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Zhang J.,Institute of AIDS HIV Control and Prevention | Zhang J.,Centers for Disease Control and Prevention | Kang D.,Institute of AIDS HIV Control and Prevention | Lin B.,Institute of AIDS HIV Control and Prevention | And 5 more authors.
AIDS Research and Human Retroviruses | Year: 2012

Shandong province has been providing antiretroviral therapy (ART) to eligible HIV/AIDS patients since 2003 using first-line regimens. We conducted a cross-sectional study to assess virological response and resistance development from ART patients. Between 2006 and 2008, blood was collected from 143 ART patients. Viral load (VL) was determined with a detection limit of 50 copies/ml; those with detectable VL were genotyped with dried plasma spots using a broadly sensitive genotyping assay. Resistance mutations were identified using the Stanford HIV drug resistance database. Of the 143 patients, 72% [95% confidence interval (CI): 65.9-78.2] suppressed their VL to <50 copies/ml. Genotyping analysis of the remaining 40 patients revealed that 21 (53%, CI: 37.0-68.0) harbored one or more mutations. The most common mutations were thymidine-analog mutations (22.5%) and M184V (10%) to nucleoside reverse transcriptase inhibitors (NRTIs), and V106I/A /M (17.5%), Y181C (15%), and H221Y (12.5%) to non-NRTIs (NNRTIs); 13 patients had mutations to both NRTIs and NNRTIs. Patients with VL >1000 copies/ml appear to harbor more mutations than those with VL between 50 and 1000 (62.1% vs. 27.3%, p>0.05). Resistance mutations were intensified among 10 patients for whom two sequential specimens were obtained and accumulation of resistance mutations predicted compromised treatment outcomes and future drug selections. This study provides a snapshot of the virological responses and resistance profiles for patients on first-line regimens, indicating that patient monitoring is a critical component in preventing the accumulation of resistance mutations among patients failing their regimens and thus maintaining the effectiveness of the first-line regimens. © Copyright 2012, Mary Ann Liebert, Inc.


Zhang J.,Institute of AIDS HIV Control and Prevention | Zhang J.,Centers for Disease Control and Prevention | Kang D.,Institute of AIDS HIV Control and Prevention | Fu J.,Institute of AIDS HIV Control and Prevention | And 5 more authors.
AIDS Research and Human Retroviruses | Year: 2010

A survey to measure transmitted HIV-1 drug resistance (DR) was conducted in 2006 following the World Health Organization threshold survey protocol. Dried blood spots (DBS) were prepared from 53 newly HIV-1-diagnosed patients. Protease and reverse transcriptase (RT) gene regions were sequenced using a broadly sensitive genotyping assay and analyses to identify DR mutations and determine phylogeny of the HIV-1 strains were conducted. Forty-six of the 47 successfully genotyped DBS had no transmitted DR mutations; one had an NNRTI mutation (K101E) in the RT region. Phylogenetic analyses revealed 21 (44.7%) were CRF01-AE, 9 (19.1%) B, 6 (12.8%) CRF07-BC, 3 (6.4%) each of CRF08-BC and C, and 2 (4.3%) B/C unique recombinant forms (URF). The remaining three were one each of A/B, A/C, and unclassifiable. Our analyses indicate that the prevalence of transmitted DR in this population is low and the HIV-1 epidemic in the area was characterized by multiple subtypes and recombinant forms. © 2010, Mary Ann Liebert, Inc.


Yang C.,Centers for Disease Control and Prevention | McNulty A.,Centers for Disease Control and Prevention | Diallo K.,Centers for Disease Control and Prevention | Zhang J.,Centers for Disease Control and Prevention | And 11 more authors.
Journal of Clinical Microbiology | Year: 2010

As antiretroviral therapy (ART) is scaled up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first-line ART. We have developed and applied a broadly sensitive dried-blood-spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS samples were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (n = 58), Tanzania (n = 60), and China (n =53). In addition, 30 DBS and 40 plasma specimens collected from ART patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed at the protease and RT regions, 149 (87.1%) could be genotyped, including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART patient samples analyzed, 100% (30/30) of the Chinese DBS and 90% (36/40) of the Cameroonian plasma specimens were genotyped, including 8 samples with a viral load of <400 copies/ml. The results of phylogenetic analyses indicated that the subtype, circulating recombinant form (CRF), and unique recombinant form (URF) distribution was as follows: 73 strains were subtype C (34%), 37 were subtype B (17.2%), 24 each were CRF01-AE or CRF02-AG (11.2% each), 22 were subtype A1 (10.2%), and 9 were unclassifiable (UC) (4.2%). The remaining samples were minor strains comprised of 6 that were CRF07-BC (2.8%), 5 that were CRF10-CD (2.3%), 3 each that were URF-A1C and CRF08-BC (1.4%), 2 each that were G, URF-BC, and URF-D/UC (0.9%), and 1 each that were subtype F1, subtype F2, and URF-A1D (0.5%). Our results indicate that this broadly sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

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