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HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013.

ABSTRACT: BACKGROUND:The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C'-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country. METHODS:A cross-sectional survey was conducted among young antiretroviral therapy (ART)-naïve individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011-2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST. RESULT:Four of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C'-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate. CONCLUSION:TDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C'-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.

SUBMITTER: Arimide DA

PROVIDER: S-EPMC6179264 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013.

Arimide Dawit Assefa DA Abebe Almaz A Kebede Yenew Y Adugna Fekadu F Tilahun Tesfaye T Kassa Desta D Assefa Yibeltal Y Balcha Taye Tolera TT Björkman Per P Medstrand Patrik P

PloS one 20181010 10

<h4>Background</h4>The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C'-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country.<h4>Methods</h4>A cross-sectional survey was conducted among young antiretroviral ...[more]

PMID: 30304061

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Project description:ObjectivesTo assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up.MethodsPopulation sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001.Results47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events.ConclusionsTransmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.

Project description:BackgroundTransmitted drug resistance (TDR) reduces the efficacy of initial antiretroviral treatment and has become a public health concern. Little information is available regarding the genetic diversity of HIV-1 and the prevalence of TDR among treatment-naïve patients in a northwestern province of China since the implementation of national free antiretroviral therapy (ART).MethodsBlood samples from 372 HIV-1 treatment-naive patients were collected between 2003 and 2013 in Shaanxi province. Viral RNA was extracted for nested PCR, and phylogenetic reconstruction and recombination analyses were performed to characterize patterns of the HIV-1 subtypes. Genotypic drug resistance testing was performed using an in-house assay to determine trends in the prevalence of HIV-1 transmitted drug resistance.ResultsMultiple genotypes were identified among the patients in Shaanxi, including B (25.0%), C (0.3%), G (0.3%), and CRF01_AE (39.2%), CRF07_BC (32.7%), CRF08_BC (0.8%), CRF55_01B (1.1%), and URFs (0.6%). The subtypes were associated with the transmission routes (χ2 = 77.113, p < 0.01). In this study, a low baseline CD4+ T cell count and a high viral load were found among CRF01_AE-infected patients compared with patients who were infected with non-CRF01_AE (p<0.01) through sexual transmission; however, the CRF01_AE subtype was not associated with a low baseline CD4+ T cell count or a high viral load in Chinese patients infected through blood transmission (p = 0.249). The overall TDR rate in this population was 4.4% between 2003 and 2013. A univariate logistic regression model revealed that a low CD4 T cell count (≤ 100 cells/µL) was associated with the development of drug-resistant strains.ConclusionOur work revealed diverse HIV-1 subtype distributions in Shaanxi province. We identified a low and stable TDR time trend among ART-naive patients. These findings enhance our understanding of HIV-1 genetic diversity and provide some guidelines for the improvement and implementation of a comprehensive public health strategy of HIV-1 TDR prevention.

Dataset Information

HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013.

Publications

HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013.

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