HIV-1 transmitted drug resistance in Brighton, UK, from 2014 to 2020

2020 ◽  
pp. 095646242095304
Author(s):  
Daniel Richardson ◽  
Colin Fitzpatrick ◽  
Luke Parkes ◽  
Jonathan Roberts ◽  
Larissa Mulka

HIV-1 transmitted drug resistance (TDR) is associated with transmission in men who have sex with men (MSM), non MSM clusters, sexually transmitted infections (STIs) and can lead to antiretroviral failure. UK guidelines recommend performing TDR testing in all newly-diagnosed people living with HIV. We audited performance of TDR in our large tertiary HIV department from 2014–2020. All new patients had TDR testing attempted in the study period. The rate of TDR was 8% and was associated with increasing age and having non-B subtype. Having non-B subtype was not associated with being non-UK born. Thirty-four percent of people were diagnosed with a bacterial STI at the time of HIV diagnosis, but STI diagnosis was not associated with TDR. There was no significant change in TDR over the 6-year audit period. TDR remains a small but significant problem. Identifying these populations and providing effective HIV prevention interventions will reduce HIV incidence and TDR.

2021 ◽  
Vol 9 ◽  
Author(s):  
Dan Yuan ◽  
Bin Yu ◽  
Yiping Li ◽  
Zixin Wang ◽  
Meijing Liu ◽  
...  

Introduction: Transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) efficacy. We aimed to understand the molecular epidemiology of TDR and its genetic transmission networks among newly diagnosed people living with HIV/AIDS (PLWH).Methods: A total of 1,318 newly diagnosed PLWH, identified in all population-based HIV screening in an HIV-affected county of a minority area of China (i.e., Butuo county), were enrolled between January 1, 2018, and November 31, 2018. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The genetic transmission networks were identified.Results: The prevalence of TDR among newly diagnosed PLWH was 8.12% (107/1,318). Patients in the stage of AIDS (adjusted odds ratio, OR: 2.32) and who had a history of sharing a needle ≥5 times (adjusted OR: 3.89) were more likely to have an increased risk of TDR. The prevalence of TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) is higher than that of other inhibitors, with a relatively high prevalence of three mutations [V179D/E/DE (4.93%), K103N/KN (3.11%), and E138A/G (1.52%)]. A total of 577 (43.78%) pol sequences were involved in the genetic transmission network, with 171 clusters ranging in size from 2 to 91 pol sequences; 37.38% (40/107) of individuals carrying TDR were involved in the network, and individuals with the same TDR-associated mutations were usually cross-linked.Conclusions: Our data suggest a relatively high level of TDR and many transmission clusters among the newly diagnosed PLWH. Targeted intervention, early identification, and monitoring of resistance are warranted to reduce the TDR and prevent HIV-1 transmission in areas with a high rate of HIV-1.


2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.


2020 ◽  
Author(s):  
Dan Yuan ◽  
Meijing Liu ◽  
Peng Jia ◽  
Yiping Li ◽  
Yuling Huang ◽  
...  

Abstract Background Liangshan Yi Autonomous Prefecture is one of the areas that most severely affected by human immunodeficiency virus (HIV) in China, and virological failure on antiretroviral therapy (ART) is serious in this area. Analyses of prevalence and determinants of ART failure, the genetic diversity and drug resistance among people living with HIV (PLWH) helps improve HIV treatment efficiency and prevent HIV transmission. Methods A total of 5157 PLWH were recruited from 2016 to 2017. The venous blood samples were subjected to RT-PCR, followed by sequencing of the HIV-1 pol gene, targeting the protease and reverse transcriptase fragments. HIV-1 diversity was analyzed using the DNAStar software and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database. Results A total of 2156 (41.81%) PLWH showed virological failure on ART. Males (ORm=1.25), heterosexual behaviors and drug injection (ORm=1.44) and mother to child transmission routes (ORm=1.58), the clinical stage of AIDS (ORm=1.35), having used illicit drugs and shared the needles (1-4 times: ORm=1.34; more than 5 times: ORm=1.52), having ever replaced ART regimen (ORm=1.48) increased the risk of virological failure among PLWH, while higher education lever (ORm=0.77) and ≥12 months on ART (12~36 months: ORm=0.72; ≥36 months: ORm=0.66) was associated with lower likelihood of virological failure. The data revealed that CRF07_BC (1508, 95.62%) were the most common strains, and the drug-resistant rate was 32.10% among PLWH with virological failure in this area. The high frequencies of drug resistance were found in EFV and NVP of NNRTIs, ABC, FTC and 3TC of NRTIs, and TPV/r in PIs. The most common mutations in NNRTIs, NRTIs and PIs were K103N/KN (64.69%), M184V/MV/I (36.29%) and Q58E/QE (4.93%), respectively. Conclusion We concluded that surveillance of virological failure, HIV-1 subtypes, and drug resistance to understand HIV-1 epidemiology and guide modification of ART guidelines, and target prevention and control strategies should be formatted to reduce the virological failure and drug resistance to promote viral suppression and prevent HIV-1 transmission.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yibo Ding ◽  
Min Chen ◽  
Jibao Wang ◽  
Yuecheng Yang ◽  
Yi Feng ◽  
...  

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianwu Pang ◽  
Hui Wei ◽  
Jinghua Huang ◽  
Qin He ◽  
Kailing Tang ◽  
...  

AbstractThe 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 ˃ 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(s):  
Hotma Martogi Lorensi Hutapea ◽  
Tri Nury Kridaningsih ◽  
Khoirul Huda Prasetyo ◽  
Milton Boaheng Antwi

Background The human immunodeficiency virus type 1 (HIV-1) is a major contagion faced by the population of Indonesia. The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). The aim of this study was to determine the association between CD4 count, CD4 count changes, viral load, adherence to therapy, and therapy history in the presence of DRM in people living with HIV/AIDS (PLWHA). MethodsThis was a cross-sectional study involving 269 adults who underwent antiretroviral (ARV) therapy for at least 6 months. The frequencies of DRM and polymorphisms were measured by partial amplification of the reverse transcriptase (RT) gene using RT-nested PCR on samples with viral loads of >1000 copies/mL. Sequencing was performed using the Sanger method, and edited by BioEdit. The edited sequences were submitted to http://hivdb.stanford.edu for DRM determination. Respondents’ medical data, CD4 count, viral load, and DRM were analyzed by simple and multiple logistic regression. ResultsThe multiple logistic regression analysis showed a significant association of CD4 count (aOR=12.47; 95% CI: 1.45 -107.39; p=0.023) and viral load at the time of study (aOR=29.56; 95% CI: 3.47-251.52; p=0.002) with the presence of DRM in respondents. ARV substitution history was not associated with the presence of DRM. There were 17 respondents (6.3%) carrying HIV-1 DRM, with M184V/I (11 sequences) as the most frequent pattern of NRTI resistance, and K103 (9 sequences) as that of NNRTI resistance. ConclusionThis study demonstrated that viral load at the time of the study was the most influential determinant factor for the presence of DRM in PLWHA.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Minna Zheng ◽  
Maohe Yu ◽  
Shaohui Cheng ◽  
Ning Zhou ◽  
Tielin Ning ◽  
...  

Abstract Background In Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of HIV cases in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. Methods Blood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support. Results Among the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Eight sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. Conclusion We revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission.


2020 ◽  
Author(s):  
Dan Yuan ◽  
Meijing Liu ◽  
Peng Jia ◽  
Yiping Li ◽  
Yuling Huang ◽  
...  

Abstract Background: Liangshan Yi Autonomous Prefecture is one of the areas that most severely affected by human immunodeficiency virus (HIV) in China, and virological failure on antiretroviral therapy (ART) is serious in this area. Analyses of prevalence and determinants of ART failure, the genetic diversity and drug resistance among people living with HIV (PLWH) helps improve HIV treatment efficiency and prevent HIV transmission.Methods: A total of 5157 PLWH were recruited from 2016 to 2017. The venous blood samples were subjected to RT-PCR, followed by sequencing of the HIV-1 pol gene, targeting the protease and reverse transcriptase fragments. HIV-1 diversity was analyzed using the DNAStar software and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database.Results: A total of 2156 (41.81%) PLWH showed virological failure on ART. Males (ORm=1.25), heterosexual behaviors and drug injection (ORm=1.44) and mother to child transmission routes (ORm=1.58), the clinical stage of AIDS (ORm=1.35), having used illicit drugs and shared the needles (1-4 times: ORm=1.34; more than 5 times: ORm=1.52), having ever replaced ART regimen (ORm=1.48) increased the risk of virological failure among PLWH, while higher education lever (ORm=0.77) and ≥12 months on ART (12~36 months: ORm=0.72; ≥36 months: ORm=0.66) was associated with lower likelihood of virological failure. The data revealed that CRF07_BC (1508, 95.62%) were the most common strains, and the drug-resistant rate was 32.10% among PLWH with virological failure in this area. The high frequencies of drug resistance were found in EFV and NVP of NNRTIs, ABC, FTC and 3TC of NRTIs, and TPV/r in PIs. The most common mutations in NNRTIs, NRTIs and PIs were K103N/KN (64.69%), M184V/MV/I (36.29%) and Q58E/QE (4.93%), respectively.Conclusion: We concluded that surveillance of virological failure, HIV-1 subtypes, and drug resistance to understand HIV-1 epidemiology and guide modification of ART guidelines, and target prevention and control strategies should be formatted to reduce the virological failure and drug resistance to promote viral suppression and prevent HIV-1 transmission.


2020 ◽  
Author(s):  
Minna Zheng ◽  
Maohe Yu ◽  
Shaohui Chen ◽  
Ning Zhou ◽  
Tielin Ning ◽  
...  

Abstract BackgroundIn Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of cases of HIV in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. MethodsBlood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support.ResultsAmong the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Nine sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. ConclusionWe revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S195-S196
Author(s):  
Christine Convery ◽  
James B Kent

Abstract Background Sexually transmitted infections (STIs) have increased in recent years both nationally and in Michigan. At the same time, HIV prevention is shifting toward intense efforts to “ending the epidemic.” Detecting and mitigating outbreaks, as well as monitoring co-infections in people living with HIV (PLWH), will be critical in these efforts. Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by a serovar of Chlamydia trachomatis and may present with proctitis, lymphadenopathy, or genital ulcers. Methods While not nationally reportable, LGV remains on the list of reportable conditions in Michigan. No cases were reported between 2009 and 2014, but from August 12, 2015 to December 4, 2018, 68 cases of LGV were identified in 66 patients and reported by providers and laboratories through the Michigan Disease Surveillance System (MDSS). These reported cases were analyzed by specimen collection date and matched to other communicable disease databases for HIV co-infection status and STI history using SAS 9.4. Results The outbreak was local to Southeast Michigan where all but three patients resided; 72% cases lived in Detroit (Figure 1). 94% of cases were co-infected with HIV, including 4 who were co-diagnosed within 30 days of LGV diagnosis. Among the 60 cases of PLWH (excluding co-diagnoses), 62% were virally suppressed (VS) and 32% were in care but not suppressed at the time of LGV diagnosis. The majority (88%) of outbreak patients had between 1 and 7 additional bacterial STIs in the two years prior to LGV. All reported cases were men who have sex with men (MSM) with two patients also reporting injection drug use (MSM/IDU). Conclusion Testing for LGV is not routine and in some settings not available so there are likely unreported cases missing from this outbreak analysis. HIV care outcomes differed from statewide estimates with outbreak patients more likely to be receiving care but not sufficiently engaged compared with all PLWH (Figure 2). A high proportion of cases with additional STI history combined with lower than average VS rate means transmission of HIV is likely. This highlights a need to integrate HIV care support with STI services. Additional analyses of HIV co-infection with syphilis or other STIs are needed to further inform these strategies. Disclosures All authors: No reported disclosures.


Sign in / Sign up

Export Citation Format

Share Document