Primary drug resistance among HIV-1 patients in Hubei Province in 2020-2022 / 公共卫生与预防医学

Objective To investigate the prevalence of primary drug resistance among HIV-1 patients in Hubei Province from 2020 to 2022, and to provide corresponding basis and data support for HIV antiviral therapy (ART) in Hubei Province. Methods During 2020-2022, plasma samples of HIV-1 infected patients before ART were collected., Patients’ demographic data and baseline laboratory test data were also collected. HIV-1 pol region was amplified by in-house method for sub-type typing and drug-resistant mutation site analysis. Results The pol gene sequence was successfully amplified in 242 of 285 cases, with a success rate of 84.9%. CRF07_BC was the predominant HIV-1 sub-type, accounting for 47.11% (114/242), followed by CRF01_AE, accounting for 25.21% (61/242), sub-type B, accounting for 14.16% (35/242), and CRF55_01B, accounting for 4.13% (10/242). The primary resistance rate was 6.20% (15/242). The mutation site of nucleoside reverse transcriptase inhibitors (NRTIs) was mainly M184V, and the mutation sites of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were mainly E138A/G/EG and V179E. These different mutation sites led to different degrees of drug resistance to 12 drugs. The incidence of drug resistance mutation of CRF55_01B sub-type was significantly higher than that of other sub-types. Conclusion The primary drug resistance rate of HIV-1 infected patients is at a slightly high level in Hubei Province, and close monitoring of primary drug resistance and mutation sites should be strengthened before ART, especially for CRF55_01B sub-type.

A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer / 中华肿瘤杂志

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

Primary drug resistance to integrase inhibitors among newly diagnosed HIV infected patients in Shenyang city / 临床检验杂志

Objective@#To explore the transmission of integrase inhibitors (InIs) resistant strains among newly diagnosed HIV-1 infected individuals in Shenyang city. @*Methods@#Eighty newly diagnosed HIV infected individuals were retrospectively collected in Shenyang from June 2018 to March 2019. The sequences of integrase-encoding genes were amplified from the viral RNA in plasma. The viral genotypes were analyzed with phylogenetic method and the mutations of drug resistance genes were interpreted according to the algorithm of Stanford HIV drug resistance database. The primary drug resistance rates were calculated and natural polymorphisms on InIs resistance sites in different subtypes of the virus strain were analyzed. @*Results@#Among the 80 HIV-1 infected individuals, 51, 14 and 6 cases were genotyped as HIV CRF01_AE, CRF07_BC and subtype B respectively, accounting for 63.8%,17.5% and 7.5%. Nine cases (11.3%) were classified as atypical HIV-1 recombinants. R263K mutation was detected in two CRF01_AE infected patients, and E138A mutation was detected in a patient infected with subtype B. The overall drug resistance rate for InIs was 3.8%. CRF01_AE infected individuals showed amino acid polymorphism at the site 50, 74, 119 and 153 relevant to InIs resistance with frequency of 5.9%, 2.0%, 13.7% and 4.0% respectively. The CRF07_BC infected individuals showed amino acid polymorphism at the site 50, 74 and 157 relevant to InIs resistance with frequency of 7.1% for each site. @*Conclusion@#The primary drug resistance rate of InIs among the newly diagnosed HIV infected people in Shenyang was low, but a small number of patients showed amino acid polymorphisms on InIs resistance sites. To interpret the significance of drug resistance mutations in InIs better, it is necessary to strengthen both the monitoring of HIV InIs resistance and the study on the drug resistance-relevant genotype and phenotype of HIV-1 strains epidemic in China.

Subtypes and primary drug-resistant gene mutations in HIV-1 infections in Jiangyin / 中华实验和临床病毒学杂志

Objective@#To investigate the subtypes and primary drug resistant (PDR)mutations among HIV-1 infected population in Jiangyin.@*Methods@#Anticoagulated blood samples were collected from HIV infected individuals confirmed and managed by Jiangyin CDC from 2013-2015, and epidemiological data were analyzed. The pol gene was amplified by nested-PCR from the DNA extraction and then sequenced. Phylogenetic tree was constructed to determine the subtypes of the samples. PDR mutations and viral susceptibility to ARTs were interpreted with the Surveillance Drug Resistance Mutations (SDRM)list recommended by WHO and Stanford University HIV Drug Resistance database.@*Results@#The pol gene of 100 cases was successfully amplified and sequenced among 111 samples enrolled in this study, 7 different subtypes were found by phylogenetic tree analysis and CRF01_AE(44/100), CRF07_BC(21/100), CRF67_01B(14/100)subtypes accounted for the main part. Fourteen participants (14/100)met the WHO guidelines of having HIV-1 PDR. NRTI, NNRTI, PI PDR mutation rates were 3.0%, 7.0%, and 6.0%, respectively. Nine cases of the 14 infections with PDR presented clinical DR and the resistance rate was 8.1%, of which CRF01_AE accounted for the main part (5/9).@*Conclusions@#The prevalence of HIV-1 infections of different subtypes in Jiangyin city varied and there was a certain proportion of primary drug resistance. Corresponding drug resistance testing should be carried out for new HIV infections before treatment and reasonable antiviral treatment plan should be formulated, which will reduce the emergence of drug-resistant strains ultimately.

Advances in drug resistance mechanism of immunological checkpoint inhibitors and post-drug resistant therapeutic strategy / 实用肿瘤学杂志

Immune-checkpoint blockers(ICBs)have been well received in a variety of tumors,and the quality of patient life has improved significantly.However,the reasons why not all patients treated with ICBs benefit from lesion control,symptom improvement,and survival time.Many patients are resistant to the first time when they have been using ICBs for a period of time.This is a clinical challenge.This review lists possible causes of primary drug resistance and acquired resistance to ICBs.The primary resistance is associated with several mechanisms,including tumor microenvironment,cancer cells themselves and other related factors.The acquired resistance includes nonclassical immunoprecipitation molecules secondary overexpression,abnormalities of antigen presenting signal pathway and dysfunction of T cell activation killer.Finally,we have described a variety of possible new combination of treatment,including combined radiotherapy and chemotherapy,and combined targeted therapy with other measures.

HIV resistance in men who have sex with men: a Meta-analysis / 中南大学学报(医学版)

Objective:To assess the prevalence of HIV primary drug resistance and drug resistance gene mutations among men who have sex with men (MSM).Methods:We searched eight electronic databases (CNKI,VIP,CBM,Wanfang Database,PubMed,Web of Knowledge,Springer,Medline) for the studies of HIV drug resistance relevant to MSM.Drug resistance and drug resistance mutations data were pooled and analyzed according to statistical test of homogeneity.Subgroups were further divided according to sample size,location,race,quality rating score,sampling time.Results:Forty-three studies were included in this Meta-analysis.The pooled rate of total to protease inhibitor (PI),nucleoside reverse transcriptase inhibitor(NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) were 10.21％ (95％ CI 8.65％ to12.03％),2.98％ (95％ CI 2.25％ to 3.93％),4.05％ (95％ CI 3.14％ to 5.21％),4.42％ (95％ CI 3.31％ to 5.88％),respectively.The pooled rates of PI major mutation,PI secondary mutations,NRTI mutations and NNRTI mutations were 0.55％ (95％ CI 0.38％ to 0.80％),1.31％ (95％ CI 0.98％ to 1.75％),0.85％ (95％ CI 0.51％ to 1.40％),1.19％ (95％ CI 0.70％ to 2.01％),0.79％ (95％ CI 0.55％ to 1.13％),1.73％ (95％ CI 1.21％ to 2.46％),0.86％ (95％ CI 0.61％ to 1.21％),2.24％ (95％ CI 1.77％ to 2.83％),respectively.Sample size,region,and race were heterogeneous sources;the rate of resistance mutations and gene mutation rate were different in different subgroups.Conclusion:The prevalence of primary drug resistance among MSM was high in Americas and Europe,and it was gradually increased in Asia.We should pay attention to the high incidence of PI secondary mutations.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB).</p><p><b>METHODS</b>A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains.</p><p><b>RESULTS</b>Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation.</p><p><b>CONCLUSION</b>This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.</p>

Factors Affecting Discordance between Sputum Smear and Culture Conversion Rates In Newly Diagnosed Pulmonary Tuberculosis: A Retrospective Study in Developing Country.

Aims: To assess the performance of sputum AFB smear for monitoring treatment response and outcome of anti-tuberculous drugs among newly diagnosed smear positive pulmonary TB patients. Study Design: This study was conducted prospectively among newly diagnosed smear positive pulmonary TB patients. Place and Duration of Study: Queen Savang Vadhana Memorial Hospital and Chonburi Regional Hospital, Chonburi province, Thailand during April 2010 and July 2012. Methodology: Sputum AFB smear, culture and drug susceptibility test were performed at the time of diagnosis, the second and the fifth month of treatment. Baseline characteristic, clinical and laboratory parameters, treatment regimens and adverse events were recorded. Descriptive statistics and multiple logistic regression analysis were applied as appropriate. The performance of sputum AFB smear for monitoring treatment response and outcome of anti-tuberculous drugs was done using culture as the gold standard. Results: Of 297 eligible pulmonary TB cases, majorities were male (72.4%) with median age of 39 years, illiterate to low educated (52.6%) and earning low income (77.5%). Cough was the most common symptom (91.2%) and cavity was present in 31.1%. At the second month, 17.0% of patients had discordance between sputum AFB smear and culture. High bacilli load (adjusted OR=2.38, CI=1.09-5.18), and hearing alteration (adjusted OR=10.98, CI=1.79-67.28) were significant predictors. Hypoalbuminemia was significantly more severe in patients with false positive AFB smear (P=.04). Sensitivity and specificity for AFB smear were 44.7% and 89.6% at the second month and 57.1% and 97.5% at the fifth month, respectively. MDR-TB was diagnosed in 1.0% and success rate was 77.1%. Conclusions: Baseline AFB smear ≥ 2+ and hypoalbuminemia as well as adverse events during intensive phase are strongly recommended as the criteria to prioritize culture and DST for new smear positive pulmonary TB patients with positive AFB smear at the second and the third month of treatment in developing countries.

Primary multidrug-resistant tuberculosis and its control implications in the State of Amazonas, Brazil: report of 3 cases / Multirresistência primária da tuberculose e implicações no controle no Estado do Amazonas, Brasil: relato de três casos

The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.

O surgimento de resistência múltipla às drogas de primeira linha implica na utilização de fármacos de maior custo, com duração mais longa, maior complexidade e mais efeitos colaterais. Relatamos os casos de três pacientes com multirresistência primária aos tuberculostáticos. O portador de HIV evoluiu para óbito antes do resultado do teste de sensibilidade. Portanto, o diagnóstico precoce de tuberculose multirresistente e o tratamento adequado devem ser prioridades do Programa Nacional do Controle da Tuberculose, visando interromper a cadeia de transmissão. Além disto, é urgente que seja avaliada a substituição do método das proporções por técnicas mais modernas e mais rápidas.

Study on the evolution of the minor resistant mutations and the primary resistance in rural areas of Henan / 中华微生物学和免疫学杂志

Objective To evaluate the antiretroviral therapy(ART),analyze the prevalence of resistance in rural areas,Henan,and explore the presence of minor resistant variants in pre-ART.Methods One hundred and forty-nine AIDS patients initiating ART were recruited and investigated at intervals of 6 months. Method of In-house developed by our laboratory for genotypjc resistance test was to analyze the occurrence of resistance among the failure of ART,and the allele-specific real.time PCR(ASPCR)was used to detect the minor resistant variants at the baseline samples once the resistance occurred.Results Vimlload significantly decreased among the patients who received ART(t=275,P=0.0001),but the absolute counts of CD4+T lymphocytes had no significant change(t=1.765 168,P=0.0852).Rate of resistance among the patients of treatment failure was 4.88%.The result of ASPCR in the survey of baseline showed that the minor resistant variants of M184V were detected in 7 patients and mutation K103N presented in 5 patients.Conclusion The primary drug-resistant straias in the untreated patients were found in Henan,and they might develop the dominant resistance strains and bring about the failure of ART.

MDR - TB Current Status.

Drug resistant tuberculosis has been reported since the early days of the introduction of chemotherapy, but recently multi-drug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to control of tuberculosis. A review of 63 surveys conducted between 1985 and 1994 suggested that primary and acquired MDR-TB was between 0-10.8% and 0-48% respectively. However, the qualities of these studies were variable due to the lack of proper representativeness and size of population sampled, as well as lack of standardized laboratory methods in some of them. In 1994, WHO-IUATLD carried out a surveillance which concluded that the problem is global; the median prevalence of primary and acquired multi drug resistance was 1.4% (0-14.4%) and 13% (0-54.4%) respectively. A second WHO-IUATLD global project on drug surveillance carried out in 1996-1999 in 58 countries, found that the median prevalence of primary and acquired multi-drug resistance was 1% (0-14%) and 9% (0 - 48%) respectively. Current estimates report, the prevalence of primary and acquired multidrug resistance in India as 3.4% and 25% respectively.. It must be emphasized that optimal treatment of MDR-TB alone will not curb the epidemic. Efforts must be focused on the effective use of first line drugs in every new patient so as to prevent the ultimate emergence of multidrug resistance. The use of reserve drugs to cure multi-drug resistant tuberculosis and to reduce further transmission should be considered, but only as part of well structured programmes of tuberculosis control.

Epidemiological characteristics of patients with drug-resistant tuberculosis / 결핵

BACKGROUND: There is increasing concern in many countries about the problem of drug-resistant tuberculosis. Prevalence of primary drug-resistant tuberculosis is the optimal epidemiological indicator for long term monitoring of national tuberculosis control program. Our purpose was The purpose of our study is to assess clinical characteristics and socioeconomic status of patients with drug-resistant tuberculosis. METHODS: We studied 68 cases with durg-resistant Mycobacterium tuberculosis infection diagnosed at the Ewha Womans University Mokdong Hospital from March, 1995 to February, 2000. RESULTS: Patients with primary drug-resistant tuberculosis(PDR) were younger(39.6±16.3 years vs. 48.2±16.5 years; p<0.05), had more population of less than more were under the age of 40 years aged-group(62.9% vs. 36.4%; p<0.05) and were more highly educated than those with acquired drug-resistant tuberculosis(ADR)(38.9% vs. 11.1%; p<0.05). In patients with ADR, the rates of familial history of tuberculosis and living in a rented house residence in a rented house were increased higher than compared with to those of patients with PDR. Patients with ADR had more involved lobes(2.0±0.8 vs. 1.4±0.7; p<0.01) and longer treatment duration than those with PDR(18.3±7.2 months vs. 10.6±6.3 months; p<0.05). Patients with ADR showed larger numbers of resistant were resistant to more number of drugs, lower hospitalization rate and higher rate of self-interruption of medication than those with PDR. In patients with PDR, mono-drug resistance was increased, whereas poly-and multi-drug resistances were decreased compared with those with ADR. Resistance to isoniazid was the highest among antituberculosis drugs, and resistance to isoniazid in patients with ADR was higher than that in patients with PDR(90.9% vs. 71.4%; p<0.05). CONCLUSIONS: Patients with ADR were more likely to include more population be of lower socioeconomic class, and patients with PDR seem seemed to be young and socially active population. For control of drug-resistant Mycobacterium tuberculosis infection, proper isolation and prevention of patient with drug-resistant tuberculosis are needed.

Drug-Resistant Tuberculosis in Children

PURPOSE: Initial drug resistance of children with tuberculosis is a useful performance indicator of tuberculosis control programme in the concerned country because it represented infection transmitted from adult patients with either primary or acquired drug resistance. But there have been a few studies available. The present study was made to know the incidence of drug-resistant tuberculosis in hopes of selecting effective treatment regimens for the treatment of childhood tuberculosis. METHODS: Tuberculosis patients were selected from those whose cultures had been submitted to drug susceptibility testing in the Korean National Tuberculosis Association from Jan. 1987 to Jun. 1995. We have investigated the drug resistance and reviewed retrospectively the medical records of children. A total of 48 strains were tested for drug susceptibility. Of these cases medical records were available in one half and 22 patients did not have a history of previous antituberculosis therapy. RESULTS: 1) Of the 48 strains, 18 (37.5%) were resistant to 1 or more antituberculosis drugs. The 14 (29.2%) and 8 (16.7%) strains were resistant to isoniazid and rifampin, respectively. The 7 (14.6%) strains were resistant to both isoniazid and rifampin. 2) Of the 22 strains isolated from patients without previous therapy, 4 (18.2%) were resistant to 1 or more antituberculosis drugs. The 2 (9.1%) strains were resistant to isoniazid. There were no resistant strains to rifampin and to both isoniazid and rifampin. CONCLUSIONS: Primary resistance rate for isoniazid was 9.1%. These limited data suggested that four-drug regimens is indicated in childhood tuberculosis patients.

Primary drug resistance to mycobacterium tuberculosis in Siriraj Hospital.

Primary drug resistance to Mycobacterium tuberculosis was investigated from the Division of Tuberculosis, Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University during August 1991 – July 1992. There were 100 isolations of M.tuberculosis, 70 from male patients, the other 30 from female patients. In male patients the largest age groups were 21-30 and 31-40 years. The isolates were 93 percent from sputum, the other 7 percent were from bronchial wash, pus and ascetic fluid. In female patients the largest age group were 11-20 and 21-30 years. The isolates were 83 percent from sputum, the other 17 percent were from brochial wash, pus and pleural fluid. The overall rate of resistance to antituberculosis drugs in this study was 37 percent. The isolates from sputum showed resistance to INH 22 percent and 13 percent, SM 9 percent and 8 percent, EMB 20 percent, RF 9 percent and 8 percent, the isolates from miscellaneous specimen (other than sputum) showed resistance only to INH (20% and 10%). Comparing this result with other reported data revealed that this study showed higher incidence of primary drug resistance to M. tuberculosis.