Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Zheng DP[original query] |
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High prevalence of pre-treatment HIV drug resistance in Papua New Guinea: findings from the first nationally representative pre-treatment HIV drug resistance study.
Gare J , Toto B , Pokeya P , Le LV , Dala N , Lote N , John B , Yamba A , Soli K , DeVos J , Paulin H , Wagar N , Zheng DP , Nishijima T , Boas P , Kelly-Hanku A , Gurung A . BMC Infect Dis 2022 22 (1) 266 BACKGROUND: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. METHODS: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. RESULTS: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8-24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6-23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6-17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1-56.4%). CONCLUSIONS: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG. |
Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings
Zhang G , DeVos J , Medina-Moreno S , Wagar N , Diallo K , Beard RS , Zheng DP , Mwachari C , Riwa C , Jullu B , Wangari NE , Kibona MS , Ng'Ang'A LW , Raizes E , Yang C . PLoS One 2018 13 (9) e0203296 INTRODUCTION: Surveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naive populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART. METHODS: EDTA-venous blood was collected to prepare DBS from adult and pediatric ART patients receiving treatment during the previous 12-36 months. DBS were stored at ambient temperature for two weeks and then at -80 degrees C until shipment at ambient temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta. Viral load (VL) was determined using NucliSENS EasyQ(R) HIV-1 v2.0 kits; HIVDR genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits. RESULTS: DBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these specimens had VL >/=1,000 copies/mL in Kenya and Tanzania, respectively. The overall genotyping rate of those DBS with VL >/=1,000 copies/mL was 93.0% (95% CI: 89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times for the HIVDR surveys from the time of collecting DBS to completing laboratory testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys, respectively. CONCLUSIONS: The study demonstrates a favorable outcome of using DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm that DBS collected and stored at ambient temperature for two weeks, and shipped with routine courier services are a reliable sample type for large-scale surveillance of acquired HIVDR. |
Pretreatment HIV drug resistance among adults initiating ART in Namibia
Taffa N , Roscoe C , Sawadogo S , De Klerk M , Baughman AL , Wolkon A , Mutenda N , DeVos J , Zheng DP , Wagar N , Prybylski D , Yang C , Hamunime N , Agolory S , Raizes E . J Antimicrob Chemother 2018 73 (11) 3137-3142 Background: Continued use of standardized, first-line ART containing NNRTIs and NRTIs may contribute to ongoing emergence of HIV drug resistance (HIVDR) in Namibia. Methods: A nationally representative cross-sectional survey was conducted during 2015-16 to estimate the prevalence of significant pretreatment HIV drug resistance (PDR) and viral load (VL) suppression rates 6-12 months after initiating standardized first-line ART. Consenting adult patients (>/=18 years) initiating ART were interviewed about prior antiretroviral drug (ARV) exposure and underwent resistance testing using dried blood spot samples. PDR was defined as mutations causing low-, intermediate- and high-level resistance to ARVs according to the 2014 WHO Surveillance of HIV Drug Resistance in Adults Initiating ART. The prevalence of PDR was described by patient characteristics, ARV exposure and VL results. Results were weighted to be nationally representative. Results: Successful genotyping was performed for 381 specimens; 144 (36.6%) specimens demonstrated HIVDR, of which 54 (12.7%) demonstrated PDR. Resistance to NNRTIs was most prevalent (11.9%). PDR was higher in patients with previous ARV exposure compared with no exposure (30.5% versus 9.6%) (prevalence ratio = 3.17; P < 0.01). Conclusions: This survey demonstrated overall PDR at >10% among adults initiating ART in Namibia. Patients with prior ARV exposure had higher rates of PDR. Introducing a non-NNRTI-based regimen for first-line ART should be considered to maximize benefit of ART and minimize the emergence of HIVDR. |
Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy.
Zhou Z , Tang K , Zhang G , Wadonda-Kabondo N , Moyo K , Rowe LA , DeVos JR , Wagar N , Zheng DP , Guo H , Nkengasong J , Frace M , Sammons S , Yang C . Afr J Lab Med 2018 7 (1) 708 Background: Minority drug resistance mutations (DRMs) that are often missed by Sanger sequencing are clinically significant, as they can cause virologic failure in individuals treated with antiretroviral therapy (ART) drugs. Objective: This study aimed to estimate the prevalence of minor DRMs among patients enrolled in a Malawi HIV drug resistance monitoring survey at baseline and at one year after initiation of ART. Methods: Forty-one plasma specimens collected from HIV-1 subtype C-positive patients and seven clonal control samples were analysed using ultra-deep sequencing technology. Results: Deep sequencing identified all 72 DRMs detected by Sanger sequencing at the level of >/=20% and 79 additional minority DRMs at the level of < 20% from the 41 Malawian clinical specimens. Overall, DRMs were detected in 85% of pre-ART and 90.5% of virologic failure patients by deep sequencing. Among pre-ART patients, deep sequencing identified a statistically significant higher prevalence of DRMs to nucleoside reverse transcriptase inhibitors (NRTIs) compared with Sanger sequencing. The difference was mainly due to the high prevalence of minority K65R and M184I mutations. Most virologic failure patients harboured DRMs against both NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). These minority DRMs contributed to the increased or enhanced virologic failures in these patients. Conclusion: The results revealed the presence of minority DRMs to NRTIs and NNRTIs in specimens collected at baseline and virologic failure time points. These minority DRMs not only increased resistance levels to NRTIs and NNRTIs for the prescribed ART, but also expanded resistance to additional major first-line ART drugs. This study suggested that drug resistance testing that uses more sensitive technologies, is needed in this setting. |
Massive iatrogenic outbreak of human immunodeficiency virus type 1 in rural Cambodia, 2014-2015
Rouet F , Nouhin J , Zheng DP , Roche B , Black A , Prak S , Leoz M , Gaudy-Graffin C , Ferradini L , Mom C , Mam S , Gautier C , Lesage G , Ken S , Phon K , Kerleguer A , Yang C , Killam W , Fujita M , Mean C , Fontenille D , Barin F , Plantier JC , Bedford T , Ramos A , Saphonn V . Clin Infect Dis 2017 66 (11) 1733-1741 Background: In 2014-2015, 242 individuals aged 2-89 were newly HIV-1 diagnosed in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C and B viruses (HCV, HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV, and HBcIgM Ab for HBV. We performed evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed health care practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were co-infected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P=0.04). Fifty-nine (38.6%) of 153 tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed three main clades, one containing 34 subtypes 1b with tMRCA in 2012, and two with 51 subtypes 6e and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically-diverse HCV propagation. |
Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria.
Yang C , Diallo K , Zheng DP , Rottinghaus EK , Bassey OO . AIDS Res Hum Retroviruses 2015 31 (5) 564-75 Studying the genetic diversity and natural polymorphisms of HIV-1 would benefit our understanding of HIV drug resistance (HIVDR) development and predict treatment outcomes. In this study, we have characterized the HIV-1 genetic diversity and natural polymorphisms at the 5' region of pol gene encompassing the protease (PR) and reverse transcriptase (RT) from 271 plasma specimens collected in 2008 from HIV-1-infected patients who were eligible for initiating antiretroviral therapy in Abuja (Nigeria). The analysis indicated that the predominant subtype was subtype G (31.0%), followed by CRF02-AG (19.2 %), CRF43-02G (18.5%), A/CRF36-cpx (11.4%) and the remaining (19.9%) were other subtypes and circulating (CRF) and unique (URF) recombinant forms. Recombinant viruses (68.6%) were the major viral strains in the region. Eighty-four subtype G sequences were further classified into two major and two minor clusters; sequences in the two major clusters were closely related to the HIV-1 strains in two of the three major subtype G clusters detected worldwide. Those in the two minor clusters appear to be new subtype G strains circulating only in Abuja. The pre-treatment DR prevalence was < 3%, however, numerous natural polymorphisms were present. Eleven polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T, R57K, L63P, and V82I) were detected in the PR that were subtype or CRF specific while only 3 mutations (D123N, I135T and I135V) were identified in the RT. Overall, this study indicates an evolving HIV-1 epidemic in Abuja with recombinant viruses becoming the dominant strains and emergence of new subtype G strains; pre-treatment HIVDR was low and natural polymorphism occurrence in PR region was subtype or CRF dependent. |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance.
Zheng DP , Rodrigues M , Bile E , Nguyen DB , Diallo K , Devos JR , Nkengasong JN , Yang C . PLoS One 2013 8 (10) e77649 Detection of recent HIV infections is a prerequisite for reliable estimations of transmitted HIV drug resistance (t-HIVDR) and incidence. However, accurately identifying recent HIV infection is challenging due partially to the limitations of current serological tests. Ambiguous nucleotides are newly emerged mutations in quasispecies, and accumulate by time of viral infection. We utilized ambiguous mutations to establish a measurement for detecting recent HIV infection and monitoring early HIVDR development. Ambiguous nucleotides were extracted from HIV-1 pol-gene sequences in the datasets of recent (HIVDR threshold surveys [HIVDR-TS] in 7 countries; n=416) and established infections (1 HIVDR monitoring survey at baseline; n=271). An ambiguous mutation index of 2.04x10(-3) nts/site was detected in HIV-1 recent infections which is equivalent to the HIV-1 substitution rate (2x10(-3) nts/site/year) reported before. However, significantly higher index (14.41x10(-3) nts/site) was revealed with established infections. Using this substitution rate, 75.2% subjects in HIVDR-TS with the exception of the Vietnam dataset and 3.3% those in HIVDR-baseline were classified as recent infection within one year. We also calculated mutation scores at amino acid level at HIVDR sites based on ambiguous or fitted mutations. The overall mutation scores caused by ambiguous mutations increased (0.54x10(-2)3.48x10(-2)/DR-site) whereas those caused by fitted mutations remained stable (7.50-7.89x10(-2)/DR-site) in both recent and established infections, indicating that t-HIVDR exists in drug-naive populations regardless of infection status in which new HIVDR continues to emerge. Our findings suggest that characterization of ambiguous mutations in HIV may serve as an additional tool to differentiate recent from established infections and to monitor HIVDR emergence. |
Molecular Epidemiology of Genogroup II-Genotype 4 Noroviruses in the United States between 1994 and 2006
Zheng DP , Widdowson MA , Glass RI , Vinje J . J Clin Microbiol 2009 48 (1) 168-77 Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV-outbreaks reported to CDC from 1994-2006. Of these, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were GII.4 strains. The proportion of GII.4-outbreaks increased from 5% in 1994 to 85% in 2006 but distinct annual differences were noted including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of complete VP1 gene of GII.4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct sub-clusters which had 1.3-3.2% amino acid variation between strains in different sub-clusters. We propose that GII.4 sub-clusters be defined as having > 5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains. |
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