected, suggesting that the high prevalence of HIV-1 among MSM was related to high-risk sexual activity such as unprotected anal sex and multiple sexual partners. CONCLUSIONS: Our results highlight the need to continually monitor HIV-1 diversity in Hebei and its neighboring provinces to achieve a more effective control of HIV-1 spread within the MSM community.

Genetic characterization of a novel HIV­1 CRF01_AE/ CRF07_BC recombinant form found among men who have sex with men in Baoding City, Hebei Province, China.

Large numbers of unique recombinant forms (URF) of human immunodeficiency virus (HIV-1) have been found among sexual transmission populations in China. Here, we report a novel second-generation URF of HIV-1 named BD201AQ that was isolated from an HIV-1-positive man who was infected through homosexual transmission in Baoding City, Hebei Province, China. Phylogenetic analysis based on the near-full-length genome (NFLG) sequence indicated that BD201AQ formed a monophyletic branch that did not cluster with other HIV-1 subtypes. Recombination analysis showed that the NFLG of BD201AQ had 12 segments, six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. These findings indicate that the constant emergence of novel recombinant forms should receive more attention and that more measures should be taken to monitor the molecular epidemiological characteristics of HIV-1 and to prevent the spread of HIV-1 infections.

HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China.

BACKGROUND: To understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey. METHODS: Blood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected. Genotyping of HIV-1 drug resistance (DR) was implemented using an in-house assay. RESULTS: In this study, the overall prevalence of HIV-1 DR was 35.5%. The prevalence of HIV-1 DR in participants experiencing treatment failure and ART-naïve participants was 51.9 and 5.9%, respectively. Mutations in protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTI (NNRTIs), as well as dual and multiple mutations were extensively seen in participants experiencing treatment failure. The proportions of NNRTI mutations (χ2 = 9.689, p = 0.002) and dual mutations in NRTIs and NNRTIs (χ2 = 39.958, p < 0.001) in participants experiencing treatment failure were significantly higher than those in ART-naïve participants. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. Viral load, symptoms in the past 3 months, CD4 counts, transmission route, and the duration of ART were found to be associated with HIV-1 DR. CONCLUSIONS: Our results suggest that new prevention and control strategies should be formulated according to the epidemic characteristics of HIV-1-resistant strains in Hebei Province, where antiretroviral drugs are widely used.

HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China.

BACKGROUND: Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. METHODS: Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. RESULTS: Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P < 0.05), occupation (P < 0.05) and ethnicity (P < 0.05). The distributions of subtype B (P < 0.05), CRF01_AE (P < 0.05), CRF07_BC (P < 0.05) and subtype C (P < 0.05) showed significant differences in all ten prefectures, and the distributions of all six subtypes were significantly different in Shijiazhuang (P < 0.05) and Xingtai (P < 0.05), but not in other prefectures (P > 0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. CONCLUSIONS: Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.

Eighteen-year follow-up report of the surveillance and prevention of an HIV/AIDS outbreak amongst plasma donors in Hebei Province, China.

BACKGROUND: There has been a clear increase in HIV-1 infection cases in recent years in Hebei Province, China, and transmission via blood is one of the risk factors in the early. This article aimed to investigate the HIV infection rate and control efficiency among the paid blood donor population over a period of 18 years. METHODS: From 1995-2013, HIV/AIDS cases among former blood donors in Hebei Province were registered and closely monitored to collect data of all-cause mortality, intervention measures to prevent family transmission, disease transmission between couples as well as between mothers and infants, and HAART therapy outcomes. RESULTS: A total of 326 cases were identified as directly infected with HIV/AIDS during plasma donation in Hebei Province. Of these, 146 cases (44.8%) were identified in the same year as infection; 180 cases (55.2%) were identified 1-18 years after infection because they did not participate in the 1995 screening. The final case was identified in February 2012. By 2013, the mortality rate and survival rate of plasma donor-related HIV/AIDS was 54.9% and 45.1%, respectively. The identified transmission rate between couples was 11.3% (8/71); this rate during the same year as infection was 3.3% (1/30), and the rate 4-17 years after HIV infection was 17.1% (7/41). Approximately 91.2% (145/159) of married women of childbearing age did not have children after being informed of HIV infection. Only 8.8% (14/159) of these women had children after being informed of HIV infection. The mother-to-infant transmission rate was 38.5% (5/13). The HAART coverage rate has increased from 10.1% (16/159) in 2003 to 83.6% (127/152) in 2013. Since 1999, the HIV mortality rate has trended up; by 2013, the cumulative mortality rate reached 54.9% (179/326). After HAART was initiated in China, the death rate decreased to some extent. Second generation transmission (via couple or mother-to-infant transmission) among blood donor-related HIV cases accounted for approximately 4.0% (13/326). All first- or second-generation cases were infected with HIV-1 subtype B. CONCLUSIONS: In this accident of HIV-infection among plasma donors in Hebei Province, a total of 339 direct and second-generation cases have been identified over 18 years of monitoring. Favorable clinical results have been achieved using intervention measurements and antiviral therapy.

Identification of Two HIV-1 CRF01_AE/B Recombinant Forms and a CRF01_AE/B/C Recombinant Form in Hebei Province, China.

BACKGROUND: In the Hebei province, Human Immunodeficiency Virus type one (HIV-1) recombinant strains of subtypes B, C, and CRF01_AE are emerging very rapidly and diversely. OBJECTIVE: In order to confirm the characteristics of novel recombination forms, we aimed to analyze HIV-1 Near-full-length Genome sequences (NFLGs) obtained from three Men who have Sex with Men (MSM) in this study. METHOD: Phylogenetic trees were constructed and breakpoints analysis was performed based on the NFLGs and each gene fragment to examine the gene recombination patterns of three new HIV-1 NFLGs. RESULT: HIV-1 subtypes CRF01_AE and B were combined to generate the recombinant structures of the NFLGs 610 and 687. CRF01_AE, B, and C were combined to generate the recombinant structures of the NFLG 825. According to the NFLG phylogenetic tree, the NFLG 825 clustered with CRF65_cpx and the NFLGs 610 and 687 clustered with CRF68_01B. The recombination breakpoints analysis revealed that the recombination pattern of the NFLGs 610 and 687 was the insertion of subtype B fragment into the CRF01_AE backbone. Subregions I, II, and III were derived from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination pattern of the NFLG 825 contained ten fragments of subtypes CRF01_AE, C, and B. Finally, the above factors were formed using phylogenetic trees and breakpoints analysis, which were combined to get two CRF68_01B forms and one CRF65_cpx form. CONCLUSION: Our findings have suggested that it is crucial to keep an eye on the genetic diversity of HIV-1 in Hebei province.

Identification of a new HIV-1 circulating recombinant form (CRF159_01103) derived from CRF103_01B and CRF01_AE in Hebei Province, China.

Recombinant HIV-1 genomes identified in three or more epidemiological unrelated individuals are defined as circulating recombinant forms (CRFs). CRFs can further recombine with other pure subtypes or recombinants to produce secondary recombinants. In this study, a new HIV-1 intersubtype CRF, designated CRF159_01103, isolated from three men who have sex with men with no epidemiological linkage, was identified in Baoding city, Hebei Province, China. CRF159_01103 was derived from CRF103_01B and CRF01_AE. Bayesian molecular clock analysis was performed on the CRF01-AE and CRF103_01B regions of CRF159_01103. The time of origin of CRF159_01103 was predicted to be 2018-2019, indicating that it is a recent recombinant virus. The emergence of CRF159_01103 has increased the complexity of the HIV-1 epidemic in Hebei Province.

Epidemic trend, genetic characteristics, and transmission networks of HIV-1 among treatment-naive men who have sex with men in Hebei province, China.

Introduction: Homosexual transmission has contributed greatly to the current HIV-1 epidemic in Hebei province, China. Dolutegravir (DTG) will be conditionally used as a component of free antiretroviral therapy (ART) according to manual for national free anti-AIDS treatment drugs (2023 edition) issued by China in June 2023. However, current genetic characteristics and pretreatment drug resistance (PDR) to proteinase inhibitors (PIs), reverse transcriptase inhibitors (RTs) and integrase strand transfer inhibitors (INSTIs) of HIV-1 in this population have remained unclear. Methods: Serial consecutive cross-sectional analyses for HIV- 1 infection trend, genetic characteristics, PDR and molecular transmission networks were conducted from 2018 to 2022. All of participants were HIV-1- infected MSM newly diagnosed at the HIV surveillance points (HSPs) in Hebei, China. Evidence of PDR was confirmed using the world health organization (WHO) list for surveillance of drug resistance mutations. Results: In this study, a total of 14 HIV-1 subtypes were circulating in the HSPs of Hebei province, China. CRF01_ AE (51.9%, 350/675), CRF07_BC (30.4%, 205/675), B (6.2%, 42/675) and URFs (5.8%, 39/675) were the four most predominant subtypes among MSM. And, CRF07_BC (r > 0) and URFs (r > 0) indicated an increasing trend, respectively; however, CRF01_AE (r < 0) showed a decline trend. The overall prevalence of HIV-1 PDR showed a substantial increase from 6.3% in 2018 to 7.9% in 2022. The prevalence of NNRTI-PDR was the highest (5.8%, 39/675), followed by INSTIs (2.4%, 16/675), NRTIs (0.6%, 4/675) and PIs (0.3%, 2/675). Furthermore, extensive HIV-1 strains bearing PDR were circulating in the MSM population via molecular transmission networks for major HIV-1 subtypes, especially CRF01_AE and CRF07_BC. Discussion: Our findings reflect that HIV-1 epidemic in the MSM population is complex and severe in Hebei, China. Therefore, it is urgent for us to implement more effective intervention measures to limit the further dissemination of HIV-1, especially the spread of HIV-1 INSTI-PDR strains.

Near-Full-Length Genome Analysis of a HIV-1 CRF01_AE/B Recombinant Strain Among Men Who Have Sex with Men in Chengde City, China.

The unique recombinant form (URF) of HIV is formed by multiple subtypes which are cocirculating in some area, and the number of HIV recombinants is on the increase worldwide. In this study, we identified a URF named 2019638, composed of CRF01_AE and subtype B, in a man who has sex with men in Qinhuangdao, Hebei province, China. The near-full-length genome (NFLG) sequence was confirmed to be a novel URF. Within this NFLG, two CRF01_AE fragments were inserted into the pol and vif regions, respectively, using subtype B as the backbone. Moreover, the presence of the V106M and V179D point mutations in the reverse transcriptase (RT) region rendered the high-level resistance to efavirenz and nevirapine and intermediate resistance to doravirine. Our findings suggest that the HIV epidemic is evolving toward a high degree of recombination, and we need to continuously monitor HIV genetic diversity to control the further development of the AIDS epidemic.

Three Novel CRF01_AE/CRF07_BC Recombinant Forms of HIV-1 Identified in Shijiazhuang City, China.

BACKGROUND: Hebei, a province with a low Human Immunodeficiency Virus (HIV) prevalence, is also a region with the most abundant HIV-1 genetic diversity. HIV-1 recombinant forms have been the key factor influencing the effectiveness of HIV-1 control and therapy. OBJECTIVES: We aimed to study inter-subtype recombinant structures of new HIV-1-second generation recombinant forms. METHODS: Monitoring the HIV-1 subtype by phylogenetic and recombinant breakpoint analyses are the two most frequent methods among men who have sex with men (MSM). Here, three near full-length genomes (NFLGs) were obtained from HIV-1 seropositive MSM in Shijiazhuang City, China, who have never received antiretroviral therapy in 2021. RESULTS: Phylogenetic analysis indicated that three NFLGs were novel inter-subtype recombinant forms between CRF07_BC and CRF01_AE. For the NFLG 21S009, four CRF07_BC gene fragments were inserted into the pol, vif-vpr, vpu-env, and nef-3` LTR gene regions within a CRF01_ AE backbone, respectively. For the NFLG 21S095, four breakpoints were identified in HIV-1 pol and vpu regions. The NFLG 21S370 contained four gene recombinant breakpoints within HIV-1 pol and vpu-env gene regions. Of these three NFLGs, the NFLG 21S009 contained the most breakpoints, distributed in the pol, vif, vpr, vpu, env, and nef regions, respectively. In the gag-pol regions, three NFLGs had only one CRF07_BC gene fragment inserted into gene points between 4250 and 4792. CONCLUSION: Our findings provide strong evidence that the surveillance of novel recombinant forms is necessary for the increase in better control of HIV.

Identification of Two Novel HIV-1 Recombinant Forms Originated from CRF01_AE and Subtype B in the Sexual Contact Population in Hebei Province, China.

Two near full-length genome (NFLG) sequences of HIV-1 with undefined subtypes were analyzed to confirm the recombinant characteristics. To analyze the gene recombination patterns and breakpoints of these two NFLGs, the phylogenetic trees based on the NFLG sequences and their subregions were constructed, respectively. Sequences 233 and 953 are novel second-generation recombinant forms of HIV-1 CRF01_AE and subtype B. The NFLG phylogenetic tree analysis showed that these two NFLG sequences formed a unique monophyletic branch, respectively. The recombination breakpoints analysis showed that the recombination pattern of both sequences was that a subtype B fragment was inserted into a CRF01_AE backbone. Subregions I, II, and III were from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination breakpoints relative to HXB2 of sequences 233 and 953 were 2400 and 4870, and 3363 and 4828, respectively. The emergence of novel recombinant forms of CRF01_AE/B demonstrates that we should carry out the ongoing surveillance of HIV-1 recombinant forms in the sexually transmitted population.

Identification of two near-identical novel HIV-1 unique recombinant forms (CRF01_AE/B) among men who have sex with men in baoding, hebei, China.

Men who have sex with men (MSM) are the most frequent infection route of the human immunodeficiency virus (HIV) in Baoding, China, creating chances for the occurrence of unique recombinant forms (URFs) of the virus, i.e., recombination of different subtypes caused by co-circulation of multiple subtypes. In this report, two near-identical URFs (BDD002A and BDD069A) isolated from MSM in Baoding were identified. Phylogenetic tree analysis based on nearly full-length genomes (NFLGs) revealed that the two URFs formed a distinct monophyletic cluster with a bootstrap value of 100%. Recombinant breakpoints analysis identified that the NFLGs of BDD002A and BDD069A were both composed of CRF01_AE and subtype B, with six subtype B mosaic segments inserted into the CRF01_AE backbone. The CRF01_AE segments of the URFs clustered closely with the CRF01_AE reference sequences, and the B subregions clustered with the B reference sequences. The recombinant breakpoints of the two URFs were almost identical. These results suggest that effective interventions are urgently needed to prevent the formation of complex HIV-1 recombinant forms in Baoding, China.

Near-Full-Length Genomic Characteristics of Three Novel Human Immunodeficiency Virus-1 CRF01_AE/C Recombinant Forms Among Men Who Have Sex with Men in Hebei Province, China.

Subtypes circulating recombinant form (CRF)01_AE and C are two human immunodeficiency virus (HIV)-1 strains that are prevalent in different key populations such as men who have sex with men (MSM) in China. Co-circulating of different HIV-1 subtypes is easy to result in the generation of second-generation recombinants. In this study, three new HIV-1 CRF01_AE/C recombinants from three MSMs were detected in Hebei province, China. Phylogenetic tree and recombination analysis showed that the near-full-length genomic of S114 had seven recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone; M363 had six recombination breakpoints, including three C fragments inserted into the CRF01_AE backbone; M162 had eight recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone. Furthermore, phylogenetic tree analysis based on subregion gene fragments also identified this kind of CRF01_AE/C recombinant structure. This study suggests a more complex HIV-1 epidemiological trend in Hebei province, China and the urgency of continuous HIV-1 recombinant strain registry in sexually transmitted populations.

Changes of Viral Load, Drug Resistance, and CD4 Cell Count in HIV-1-Infected Patients Receiving Antiretroviral Therapy in Hebei Province, China, 2003-2019.

In this study, a total of 462 samples of whole blood were collected from 36 patients enrolled. During the entire course of antiretroviral therapy (ART) from 2003 to 2019, both the CD4 cell count and viral load (VL) of study patients were examined annually, and an HIV-1 genotypic drug resistance (DR) assay was carried out using an in-house method when the HIV-1 VL was >1,000 copies/mL. The results indicated that 13 (36.1%) experienced treatment failure and 23 (63.9%) experienced treatment success among 36 patients. The proportion of patients with effective treatment after the adjustment of ART regimens was significantly higher than before adjustment (χ2 = 33.796, p < .001). Furthermore, the frequencies of HIV-1 DR mutations before adjustment were higher than those after adjustment (t = 3.345, p = .002). In particular, among 23 patients with effective treatment after adjustment, the means ± standard deviations of the VLs and CD4 cell counts before adjustment were 3.85 ± 0.65 log RNA copies/mL and 226.83 ± 106.06 cells/mm3, respectively, compared with 2.19 ± 0.58 log RNA copies/mL and 367.68 ± 174.62 cells/mm3, respectively, after adjustment. Obviously, there were statistically significant differences in the changes in VL (t = 8.728, p < .001) and CD4 cell count (t = -4.476, p < .001) before and after adjustment. Therefore, patients who received updated ART regimens containing LPV/r and TDF after adjustment achieved better therapeutic effects compared with patients who received initial ART regimens harboring D4T/AZT or NVP. This suggests that future research is needed to initiate the surveillance of DR, VLs, and CD4 cell counts immediately after HIV diagnosis, and dynamic changes in these indicators so as to optimize ART effects.

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.

[Retrospective cohort study on period of incubation and survival among former commercial plasma donors infected with HIV in Hebei province].

OBJECTIVE: To examine the state of incubation period and survival time of former commercial plasma donors (FCPDs) infected with HIV. METHODS: All objects infected with HIV were from Hebei province and found from general investigation for FCPDs in 1995. The infector cohort by 142 cases was used to estimate incubation period. In the infector cohort, the time which infectors entered the cohort was their infection time, which was the middle value of the origin date, which was January 1, 1995. The onset of AIDS was defined as an outcome event. End point of observation was Dec 31, 2010. There were 192 months in all from beginning to end. The AIDS cohort by 57 cases was used to estimate the survival of the patients. In the patient cohort, the time of AIDS onset was defined as the time entering the cohort, and death of AIDS was defined as an outcome event. The cumulative incidence ratio, cumulative mortality, illness intensity and mortality intensity were analyzed through Kaplan-Meier. RESULTS: During the observation period, 123 cases of 142 infectors developed into AIDS, the cumulative incidence was 86.42% (123/142) and the intensity was 8.53/100 person-years and the median time of incubation period was 112.0 months (95%CI: 108.8 - 115.2). The death dates of 57 patients were from 1 to 24 months after onset. The cumulative mortality was 100%, and the intensity was 250.66/100 person-years and the median survival time was 3.0 months (95%CI: 1.8 - 4.2). It was estimated that the median time was 115.0 months (9.6 years) from infection to death. CONCLUSION: The median times of incubation and median survival time were 112.0 and 3.0 months, respectively.

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma.

Objective: To explore the efficacy, safety, and patient prognosis of letrozole (LTZ) alone or in sequence with tamoxifen (TAM) for the treatment of breast carcinoma (BC). Methods: In this retrospective study, 150 patients with BC who received treatment in the First People's Hospital of Ningyang County between January 2012 and January 2017 were selected. According to different treatment methods, 99 cases receiving sequential therapy with TAM and LTZ were included in the research group, and the remaining 51 patients receiving LTZ monotherapy were selected as the control group. The efficacy, safety, survival rate, recurrence rate, and blood lipid indices (total cholesterol, TC; triglyceride, TG; high-density lipoprotein cholesterol, HDL-C; and low-density lipoprotein cholesterol, LDL-C) of the two groups were observed and compared. Results: The overall response rate of the research group was statistically higher than that of the control group, and the incidence of adverse reactions was significantly lower. No evident difference was observed in 1-, 3-, or 5-year survival rates between the two groups, while the 3-5-year recurrence rate was obviously lower, and the improvement of blood lipid indices was significantly better in the research group compared with the control group. Conclusion: LTZ alone or in sequence with TAM is effective and safe for the treatment of BC, which can significantly improve the prognosis and blood lipid indices of BC patients.