Liu J, Yue J, Wu S, et al. Polymorphisms and drug resistance analysis of HIV-1 CRF01_AE strains circulating in Fujian Province, China
ABSTRACT The database of genotypic drug resistance mutations in HIV-1 subtype B circulating in developed industrial countries has been well established; however, little is known regarding the prevalence of genotypic resistance patterns in patients harboring non-subtype-B HIV-1 variants in most Asian countries.
To characterize the polymorphisms and emergence of drug-resistance mutations, resistance to antiretroviral drugs in naïve and pretreated patients infected with HIV-1 CRF01_AE isolates in Fujian province, China.
HIV-1 pol amplicons from 52 pre- and 14 post-treatment samples were obtained by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. All of the 14 antiretroviral-treated patients were under a fixed regimen of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), and they had been on treatment for a mean of 6 months (SD, 4 months). The sequence data were analyzed using the Bioedit software, and the data regarding drug resistance mutations were obtained using the Stanford software ( http://hivdb.stanford.edu ).
In comparison with the consensus sequence of B strains, the most common protease polymorphisms in HIV-1 CRF01_AE strains prevailing in Fujian Province, China, were I13V (76.9%), E35D (76.9%), M36I (100%), R41K (98.1%), H69K (90.4%), and L89M (96.2%). Protease mutations between CRF01_AE strains and B' variants prevailing in China were observed. The proportion of substitutions L63P, A71T/V, V77I and I93L in subtype B' sequences was considerably higher than in CRF01_AE viruses, while the proportion of L10I, M36I and K20R/I substitutions in subtype B' sequences was relatively lower than in CRF01_AE strains. A high level of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) (28.6%, 4/14) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (35.7%, 5/14) was found in treatment-experienced patients. High-level resistance to nevirapine (NVP) and lamivudine (3TC) was found in the stavudine/lamivudine/nevirapine (d4T/3TC/NVP) treatment regimen. The overall drug resistance rate was 42.9% (6/14), the resistance rates to two and to all three drugs under treatment were 14.3% (2/14) and 7.1% (1/14), respectively.
This study is the first report on polymorphisms and emergence of drug-resistance mutations in HIV-1 subtype CRF01_AE prevailing in China. These findings provide useful information on global HIV genetic variability and non-B drug resistance.
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- "The problem of drug resistance is compounded by the worldwide dissemination of multiple different subtypes of HIV-1 and the fact that natural polymorphisms in both HIV-1 and HIV-2 can affect the emergence of drug resistance to currently approved drugs (Kantor and Katzenstein, 2003; Ntemgwa et al., 2007; Stranix et al., 2004). Furthermore, polymorphisms within the PR enzyme may not themselves be responsible for resistance but can contribute to the development of high-level resistance if other mutations are present (Bessong, 2008; Kantor and Katzenstein, 2003; Liu et al., 2007; Velazquez-Campoy et al., 2003; Vergne et al., 2000). It is therefore important to understand antiviral activity and drug resistance profiles in viruses of different subtypes. "
ABSTRACT: PL-100 is a novel HIV-1 protease inhibitor (PI) that maintains activity against viruses that are resistant to other PIs. To further characterize this compound, we used it to select for drug resistance in tissue culture, using two non-B HIV-1 subtypes, viz. subtype C and a CRF01_AE recombinant virus. PL-100 selected for both minor and major PI resistance mutations along either of two distinct pathways. One of these involved the V82A and L90M resistance mutations while the other involved a mutation at position T80I, with other mutations being observed at positions M46I/L, I54M, K55R, L76F, P81S and I85V. The resistance patterns in both subtype C and CRF01_AE were similar and an accumulation of at least three mutations in the flap and active sites were required in each case for high-level resistance to occur, demonstrating that PL-100 has a high genetic barrier against the development of drug resistance.Antiviral research 09/2010; 87(3):367-72. DOI:10.1016/j.antiviral.2010.06.001 · 3.94 Impact Factor
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ABSTRACT: We evaluated the prevalence and profile of antiretroviral treatment (ART)-associated resistance mutations among HIV-1 strains in northern Vietnam by genotypically analyzing strains isolated from ART-naive individuals in Hai Phong, a city in which HIV-1 is highly prevalent. Plasma samples were collected from injecting drug users (IDU, n = 760), female sex workers (FSW, n = 91), seafarers (n = 94), pregnant women (n = 200), and blood donors (n = 210), and screened for HIV-1 antibodies. Plasma viral RNA was extracted from HIV-1-positive samples, amplified by reverse transcriptase (RT)-PCR of protease and RT genes, and analyzed for genotypes and ART-associated resistance mutations. HIV-1 prevalence among IDU, FSW, seafarers, pregnant women, and blood donors was 35.9%, 23.1%, 0%, 0.5%, and 2.9%, respectively. Phylogenetic analyses revealed that the most prevalent HIV-1 subtype was CRF01_AE (98.3%), similar to strains prevalent in southern China. Four (1.4%) subtype B strains and one (0.3%) unique recombinant between subtypes B and C were also identified. We found protease inhibitor-associated major resistance mutations in one of the 294 cases analyzed (0.3%; mutation M46I). We found RT inhibitor-associated major resistance mutations in 7/273 cases (2.6%; one occurrence each of L74I, M184I, and K219E; three cases of K103N; and two cases of G190E). One CRF01_AE strain harboring a protease codon 35 insertion was first identified in Vietnam. Thus, monitoring of drug-resistant HIV-1 and establishment of a database are required for the proper selection of ART in Vietnam.AIDS research and human retroviruses 03/2009; 25(2):175-82. DOI:10.1089/aid.2008.0193 · 2.46 Impact Factor
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ABSTRACT: HIV-1 nonsubtype B variants account for the majority of HIV infections worldwide. Drug resistance in individuals who have never undergone antiretroviral therapy can lead to early failure and limited treatment options and, therefore, is an important concern. Evaluation of reported transmitted drug resistance (TDR) is challenging owing to varying definitions and study designs, and is further complicated by HIV-1 subtype diversity. In this article, we discuss the importance of various mutation lists for TDR definition, summarize TDR in nonsubtype B HIV-1 and highlight TDR reporting and interpreting challenges in the context of HIV-1 diversity. When examined carefully, TDR in HIV-1 non-B protease and reverse transcriptase is still relatively low in most regions. Whether it will increase with time and therapy access, as observed in subtype-B-predominant regions, remains to be determined.HIV Therapy 09/2009; 3(5):447-465. DOI:10.2217/hiv.09.30