Background The emergence and transmission of HIV-1 drug resistance (HIVDR) has raised concerns after rapid global antiretroviral therapy (ART) scale-up. There are limited data on the epidemiology of primary HIVDR in resource-limited settings in Asia. We aimed to determine the prevalence and compare the distribution of HIVDR in a cohort of ART-na？ve Asian patients with recent and chronic HIV-1 infection. Methods Multicenter prospective study was conducted in ART-na？ve patients between 2007 and 2010. Resistance-associated mutations (RAMs) were assessed using the World Health Organization 2009 list for surveillance of primary HIVDR. Results A total of 458 patients with recent and 1,340 patients with chronic HIV-1 infection were included in the analysis. The overall prevalence of primary HIVDR was 4.6%. Recently infected patients had a higher prevalence of primary HIVDR (6.1% vs. 4.0%, p = 0.065) and frequencies of RAMs to protease inhibitors (PIs; 3.9% vs. 1.0%, p<0.001). Among those with recent infection, the most common RAMs to nucleoside reverse transcriptase inhibitors (NRTIs) were M184I/V and T215D/E/F/I/S/Y (1.1%), to non-NRTIs was Y181C (1.3%), and to PIs was M46I (1.5%). Of patients with chronic infection, T215D/E/F/I/S/Y (0.8%; NRTI), Y181C (0.5%; non-NRTI), and M46I (0.4%; PI) were the most common RAMs. K70R (p = 0.016) and M46I (p = 0.026) were found more frequently among recently infected patients. In multivariate logistic regression analysis in patients with chronic infection, heterosexual contact as a risk factor for HIV-1 infection was less likely to be associated with primary HIVDR compared to other risk categories (odds ratio 0.34, 95% confidence interval 0.20–0.59, p<0.001). Conclusions The prevalence of primary HIVDR was higher among patients with recent than chronic HIV-1 infection in our cohort, but of borderline statistical significance. Chronically infected patients with non-heterosexual risks for HIV were more likely to have primary HIVDR.
References
[1]
Johansson KA, Robberstad B, Norheim OF (2010) Further benefits by early start of HIV treatment in low income countries: survival estimates of early versus deferred antiretroviral therapy. AIDS Res Ther 7: 3.
[2]
Jongwutiwes U, Sungkanuparph S, Kiertiburanakul S (2008) Comparison of clinical features and survival between cryptococcosis in human immunodeficiency virus (HIV)-positive and HIV-negative patients. Jpn J Infect Dis 61: 111–115.
[3]
Joint United Nations Programme on HIV/AIDS and World Health Organization: Global report (2010) UNAIDS report on the global AIDS epidemic 2010. WHO Library Cataloguing-in-Publication. Available: http://www.unaids.org/globalreport/docum？ents/20101123_GlobalReport_full_en.pdf. Assessed 25 September 2012.
[4]
Geretti AM (2007) Epidemiology of antiretroviral drug resistance in drug naive persons. Curr Opin Infect Dis 20: 22–32.
[5]
Hamers RL, Wallis CL, Kityo C (2011) HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis 11: 750–759.
[6]
Division of HIV/AIDS Epidemiology and Surveillance, National HIV and Retrovirology Laboratories, Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada, Health Canada: HIV-1 strain and primary drug resistance in Canada (2006) Available: http://www.phacaspc.gc.ca/publicat/hiv1-？vih1/pdf/hiv-1-strain-01-e.pdf. Assessed 25 September 2012.
[7]
World Health Organization: Monitoring the emergence of antiretroviral resistance. Report of a WHO consultation organized in collaboration with Istituto di Sanità and the International AIDS Society, Rome, Italy (2000) Available: http://apps.who.int/medicinedocs/documen？ts/s16347e/s16347e.pdf. Assessed 25 September 2012.
[8]
Apisarnthanarak A, Jirayasethpong T, Sa-nguansilp C, Thongprapai H, Kittihanukul C, et al. (2008) Antiretroviral drug resistance among antiretroviral-naive persons with recent HIV infection in Thailand. HIV Med 9: 322–325.
[9]
Apisarnthanarak A, Mundy LM (2008) Antiretroviral drug resistance among antiretroviral-naive individuals with HIV infection of unknown duration in Thailand. Clin Infect Dis 46: 1630–1631.
[10]
Gagliani LH, Alkmim Maia WT, Sa-Filho D (2011) The association between primary antiretroviral resistance and HAART virologic failure in a developing set. AIDS Res Hum Retroviruses 27: 251–256.
[11]
Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, et al. (2002) Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med 347: 385–394.
[12]
Charpentier C, Bellecave P, Cisse M, Mamadou S, Diakite M, et al. (2011) High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger. Antivir Ther 16: 429–433.
[13]
Grant RM, Hecht FM, Warmerdam M, Liu L, Liegler T, et al. (2002) Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA 288: 181–188.
[14]
Vergne L, Diagbouga S, Kouanfack C, Aghokeng A, Butel C, et al. (2006) HIV-1 drug-resistance mutations among newly diagnosed patients before scaling-up programmes in Burkina Faso and Cameroon. Antivir Ther 11: 575–579.
[15]
Hamers RL, Oyomopito R, Kityo C, Phanuphak P, Siwale M, et al. (2012) The PharmAccess African (PASER-M) and the TREAT Asia (TASER-M) Monitoring Studies to Evaluate Resistance–HIV drug resistance in sub-Saharan Africa and the Asia-Pacific. Int J Epidemiol 41: 43–54.
[16]
Bennett DE, Bertagnolio S, Sutherland D, Gilks CF (2008) The World Health Organization's global strategy for prevention and assessment of HIV drug resistance. Antivir Ther 13: 1–13.
[17]
Land S, Cunningham P, Zhou J, Frost K, Katzenstein D, et al. (2009) TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories. J Virol Methods 159: 185–193.
[18]
Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H, et al. (2009) Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 4: e4724.
[19]
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infec ted adults and adolescents. DHHS. March 27, 2012 (2012) Available at: http://www.aidsinfo.nih.gov/contentfiles？/lvguidelines/adultandadolescentgl.pdf. Assessed 25 September 2012.
[20]
Kuritzkes DR (2004) Preventing and managing antiretroviral drug resistance. AIDS Patient Care STDS 18: 259–273.
[21]
Nguyen HT, Duc NB, Shrivastava R, Tran TH, Nguyen TA, et al. (2008) HIV drug resistance threshold survey using specimens from voluntary counselling and testing sites in Hanoi, Vietnam. Antivir Ther 13: 115–121.
[22]
Sirivichayakul S, Phanuphak P, Pankam T, O-Charoen R, Sutherland D, et al. (2008) HIV drug resistance transmission threshold survey in Bangkok, Thailand. Antivir Ther 13: 109–113.
[23]
Sungkanuparph S, Oyomopito R, Sirivichayakul S, Sirisanthana T, Li PC, et al. (2011) HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study. Clin Infect Dis 52: 1053–1057.
[24]
Zhao B, Han X, Dai D, Liu J, Ding H, et al. (2011) 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 27: 1047–1053.
[25]
Kiertiburanakul S, Sungkanuparph S (2009) Emerging of HIV drug resistance: epidemiology, diagnosis, treatment and prevention. Curr HIV Res 7: 273–278.
[26]
Sungkanuparph S, Kiertiburanakul S, Sukasem C, Chantratita W (2012) Discrepancies Between WHO 2009 and IASUSA 2009 Lists for Determining the Rate of Transmitted HIV-1 Drug Resistance: A Prospective Study. J Acquir Immune Defic Syndr 59: e3–5.
[27]
Lee CC, Sun YJ, Barkham T, Leo YS (2009) Primary drug resistance and transmission analysis of HIV-1 in acute and recent drug-naive seroconverters in Singapore. HIV Med 10: 370–377.
[28]
Sirivichayakul S, DeLong A, Wongkunya R, Mekprasan S, Sohn AH, et al.. Increasing HIV drug resistance among recently infected treatment-na？ve MSM in Thailand: results from three years annual surveillance. In program and abstract of the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention (Rome), July 17–20, 2011 (2011) [abstract MOPE053]
[29]
Haidara A, Chamberland A, Sylla M, Aboubacrine SA, Cissé M, et al. (2010) High level of primary drug resistance in Mali. HIV Med 11: 404–411.
[30]
Riva C, Violin M, Cozzi-Lepri A, Aboubacrine SA, Cissé M, et al. (2002) Transmitted virus with substitutions at position 215 and risk of virological failure in antiretroviral-naive patients starting highly active antiretroviral therapy. Antivir Ther 7: S103–104.
[31]
Violin M, Cozzi-Lepri A, Velleca R, Vincenti A, D'Elia S, et al. (2004) Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy. AIDS 18: 227–235.
[32]
Johnson VA, Brun-Vezinet F, Clotet B, Günthard HF, Kuritzkes DR, et al. (2010) Update of the drug resistance mutations in HIV-1: December 2010. Top HIV Med 18: 156–163.
[33]
Eiros JM, Labayru C, Hernández B, Ortega M, Bachiller P, et al. (2002) Prevalence of genotypic resistance in untreated HIV patients in Spain. Eur J Clin Microbiol Infect Dis 21: 310–313.
[34]
Ammaranond P, Cunningham P, Oelrichs R, Suzuki K, Harris C, et al. (2003) Rates of transmission of antiretroviral drug resistant strains of HIV-1. J Clin Virol 26: 153–161.
[35]
Larder BA, Kemp SD (1989) Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246: 1155–1158.
[36]
Picard V, Angelini E, Maillard A, Race E, Clavel F, et al. (2001) Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. J Infect Dis 184: 781–784.
[37]
Maphalala G, Okello V, Mndzebele S, Gwebu P, Mulima N, et al. (2008) Surveillance of transmitted HIV drug resistance in the Manzini-Mbabane corridor, Swaziland, in 2006. Antivir Ther 13 suppl 2: 95–100.
[38]
Inocencio LA, Pereira AA, Sucupira MC, Fernandez JC, Jorge CP, et al. (2009) Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals recently diagnosed with HIV. J Int AIDS Soc 12: 20.
[39]
Rhee SY, Liu T, Ravela J, Gonzales MJ, Shafer RW (2004) Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother 48: 3122–3126.
