Prevalence Of Transmitted Drug Resistance Research Articles

Prevalence of transmitted drug resistance and phylogenetic analysis of HIV-1 among antiretroviral therapy-naïve patients in Northern Vietnam from 2019 to 2022.

Since the rapid expansion of antiretroviral therapy (ART) for HIV, transmitted drug resistance (TDR) has become a major concern in Vietnam. HIV services there are transitioning to be covered by social insurance. Access to pre-exposure prophylaxis (PrEP) is being expanded to tackle the growing HIV epidemic among men who have sex with men. Therefore, a cross-sectional study was conducted at 10 ART facilities in Northern Vietnam from 9th December 2019 to 9th June 2022 to investigate the prevalence and pattern of TDR among ART-naïve people living with HIV (PLWH). TDR mutations were defined according to the World Health Organization 2009 List of Mutations for Surveillance of Transmitted Drug Resistant HIV Strains. Mutation transmission dynamics and TDR clusters were investigated via phylogenetic analysis. We enrolled 391 ART-naïve PLWH. The overall TDR prevalence was 4.6%, with an annual prevalence of 6.0% in 2019/2020, 4.8% in 2021, and 1.3% in 2022. TDR mutations to non-nucleoside reverse transcriptase inhibitors (2.8%), including K103N were the most common. Less commonly, the protease inhibitor-associated mutation M46I and mutations to nucleoside reverse transcriptase inhibitors, including M184V/ I, were observed. CRF01_AE was the most common subtype (77.0%). CRF07_BC (14.3%), which had been rare in Vietnam, was also observed. No genetic association was observed between HIV-1 sequences with TDR mutations. In conclusion, the overall prevalence of TDR was stably low in this region. The phylogenetic tree suggests that TDR clusters have not formed. Continuous monitoring of HIV TDR and strains is crucial to maintaining ART and PrEP efficacy.

Applying Next-Generation Sequencing to Track HIV-1 Drug Resistance Mutations Circulating in Portugal.

The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission. We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal. Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay. About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs. We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir).

Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022.

Molecular epidemiology of HIV-1 infection is challenging due to the highly diverse HIV-genome. We investigated the genetic diversity and prevalence of transmitted drug resistance (TDR) followed by phylogenetic analysis in 270 HIV-1 infected, treatment-naïve individuals from Croatia in the period 2019-2022. The results of this research confirmed a high overall prevalence of TDR of 16.7%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PIs) was found in 9.6%, 7.4%, and 1.5% of persons, respectively. No resistance to integrase strand-transfer inhibitors (INSTIs) was found. Phylogenetic analysis revealed that 173/229 sequences (75.5%) were part of transmission clusters, and the largest identified was T215S, consisting of 45 sequences. Forward transmission was confirmed in several clusters. We compared deep sequencing (DS) with Sanger sequencing (SS) on 60 randomly selected samples and identified additional surveillance drug resistance mutations (SDRMs) in 49 of them. Our data highlight the need for baseline resistance testing in treatment-naïve persons. Although no major INSTIs were found, monitoring of SDRMs to INSTIs should be continued due to the extensive use of first- and second-generation INSTIs.

HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021

BackgroundAs the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions.MethodsConsecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013.ResultsA total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021.ConclusionsThis study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.

HIV-1 molecular transmission network and drug resistance in Chongqing, China, among men who have sex with men (2018–2021)

BackgroundOver the past few years, HIV transmission among men who have sex with men (MSM) in China has increased significantly. Chongqing, located in the southwest of China, has the highest prevalence of HIV among MSM in the country.MethodsBlood samples were taken from 894 MSM in Chongqing who had recently been diagnosed with HIV-1 infection and had not yet started getting treatment. In order to determine the distribution of HIV-1 subtypes, transmitted drug resistance, and assessments of molecularly transmitted clusters, we sequenced the Pol genes and employed them in phylogenetic analysis. The genetic distance between molecular clusters was 1.5%. To find potential contributing factors, logistic regression analyses were performed.ResultsOf the 894 HIV-1 pol sequences acquired from study participants, we discovered that CRF07_BC (73.6%) and CRF01_AE (19.6%) were the two most prevalent HIV-1 genotypes in Chongqing among MSM, accounting for 93.2% of all infections. In addition, CRF08_BC (1.1%), B subtype (1.0%), CRF55_01B (3.4%), and URF/Other subtypes (1.3%) were less frequently observed. Among MSM in Chongqing, transmitted drug resistance (TDR) was reported to be present at a rate of 5.6%. 48 clusters with 600 (67.1%, 600/894) sequences were found by analysis of the molecular transmission network. The distributions of people by age, sexual orientation, syphilis, and genotype were significantly differentially related to being in clusters, according to the multivariable logistic regression model.ConclusionDespite the low overall prevalence of TDR, the significance of genotypic drug resistance monitoring needs to be emphasized. CRF07_BC and CRF01_AE were the two main genotypes that created intricate molecular transmission networks. In order to prevent the expansion of molecular networks and stop the virus’s spread among MSM in Chongqing, more effective HIV intervention plans should be introduced.

Modelling the impact of treatment adherence on the transmission of HIV drug resistance.

A lower adherence rate (percentage of individuals taking drugs as prescribed) to ART may increase the risk of emergence and transmission of HIV drug resistance, decrease treatment efficacy, and increase mortality rate. Exploring the impact of ART adherence on the transmission of drug resistance could provide insights in controlling the HIV epidemic. We proposed a dynamic transmission model incorporating the CD4 cell count-dependent rates of diagnosis, treatment and adherence with transmitted drug resistance (TDR) and acquired drug resistance. This model was calibrated and validated by 2008-2018 HIV/AIDS surveillance data and prevalence of TDR among newly diagnosed treatment-naive individuals from Guangxi, China, respectively. We aimed to identify the impact of adherence on drug resistance and deaths during expanding ART. In the base case (ART at 90% adherence and 79% coverage), we projected the cumulative total new infections, new drug-resistant infections, and HIV-related deaths between 2022 and 2050 would be 420 539, 34 751 and 321 671. Increasing coverage to 95% would reduce the above total new infections (deaths) by 18.85% (15.75%). Reducing adherence to below 57.08% (40.84%) would offset these benefits of increasing coverage to 95% in reducing infections (deaths). Every 10% decrease in adherence would need 5.07% (3.62%) increase in coverage to avoid an increase in infections (deaths). Increasing coverage to 95% with 90% (80%) adherence would increase the above drug-resistant infections by 11.66% (32.98%). A decrease in adherence might offset the benefits of ART expansion and exacerbate the transmission of drug resistance. Ensuring treated patients' adherence might be as important as expanding ART to untreated individuals.

Increased prevalence and stable clustering rate of HIV-1 transmitted drug resistance strains after 'treat-all' in a megacity of China.

The 'treat-all' strategy was implemented in Shenzhen, China in 2016. The effect of this extensive treatment on transmitted drug resistance (TDR) of HIV is unclear. TDR analysis was performed, based on the partial HIV-1 pol gene obtained from the newly reported HIV-1 positive cases from 2011 to 2019 in Shenzhen, China. The HIV-1 molecular transmission networks were inferred to analyse the spread of TDR. Logistic regression was used to identify the potential risk factors with TDR mutations (TDRMs) to cluster. A total of 12 320 partial pol sequences were included in this study. The prevalence of TDR was 2.95% (363/12 320), which increased from 2.57% to 3.52% after 'treat-all'. The TDR prevalence was increased in populations with the characteristics of CRF07_BC, being single, educated to junior college level and above, MSM and male. The sensitivities of viruses to six antiretroviral drugs were decreased. The clustering rate of TDRMs remained stable, and the sequences in the three drug resistance transmission clusters (DRTCs) were mainly found during 2011-16. CRF07_BC and CRF55_01B were the factors associated with TDRMs clustering in the networks. The 'treat-all' strategy might have contributed to a small increase in TDR, while most of the TDRMs were distributed sporadically, which implies that the 'treat-all' strategy is helpful for the control of TDR in high-risk populations.

Prevalence of HIV Transmitted Drug Resistance in Nanjing from 2018 to 2021.

Transmitted drug resistance (TDR) is a major challenge in the clinical management of acquired immunodeficiency syndrome (AIDS). Therefore, this study aimed to investigate the epidemic characteristics of and risk factors for human immunodeficiency virus (HIV)-1 TDR in Nanjing from 2018 to 2021 to provide support for clinical management. The HIV-1 Pol gene was amplified by nested reverse transcription polymerase chain reaction from venous blood of 1190 HIV-infected patients who did not receive antiviral therapy, and the amplified product was sequenced using an in-house sequencing method. The sequencing result was compared with the HIV drug resistance database from Stanford University to elucidate the rates of antiviral drug resistance and distribution of drug-resistant mutation sites. Factors associated with TDR were evaluated using a logistic regression model. Detection of drug resistance at the gene level was successful in 1138 of 1190 HIV-1-infected patients (95.6%), and the overall 4-year drug resistance rate was 8.2% (93/1138). The drug resistance rate was higher for non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.7%) than for nucleoside reverse transcriptase inhibitors (NRTIs; 2.5%) or protease inhibitors (PIs; 0.1%) (χ 2 = 83.907, P<0.0001). The most common NNRTI-related mutation was V179D/E followed by K103N. M184V was the dominant NRTI-associated mutation, and M46L/I was the most prevalent PI-associated mutation. A CD4+ T cell count of <50 cells/μL was significantly associated with an increased risk of TDR (OR=3.62, 95% CI: 1.38-9.51, P=0.009). The prevalence of TDR in the city of Nanjing from 2018 to 2021 was at a moderate epidemic risk according to World Health Organization standards. Continuous monitoring of TDR can inform clinical diagnosis and treatment. Patients with advanced disease and a low CD4+ T lymphocyte count are more likely to have TDR in Nanjing.

Transmitted drug resistance and transmission clusters among ART-naïve HIV-1-infected individuals from 2019 to 2021 in Nanjing, China.

Transmitted drug resistance (TDR) is an increasingly prevalent problem worldwide, which will significantly compromise the effectiveness of HIV treatments. However, in Nanjing, China, there is still a dearth of research on the prevalence and transmission of TDR among ART-naïve HIV-1-infected individuals. This study aimed to understand the prevalence and transmission of TDR in Nanjing. A total of 1,393 participants who were newly diagnosed with HIV-1 and had not received ART between January 2019 and December 2021 were enrolled in this study. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR amplification. Genotypes, TDR and transmission cluster analyses were conducted using phylogenetic tree, Stanford HIV database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with TDR. A total of 1,161 sequences were successfully sequenced, of which CRF07_BC (40.6%), CRF01_AE (38.4%) and CRF105_0107 (6.3%) were the main HIV-1 genotypes. The overall prevalence of TDR was 7.8%, with 2.0% to PIs, 1.0% to NRTIs, and 4.8% to NNRTIs. No sequence showed double-class resistance. Multivariate logistic regression analysis revealed that compared with CRF01_AE, subtype B (OR = 2.869, 95%CI: 1.093-7.420) and female (OR = 2.359, 95%CI: 1.182-4.707) were risk factors for TDR. Q58E was the most prevalent detected protease inhibitor (PI) -associated mutation, and V179E was the most frequently detected non-nucleoside reverse transcriptase inhibitor (NNRTI) -associated mutation. A total of 613 (52.8%) sequences were segregated into 137 clusters, ranging from 2 to 74 sequences. Among 44 individuals with TDR (48.4%) within 21 clusters, K103N/KN was the most frequent TDR-associated mutation (31.8%), followed by Q58E/QE (20.5%) and G190A (15.9%). Individuals with the same TDR-associated mutations were usually cross-linked in transmission clusters. Moreover, we identified 9 clusters in which there was a transmission relationship between drug-resistant individuals, and 4 clusters in which drug-resistant cases increased during the study period. The overall prevalence of TDR in Nanjing was at a moderate level during the past 3 years. However, nearly half of TDR individuals were included in the transmission clusters, and some drug-resistant individuals have transmitted in the clusters. Therefore, HIV drug-resistance prevention, monitoring and response efforts should be sustained and expanded to reduce the prevalence and transmission of TDR in Nanjing.

Changes in HIV-1 Subtypes/Sub-Subtypes, and Transmitted Drug Resistance Among ART-Naïve HIV-Infected Individuals - China, 2004-2022.

The efficacy of treatment and clinical outcomes may be jeopardized by factors such as transmitted drug resistance (TDR) and the genetic diversity of the human immunodeficiency virus type 1 (HIV-1). This comprehensive study aims to examine the alterations in HIV-1 subtypes or sub-subtypes and TDR among Chinese individuals, who have been diagnosed with HIV infection and are previously untreated with antiretroviral therapy (ART), across the span of 2004 to 2022. Sequences of the HIV-1 pol gene region were obtained from ART-naïve HIV-positive individuals across 31 provincial-level administrative divisions between 2004 and 2022. To predict susceptibility to 12 antiretroviral drugs, the research utilized the Stanford HIV Drug Resistance Database. The Cochran-Armitage trend test facilitated the analysis of changes in HIV-1 subtype/sub-subtype prevalence and TDR. This analysis was conducted in alignment with the progression of the National Free Antiretroviral Treatment Program's stages between 2004 and 2022. Among the 57,902 ART-naïve individuals infected with HIV, there was a notable decline in the prevalence of CRF01_AE, B, and C from 37.3%, 24.1%, and 1.3% respectively in 2004-2007 to 29.4%, 7.3%, and 0.2% respectively in 2020-2022. Simultaneously, a significant increase was observed in the proportions of CRF07_BC, CRF08_BC, CRF55_01B, other CRFs, and URFs, from 24.1%, 11.5%, 0.1%, 0.4%, and 0.9% respectively in 2004-2007 to 40.8%, 11.5%, 3.8%, 3.7%, and 2.8% respectively in 2020-2022 (all P<0.001 for trend). The prevalence of TDR to overall, non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, and nevirapine also significantly increased from 2.6%, 1.8%, 1.6%, and 1.8% respectively in 2004-2007 to 7.8%, 6.7%, 6.3%, and 6.7% respectively in 2020-2022 (all P<0.001 for trend). However, there were no meaningful changes in the TDR prevalence of nucleoside reverse transcriptase inhibitor and protease inhibitor. Notably, in 2020-2022, the overall TDR prevalence exceeded 15% in Xinjiang. The total prevalence of TDR in China has achieved a moderate level (7.8%) from 2020 to 2022, with NNRTI resistance standing prominently at 6.7%. Consequently, measures to curb TDR are urgently required, particularly among ART-naïve HIV-infected individuals in China.

Low Prevalence of Transmitted HIV-1 Antiretroviral Resistance in Pregnant Women from Rio de Janeiro, Brazil

Background: HIV screening during antenatal care is being expanded in Brazil for early diagnosis of HIV-1 infection during pregnancy and prevention of vertical transmission. HIV genotyping in pregnant women is crucial to reduce the risk of vertical transmission in those carrying resistant strains and may also be used for Transmitted Drug Resistance (TDR) surveillance purpose. We evaluated prevalence and patterns of HIV-1 TDR and HIV subtype distribution in recently diagnosed ARV naïve pregnant women from Rio de Janeiro, Brazil. Methods: 299 blood samples of recently diagnosed HIV-1-infected pregnant women from four reference antenatal care public health units in Rio de Janeiro were consecutively collected and analyzed from 2005 to 2015.ViroseqTM (Abbott) and TrugeneTM HIV-1 Genotyping Systems (Siemens) were used for genotyping and the Standford Algorithm for Interpretation of HIV-1 Resistance for TDR and subtype identification. Results: The most prevalent HIV-1 subtype was the subtype B (77%), followed by subtype F (15%), BF recombinant forms (4%), subtype C (2%) and the recombinant forms: CRF02_AG, CRF31_BC and DF identified in one subject each. Overall, the TDR mutations was 11.7%, 2.7% associated to the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) of the samples, 2.7% to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and 1% to Protease Inhibitors (PIs). Mutations associated with NRTI resistance were TAMs, F77L, M184V; associated with NNRTI resistance were K103N, Y188H and L100I and. mutations associated to PIs were D30N, M46I, and V82L. Conclusions: HIV-1 subtype B was the most prevalent subtype observed in our study. For the first time infections with the circulating recombinant forms CRF02_AG and CRF31_BC were described in a pregnant woman, suggesting the spread of African derived virus in Brazil and the introduction in Rio de Janeiro of the CRF31_BC coming from South Brazil. Our results strongly suggest the need of establishing a regular surveillance system for transmitted HIV-1 drug resistance in pregnant women in Brazil and its integration in antenatal care management policies for HIV-1 infected women should be considered.

Trend of HIV Transmitted Drug Resistance After the Introduction of Single-Tablet Regimens in Southern Taiwan.

BackgroundThe prevalence of transmitted drug resistance (TDR) after the universal implementation of STRs is unknown in Taiwan.ObjectiveThis study aimed to investigate the prevalence of TDR in patients with HIV-1 infection, clarify the risk factors for pol resistance, and compare differences in HIV drug resistance before and after the implementation of STRs in Taiwan.MethodsAdult patients infected with HIV-1 were enrolled in this study from 2013 to 2021. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database edition 9. A logistic regression model was used to analyze the risk factors for pol resistance, and the differences in the prevalence of drug resistance from 2013–2016 to 2017–2021 were compared using the Mann–Whitney U-test. General linear regression was used to analyze temporal changes in the annual proportion of TDR overall and by type of antiretroviral drugs.ResultsA total of 369 patients were included. The prevalence rate of pol resistance was 9.8% (36/369). The resistance rates to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 3.3%, 6.9%, 0% and 1.8%, respectively. The patients with hepatitis C infection were more likely to have pol resistance (aHR 5.767, CI 1.232–26.991, p=0.026). The prevalence rate of pol resistance did not decrease after the implementation of STRs as first-line therapy in 2017 (11.2% vs 8.7%, aHR 1.329, CI 0.667–2.645, p=0.480), and no significant temporal changes were shown in the annual proportion of TDR overall or by type of antiretroviral drug.ConclusionOur findings showed a stable prevalence rate of transmitted drug resistance despite the implementation of STRs as the first-line therapy in June 2016.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks.MethodsClinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses.ResultsIn Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G.ConclusionOur molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters.

BackgroundThe increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.ObjectiveTo describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.MethodsOur study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019.ResultsAmong the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0–45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend < 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend < 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M.ConclusionOur study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.

Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019.

BackgroundTo assess the prevalence and evolution of transmitted drug resistance (TDR) in Belgium, a total of 3708 baseline human immunodeficiency virus (HIV)-1 polymerase sequences from patients diagnosed between 2013 and 2019 were analyzed.MethodsProtease and reverse-transcriptase HIV-1 sequences were collected from the 7 national Aids Reference Laboratories. Subtype determination and drug resistance scoring were performed using the Stanford HIV Drug Resistance Database. Trends over time were assessed using linear regression, and the maximum likelihood approach was used for phylogenetic analysis.ResultsA total of 17.9% of the patients showed evidence of TDR resulting in at least low-level resistance to 1 drug (Stanford score ≥15). If only the high-level mutations (Stanford score ≥60) were considered, TDR prevalence dropped to 6.3%. The majority of observed resistance mutations impacted the sensitivity for nonnucleoside reverse-transcriptase inhibitors (NNRTIs) (11.4%), followed by nucleoside reverse-transcriptase inhibitors (6.2%) and protease inhibitors (2.4%). Multiclass resistance was observed in 2.4%. Clustered onward transmission was evidenced for 257 of 635 patients (40.5%), spread over 25 phylogenetic clusters.ConclusionsThe TDR prevalence remained stable between 2013 and 2019 and is comparable to the prevalence in other Western European countries. The high frequency of NNRTI mutations requires special attention and follow-up. Phylogenetic analysis provided evidence for local clustered onward transmission of some frequently detected mutations.

Prevalence of HIV-1 transmitted drug resistance and its impact on the effectiveness of antiretroviral therapy - Minas Gerais state, Brazil / Prevalência de resistência transmitida do HIV-1 e seu impacto na efetividade da terapia antirretroviral – Minas Gerais, Brasil

The transmission and occurrence of resistance associated mutations (RAMs) are among the challenges for a successful HIV Treatment. Therefore, continuous HIV drug resistance surveillance of prevalence and incidence is recommended. The objective this study was to analyze the prevalence and impact of transmitted drug resistance (TDR) on the first-line ART effectiveness. This is a retrospective observational study that evaluated HIV-1-infected treatment-naïve individuals with pre-antiretroviral therapy (ART) genotype resistance test results, between 2014 and 2015, in Minas Gerais state’s, Brazil. The ART effectiveness was compared in individual with and without TDR, considering viral load (VL) 50 copies/mL at the 12 and 24-month endpoint. Reverse transcriptase and protease sequences were genotyped by Sanger sequencing. A total of 170 individuals were selected. HIV-1 subtype B was highly prevalent (63.5%) and prevalence of TDR was 14.1%. That included 62.5% RAMs associated with non-nucleoside reverse-transcriptase inhibitors (NNRTIs), 29.2% with nucleos(t)ide transcriptase inhibitors (NRTIs) and 25% with protease inhibitors (PIs). The overall ART effectiveness measured at 12 and 24 months was, respectively: 91.0% and 93.4% between individuals without TDR; 88.2% and 93.3% in individuals with TDR. Among the individuals starting first-line ART with less than three active drugs (16/24), seven individuals achieved VL 50 copies/mL in the presence of K103N mutation and receiving efavirenz-containing ART. Moderate prevalence of TDR was observed in this study, although observed that some NNRTI TDR, did not impact on the effectiveness of efavirenz-based regimens, without major differences on the effectiveness of first-line ART between the groups with or without TDR.

Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China.

Since the implementation of the “treat all” policy in China in 2016, there have been few data on the prevalence of transmitted drug resistance (TDR) in China. In this study, we describe TDR in patients newly diagnosed with human immunodeficiency virus (HIV) infection between 2016 and 2019 in Shenyang city, China. Demographic information and plasma samples from all newly reported HIV-infected individuals in Shenyang from 2016 to 2019 were collected. The HIV pol gene was amplified and sequenced for subtyping and TDR. The spread of TDR was analyzed by inferring an HIV molecular network based on pairwise genetic distance. In total, 2,882 sequences including CRF01_AE (2019/2,882, 70.0%), CRF07_BC (526/2,882, 18.3%), subtype B (132/2,882, 4.6%), and other subtypes (205/2,882, 7.1%) were obtained. The overall prevalence of TDR was 9.1% [95% confidence interval (CI): 8.1–10.2%]; the prevalence of TDR in each subtype in descending order was CRF07_BC [14.6% (95% CI: 11.7–18.0%)], subtype B [9.1% (95% CI: 4.8–15.3%)], CRF01_AE [7.9% (95% CI: 6.7–9.1%)], and other sequences [7.3% (95% CI: 4.2–11.8%)]. TDR mutations detected in more than 10 cases were Q58E (n = 51), M46ILV (n = 46), K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12). Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. In the TDR clusters, 96.4% (53/55) of individuals were men who have sex with men (MSM). These results indicate that TDR is moderately prevalent in Shenyang (5–15%) and that TDR strains are mainly transmitted among MSM, providing precise targets for interventions in China.

Transmitted HIV-1 Drug-resistance Mutations among Newly Diagnosed Patients of the North Western Region of Cameroon

Background: First line antiretroviral treatment (ART) regimens in Cameroon comprises of reverse transcriptase inhibitors (RTIs). As ART continues to expand, the emergence of HIV drug resistance mutations (DRMs) is a challenging problem. The ongoing scale up of ART in Cameroon has prompted the interest in surveillance of transmitted drug resistance (TDR). The aim of this study was to evaluate the prevalence of TDR among drug naïve individuals residing in the North West Region (NWR) of Cameroon.&#x0D; Methods: Ethics approval was obtained from the National Ethics Committee of Cameroon and patients informed consents were obtained. A total of 81 HIV-1 infected and drug naïve patients were recruited from randomly selected clinics located in the NWR of Cameroon from February 2016 and April 2016. HIV-1 protease-reverse transcriptase region was sequenced using an in-house protocol. HIV drug resistance mutations were identified and analyzed using Stanford HIVDR database and the Calibrated Population Resistance (CPR) tools. Data was analyzed using SPSS version 23.&#x0D; Results: Of the 81 samples analyzed, the prevalence of TDR was 11.1% (9/81). Of these 9.9% (8/81) had drug resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) and a single individual (1.2%) with protease inhibitors. A total of 8.6 % (7/81), 4.9(4/81), and 3.7 % (3/81) individuals had a major mutation to NRTIs, NNRTIs, and both NRTIs and NNRTIs respectively. Thymidine analogue mutations [TAM] (M41ML, D67N, K70T/R, T215TA/F, and K219Q) were detected in five individuals. The most frequent NRTI and NNRTI DRMs were K219Q (n=2) and E138A (n=2) respectively. Mutations associated with NRTIs were TAM and M184MV; NNRTIs were A98G, K103N, V108I, V179E, and Y181C and I54IFV for PI. CPR tool revealed a 4.9% (4/81) prevalence with the following single mutations K103N D67N, K70R, M184V, T215F, K219Q.The difference between two methods was statistically significant p=0.0001. These mutations confer resistance to all NRTIs and NNRTIs drugs.&#x0D; Conclusions: Although moderate transmitted drug resistance (11.1%) levels were detected in this study, this calls for routine drug resistance surveillance among patients on ART. This will ensure relative maintenance of low viral suppression amongst HIV patients.

Transmitted Drug Resistance in Antiretroviral Therapy-Naive Persons With Acute/Early/Primary HIV Infection: A Systematic Review and Meta-Analysis.

Background: The widespread use of antiretroviral therapy (ART) has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with primary HIV infection (PHI)/AHI/early HIV infection (EHI) and to describe the critical drug-resistant mutations. Methods: We systematically searched the literature between January 1, 2008, and April 30, 2021, in PubMed, Web of Science, Embase, and the Cochrane Library. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE. Results: The data of this meta-analysis come from 12 observational studies, covering 3,558 ART-naive individuals with PHI, AHI, or EHI. The overall prevalence of HIV-TDR is 9.3% (95% CI: 6.8%–11.8%, I2 = 81.1%, in 11 studies). The prevalence of resistance by drug class is the highest for the nonnucleoside reverse transcriptase inhibitors (NNRTIs) at 5.7% (95% CI: 2.9%–8.5%, I2 = 96.6%, in 11 studies), followed by nucleoside reverse transcriptase inhibitors (NRTIs) at 3.4% (95% CI: 1.8%–5.0%, I2 = 86.3%, in 10 studies) and protease inhibitors (PIs) at 3.3% (95% CI: 2.7%–3.9%, I2 = 15.6%, in 10 studies). The prevalence of TDR to integrase inhibitors (INIs) is 0.3% (95% CI: 0.1%–0.7%, I2 = 95.9%, in three studies), which is the lowest among all antiretroviral drugs. Conclusion: The overall prevalence of TDR is at a moderate level among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.

High prevalence of HIV-1 transmitted drug resistance and factors associated with time to virological failure and viral suppression in Taiwan.

Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan. To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan. The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression. The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes. This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression.