Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China.
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ABSTRACT: Introduction
Pretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics.Methods
Plasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined.Results
A total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2-143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing.Conclusion
PDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.
SUBMITTER: Zhang F
PROVIDER: S-EPMC8460771 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014-2020 in southwestern China.MethodsConsecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014-2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR.ResultsIn total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p < 0.001) and PI (1.2%, p < 0.001). A multivariate logistic regression analysis revealed that PDR was significantly higher among individuals aged 18-29 (adjusted odds ratio (aOR): 1.79, 95% CI 1.28-2.50) or 30-49 (aOR: 2.82, 95% CI 1.73-4.82), and harboring CRF08_BC (aOR: 3.23, 95% CI 1.58-6.59). A total of 1429 (43.8%) sequences were linked forming transmission clusters ranging in size from 2 to 119 individuals. Twenty-two individuals in 10 clusters had the same drug resistant mutations (DRMs), mostly to NNRTIs (50%, 5/10).ConclusionsThe overall prevalence of PDR was medium, numerous cases of the same DRMs among genetically linked individuals in networks further illustrated the importance of surveillance studies for mitigating PDR.
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Project description:BackgroundHIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu'er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance.MethodsA cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu'er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm.ResultsA total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM.ConclusionThe overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.
| S-EPMC9483295 | biostudies-literature
Project description:Abstract Background The prevalence of human immunodeficiency type 1 (HIV-1) pretreatment drug resistance (PDR) in men who have sex with men (MSM) in Guangxi remains unclear, and its effect on antiretroviral therapy (ART) needs to be further studied. Methods Individuals newly diagnosed with HIV in Guangxi from 2016 to 2020, which mainly included MSM and the heterosexual (HES) population, were recruited in this study. Pol sequences were sequenced to analyze PDR and construct a genetic network. The risk factors for PDR and the effect on ART were respectively analyzed. Results The PDR of MSM in Guangxi was 4.7% (34/716), consisting of nonnucleoside reverse transcriptase inhibitors (3.5%), protease inhibitors (0.8%), integrase strand transfer inhibitors (0.7%), and nucleoside reverse transcriptase inhibitors (0.4%), and lower than that of HES (9.3% [77/827]). The subtype was associated with PDR, and MSM was lower than HES (CRF01_AE: 3.0% vs 8.0%; CRF07_BC: 4.1% vs 7.2%). CRF55_01B (adjusted odds ratio [aOR], 3.35) was a risk factor for PDR in MSM, while CRF08_BC (aOR, 2.34) and older (aOR, 2.75) were risk factors for PDR in HES. Six of 18 (33.3%) PDR of MSM in the network connected to each other, lower than that of HES (61.1% [22/36]). CRF55_01B (aOR, 5.69) was a risk factor for PDR transmission in MSM, while CRF08_BC (aOR, 4.08) was a risk factor in HES. Pretreatment CD4+ T-cell count, age, infection route, and subtype were associated with recovery of CD4+ count and suppression of viral load. Conclusions The prevalence of PDR was different between MSM and HES, which may be associated with subtype. Thus, the monitoring of subtype and PDR should be strengthened.
| S-EPMC9898876 | biostudies-literature
Project description:BACKGROUND:Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. OBJECTIVES:To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. PATIENTS AND METHODS:HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (?20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a???2% threshold to include low-frequency variants. RESULTS:Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P?<?0.001). Clustering individuals were younger [adjusted OR (aOR) per year?=?0.96, 95% CI 0.95-0.97, P?<?0.001] and less likely to include women (aOR?=?0.46, 95% CI 0.28-0.75, P?=?0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR?=?0.93, 95% CI 0.88-0.98, P?=?0.003). CONCLUSIONS:Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.
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Project description:BackgroundEmerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings.ObjectiveWe aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022.MethodsThis cross-sectional study was conducted using 2-stage systematic sampling according to the World Health Organization's surveillance guidelines in 8 provincial-level administrative divisions in 2022. Demographic information and plasma samples were obtained from study participants. PDR was analyzed using the Stanford HIV drug resistance database, and the Tamura-Nei 93 model in HIV-TRACE was used to calculate pairwise matches with a genetic distance of 0.01 substitutions per site. Logistic regression was used to identify and estimate factors associated with PDR.ResultsPDR testing was conducted on 2568 participants in 2022. Of the participants, 34.8% (n=893) were aged 30-49 years, 81.4% (n=2091) were male, and 3.2% (n=81) had prior ARV exposure. The prevalence of PDR to protease and reverse transcriptase regions, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 7.4% (n=190), 6.3% (n=163), 1.2% (n=32), and 0.2% (n=5), respectively. Yunnan, Jilin, and Zhejiang had much higher PDR incidence than did Sichuan. The prevalence of nonnucleoside reverse transcriptase inhibitor-related drug resistance was 6.1% (n=157) for efavirenz and 6.3% (n=163) for nevirapine. Multivariable logistic regression models indicated that participants who had prior ARV exposure (odds ratio [OR] 7.45, 95% CI 4.50-12.34) and the CRF55_01B HIV subtype (OR 2.61, 95% CI 1.41-4.83) were significantly associated with PDR. Among 618 (24.2%) sequences (nodes) associated with 253 molecular transmission clusters (size range 2-13), drug resistance mutation sites included K103, E138, V179, P225, V106, V108, L210, T215, P225, K238, and A98.ConclusionsThe overall prevalence of PDR in China in 2022 was modest. Targeted genotypic PDR testing and medication compliance interventions must be urgently expanded to address PDR among newly diagnosed people living with HIV in China.
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Project description:HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (?10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.
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Project description:HIV-1 CRF08_BC has become a major epidemic in heterosexuals and intravenous drug users (IDUs) in southern China. In order to evaluate the trends of its epidemic and facilitate targeted HIV prevention, we constructed the genetic transmission networks based on its pol sequences, derived from the National HIV Molecular Epidemiology Survey. Through retrospective network analysis, to study the epidemiological and demographic correlations with the transmission network. Of the 1,829 study subjects, 639 (34.9%) were clustered in 151 transmission networks. Factors associated with increased clustering include IDUs, heterosexual men, young adults and people with lower education (P < 0.05 for all). The IDUs, MSM, young adult and person with low education had more potential transmission links as well (P < 0.05 for all). The most crossover links were found between heterosexual women and IDUs, with 30.9% heterosexual women linked to IDUs. The crossover links heterosexual women were mainly those with middle age and single (P < 0.001). This study indicated that the HIV-1 CRF08_BC epidemic was still on going in China with more than one third of the infected people clustered in the transmission networks. Meanwhile, the study could help identify the active CRF08_BC spreader in the local community and greatly facilitate précising AIDS prevention with targeted intervention.
| S-EPMC7993390 | biostudies-literature
Project description:BackgroundHuman immunodeficiency virus type 1 (HIV-1) genetic diversity and pre-treatment drug resistance (PDR) are major barriers to successful antiretroviral therapy (ART). In China, sexual intercourse is the most frequent route of HIV-1 transmission. However, few studies have analyzed PDR and transmission networks in detail among individuals in China with acute HIV-1 infection and their sexual contacts.MethodsA cross-sectional study was conducted in Baoding City, Hebei Province, China from 2019-2020. CD4 T cell counts and viral loads were assessed and a HIV-1 genotypic PDR assay was developed in-house. Transmission networks were visualized using Cytoscape with a threshold genetic distance of 0.015 among HIV-1 subtypes.ResultsFrom 139 newly diagnosed and drug-naïve individuals with HIV-1, 132 pol gene sequences were obtained and revealed eight HIV-1 subtypes. Circulating recombinant form (CRF)01_AE was the most frequent subtype (53.0%, 70/132) followed by CRF07_BC (26.5%, 35/132), B (13.6%, 18/132), unique recombinant forms (2.3%, 3/132), CRF55_01B (1.5%, 2/132), CRF103_01B (1.5%, 2/132), CRF65_cpx (0.8%, 1/132), and C (0.8%, 1/132). A total of 47 pol gene sequences were used to generate 10 molecular transmission networks. The overall prevalence of PDR was 7.6% and that of PDR to non-nucleotide reverse transcriptase inhibitors was 6.1%. Of three transmission networks for PDR, two were closely associated with Beijing and Tianjin, while another was restricted to sequences determined in this study.ConclusionsThese results demonstrate that during acute HIV-1 infection, PDR is transmitted in dynamic networks. This suggests that early detection, diagnosis, surveillance, and treatment are critical to effectively control HIV-1 spread.
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Project description:BackgroundGuangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong.ObjectiveTo investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong.MethodsHIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks.ResultsOf 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners.ConclusionDrug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links.
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Project description:Population-based sequencing of primary/recent HIV infections (PHIs) can provide a framework for understanding transmission dynamics of local epidemics. In Quebec, half of PHIs represent clustered transmission events. This study ascertained the cumulative implications of clustering on onward transmission of drug resistance.HIV-1 pol sequence datasets were available for all genotyped PHI (<6 months postseroconversion; n = 848 subtype B infections, 1997-2007). Phylogenetic analysis established clustered transmission events, based on maximum likelihood topologies having high bootstrap values (>98%) and short genetic distances. The distributions of resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors in unique and clustered transmissions were ascertained.Episodic clustering was observed in half of recent/early stage infections from 1997-2008. Overall, 29 and 28% of new infections segregated into small (<5 PHI/cluster, n = 242/848) and large transmission chains (> or =5 PHI/cluster, n = 239/848), averaging 2.8 +/- 0.1 and 10.3 +/- 1.0 PHI/cluster, respectively. The transmission of nucleoside analogue mutations and 215 resistant variants (T215C/D/I/F/N/S/Y) declined with clustering (7.9 vs. 3.4 vs. 1.2 and 5.8 vs. 1.7 vs. 1.1% for unique, small, and large clustered transmissions, respectively). In contrast, clustering was associated with the increased transmission of viruses harbouring resistance to nonnucleoside reverse transcriptase inhibitors (6.6 vs. 6.0 vs. 15.5%, respectively).Clustering in early/PHI stage infection differentially affects transmission of drug resistance to different drug classes. Public health, prevention and diagnostic strategies, targeting PHI, afford a unique opportunity to curb the spread of transmitted drug resistance.
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