Transmitted Antiretroviral Drug Resistance and Thumb Subdomain Polymorphisms Among Newly HIV Type 1 Diagnosed Patients Infected with CRF01_AE and CRF07

Abstract

The aim of this study was to elucidate the prevalence of transmitted drug-resistant (TDR) mutations and reverse transcriptase (RT) thumb subdomain polymorphisms in CRF01_AE and CRF07_BC virus among newly diagnosed, therapy-naive HIV-1 patients in Guangdong Province, China. One hundred and sixty-four samples were collected in the Guangzhou Eighth People's Hospital. The entire protease gene and 300 codons of the entry part of the reverse transcriptase were amplified and sequenced. Furthermore, genotypic drug resistance, polymorphisms, and their phylogeny were analyzed. According to eligibility criteria, seven samples were excluded, and 119 of 157 (75.8%) samples (84 CRF01_AE and 35 CRF07_BC) were amplified and sequenced successfully. The prevalence of TDR identified in the present study was 6.7% [8/119, 95% confidence interval (CI) 1.8–11.6%]. Three major resistance mutations, K103N, M184V, and Y188L, each of which caused more than one drug resistance, appeared in only two patients; the prevalence [1.7 % (2/119)] was relatively low. Until now, this is the first observation of the five newly identified accessory mutations, V35T, K43E, V60I, K122E, and E203D, and seven thumb subdomain polymorphisms, A272P, K277R, K281R, T286A, E291D, V292I, and I293V, in the RT gene in China. These findings provide useful information for guidance on the antiretroviral therapy (ART) policy in China where therapeutic options are still limited.

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References

Department of Public Health, Guangdong province. The report of HIV/AIDS prevention and control work in 2011. http://zwgk.gd.gov.cn/006940132/201112/t20111206_294678.html?. 2011 04 12(in Chinese).

Liao

, Xing

, Shang

et al. The prevalence of transmitted antiretroviral drug resistance in treatment-naive HIV-infected individuals in China. J Acquir Immune Defic Syndr, 2010; 53:10–14.

Laeyendecker

, Zhang

, Quinn

et al. Molecular epidemiology of HIV-1 subtypes in southern China. J Acquir Immune Defic Syndr, 2005; 38:356–362.

Deng

, Fu

, Bao

et al. Molecular epidemiological tracing of HIV-1 outbreaks in Hainan island of southern China. AIDS, 2009; 23:977–985.

, Li

et al. Prevalence and evolution of drug resistance HIV-1 variants in Henan, China. Cell Res, 2005; 15:843–849.

Zhao

, Han

, Dai

et al. New trends of primary drug resistance among HIV Type 1-infected men who have sex with men in Liaoning Province, China. AIDS Res Hum Retroviruses, 2011; 27:1–4.

Hattori

, Shiino

, Gatanaga

et al. Trends in transmitted drug-resistant HIV-1 and demographic characteristics of newly diagnosed patients: Nationwide surveillance from 2003 to 2008 in Japan. Antiviral Res, 2010; 88:72–79.

Nguyen

, Duc

, Shrivastava

et al. HIV drug resistance threshold survey using specimens from voluntary counselling and testing sites in Hanoi, Vietnam. Antivir Ther, 2008; 13:115–121.

Kim

, Chin

, Han

et al. Low prevalence of drug-resistant HIV-1 in patients newly diagnosed with early stage of HIV infection in Korea. Tohoku J Exp Med, 2008; 216:259–265.

10.

Choi

, Kim

, Park

, Lee

, Kim

. National survey for drug-resistant variants in newly diagnosed antiretroviral drug-naive patients with HIV/AIDS in South Korea: 1999–2005. J Acquir Immune Defic Syndr, 2008; 49:237–242.

11.

Bennett

, Myatt

, Bertagnolio

et al. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment. Antivir Ther, 2008; 13:25–36.

12.

Han

, Zhang

, Dai

et al. Genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV/AIDS patients living in Liaoning Province, China: Baseline prevalence and subtype-specific difference. AIDS Res Hum Retroviruses, 2007; 23:357–364.

13.

Goldsamt

, Clatts

, Parker

et al. Prevalence of sexually acquired antiretroviral drug resistance in a community sample of HIV-positive men who have sex with men in New York City. AIDS Patient Care STDS, 2011; 25:287–293.

14.

Yerly

, Junier

, Gayet-Ageron

et al. The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection. AIDS, 2009; 23:1415–1423.

15.

Parker

, Gordon

, Reilly

et al. Prevalence of drug-resistant and nonsubtype B HIV strains in antiretroviral-naive, HIV-infected individuals in New York State. AIDS Patient Care STDS, 2007; 21:644–652.

16.

Cane

, Green

, Fearnhill

, Dunn

. the UK collaborative group on HIV Drug Resistance. Identification of accessory mutations associated with high-level resistance in HIV-1 reverse transcriptase. AIDS, 2007; 21:447–455.

17.

Svicher

, Sing

, Santoro

et al. Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. J Virol, 2006; 80:7186–7198.

18.

Huigen

, van Ham

, de Graaf

, Kagan

, Boucher

, Nijhuis

. Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Retrovirology, 2008; 5:20–31.

19.

Garriga

, Pérez-Elías

, Delgado

et al. HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with virological failure to nucleoside drug combinations. J Antimicrob Chemother, 2009; 64:251–258.

20.

Betancor

, Puertas

, Nevot

et al. Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure. Antimicrob Agents Chemother, 2010; 54:4799–4811.

Transmitted Antiretroviral Drug Resistance and Thumb Subdomain Polymorphisms Among Newly HIV Type 1 Diagnosed Patients Infected with CRF01_AE and CRF07_BC Virus in Guangdong Province,China

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