Objective To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment. Methods A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance. Results A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm3, which increased from 192 cells/mm3 at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use (AOR = 0.40, 95% CI: 0.19,0.84; P = 0.0154), CD4 count at baseline ≥350 cells/mm3 (AOR = 0.32, 95% CI: 0.14,0.72; P = 0.0056), and missed doses in the past month (AOR = 0.30, 95% CI: 0.15,0.60; P = 0.0006) were significantly negatively associated with HIV RNA <1000 copies/ml. Conclusions Our study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response.
References
[1]
Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, et al. (1999) Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 341: 1865–1873. doi: 10.1056/nejm199912163412501
[2]
MacArthur RD, Novak RM, Peng G, Chen L, Xiang Y, et al. (2006) A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial. Lancet 368: 2125–2135. doi: 10.1016/s0140-6736(06)69861-9
[3]
Gabillard D, Lewden C, Ndoye I, Moh R, Segeral O, et al. (2013) Mortality, AIDS-morbidity, and loss to follow-up by current CD4 cell count among HIV-1-infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration. J Acquir Immune Defic Syndr 62: 555–561. doi: 10.1097/qai.0b013e3182821821
[4]
Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, et al. (2007) Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 21: 685–692. doi: 10.1097/qad.0b013e32802ef30c
[5]
Borrell C, Rodriguez-Sanz M, Pasarin MI, Brugal MT, Garcia-de-Olalla P, et al. (2006) AIDS mortality before and after the introduction of highly active antiretroviral therapy: does it vary with socioeconomic group in a country with a National Health System? Eur J Public Health 16: 601–608. doi: 10.1093/eurpub/ckl062
[6]
Joint United Nations Programme on HIV/AIDS. Together we will end AIDS. (Update 2012). Available: http://www.unaids.org/en/media/unaids/co?ntentassets/documents/epidemiology/2012/?20120718_ togetherwewillendaids_en.pdf. Accessed 2012 Jul 19.
[7]
Chinese Center for Disease Control and Prevention: Analysis of HIV/STD epidemic in 2012. Beijing, China.
[8]
Zhang F, Dou Z, Ma Y, Zhang Y, Zhao Y, et al. (2011) Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study. Lancet Infect Dis 11: 516–524. doi: 10.1016/s1473-3099(11)70097-4
[9]
Zhang F, Dou Z, Ma Y, Zhao Y, Liu Z, et al.. (2009) Five-year outcomes of the China National Free Antiretroviral Treatment Program. Ann Intern Med 151: 241–251, W-252.
[10]
Zhang F, Dou Z, Yu L, Xu J, Jiao JH, et al. (2008) The effect of highly active antiretroviral therapy on mortality among HIV-infected former plasma donors in China. Clin Infect Dis 47: 825–833. doi: 10.1086/590945
[11]
Liao L, Xing H, Su B, Wang Z, Ruan Y, et al. (2013) Impact of HIV drug resistance on virologic and immunologic failure and mortality in a cohort of patients on antiretroviral therapy in China. AIDS 27: 1815–1824. doi: 10.1097/qad.0b013e3283611931
[12]
Xing H, Ruan Y, Li J, Shang H, Zhong P, et al. (2013) HIV drug resistance and its impact on antiretroviral therapy in Chinese HIV-infected patients. PLoS One 8: e54917. doi: 10.1371/journal.pone.0054917
[13]
Xing H, Wang X, Liao L, Ma Y, Su B, et al. (2013) Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment. PLoS One 8: e62408. doi: 10.1371/journal.pone.0062408
[14]
Wang X, He C, Xing H, Liao L, Xu X, et al. (2012) Short communication: emerging transmitted HIV type 1 drug resistance mutations among patients prior to start of first-line antiretroviral therapy in middle and low prevalence sites in China. AIDS Res Hum Retroviruses 28: 1637–1639. doi: 10.1089/aid.2012.0164
[15]
Liao L, Xing H, Dong Y, Qin G, Ma Y, et al. (2012) Surveys of transmitted HIV drug resistance in 7 geographic Regions in China, 2008–2009. Clin Infect Dis 54 Suppl 4S320–323. doi: 10.1093/cid/cir1016
[16]
Protocol for population-based monitoring of HIVDR emerging during treatment and related program factors at sentinel ART clinics: 2012 update. Available: http://apps.who.int/iris/bitstream/10665?/75205/1/WHO_HIV_2012.15_eng.pdf. Accessed 2013 Jun 16.
[17]
Wang X, Yang L, Li H, Zuo L, Liang S, et al. (2011) Factors associated with HIV virologic failure among patients on HAART for one year at three sentinel surveillance sites in China. Curr HIV Res 9: 103–111. doi: 10.2174/157016211795569122
[18]
Ruan Y, Xing H, Wang X, Tang H, Wang Z, et al. (2010) Virologic outcomes of first-line HAART and associated factors among Chinese patients with HIV in three sentinel antiretroviral treatment sites. Trop Med Int Health 15: 1357–1363. doi: 10.1111/j.1365-3156.2010.02621.x
[19]
Manual of the National Free Antiretroviral Treatment, third edition. Available: http://www.chinaaids.cn/jszn/201301/t201?30111_75763.htm.pdf. Accessed 2013 Jun 12.
[20]
Shafer RW, Rhee SY, Pillay D, Miller V, Sandstrom P, et al. (2007) HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS 21: 215–223. doi: 10.1097/qad.0b013e328011e691
[21]
Liu TF, Shafer RW (2006) Web resources for HIV type 1 genotypic-resistance test interpretation. Clin Infect Dis 42: 1608–1618. doi: 10.1086/503914
[22]
Zhong P, Pan Q, Ning Z, Xue Y, Gong J, et al. (2007) Genetic diversity and drug resistance of human immunodeficiency virus type 1 (HIV-1) strains circulating in Shanghai. AIDS Res Hum Retroviruses 23: 847–856. doi: 10.1089/aid.2006.0196
[23]
McMahon JH, Elliott JH, Bertagnolio S, Kubiak R, Jordan MR (2013) Viral suppression after 12 months of antiretroviral therapy in low- and middle-income countries: a systematic review. Bull World Health Organ 91: 377–385E. doi: 10.2471/blt.12.112946
[24]
Wadonda-Kabondo N, Bennett D, van Oosterhout JJ, Moyo K, Hosseinipour M, et al. (2012) Prevalence of HIV drug resistance before and 1 year after treatment initiation in 4 sites in the Malawi antiretroviral treatment program. Clin Infect Dis 54 Suppl 4S362–368. doi: 10.1093/cid/cir987
[25]
Laurent C, Diakhate N, Gueye NF, Toure MA, Sow PS, et al. (2002) The Senegalese government’s highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS 16: 1363–1370. doi: 10.1097/00002030-200207050-00008
[26]
Koenig SP, Leandre F, Farmer PE (2004) Scaling-up HIV treatment programmes in resource-limited settings: the rural Haiti experience. AIDS 18 Suppl 3S21–25. doi: 10.1097/00002030-200406003-00005
[27]
Smith D, Berrey MM, Robertson M, Mehrotra D, Markowitz M, et al. (2000) Virological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infection. J Infect Dis 182: 950–954. doi: 10.1086/315753
[28]
Boileau C, Nguyen VK, Sylla M, Machouf N, Chamberland A, et al. (2008) Low prevalence of detectable HIV plasma viremia in patients treated with antiretroviral therapy in Burkina Faso and Mali. J Acquir Immune Defic Syndr 48: 476–484. doi: 10.1097/qai.0b013e31817dc416
[29]
Fielding KL, Charalambous S, Stenson AL, Pemba LF, Martin DJ, et al. (2008) Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: a cohort study. BMC Infect Dis 8: 93. doi: 10.1186/1471-2334-8-93
[30]
Ma Y, Zhao D, Yu L, Bulterys M, Robinson ML, et al. (2010) Predictors of virologic failure in HIV-1-infected adults receiving first-line antiretroviral therapy in 8 provinces in China. Clin Infect Dis 50: 264–271. doi: 10.1086/649215
[31]
Rodriguez-Arenas MA, Jarrin I, del Amo J, Iribarren JA, Moreno S, et al. (2006) Delay in the initiation of HAART, poorer virological response, and higher mortality among HIV-infected injecting drug users in Spain. AIDS Res Hum Retroviruses 22: 715–723. doi: 10.1089/aid.2006.22.715
[32]
Ruan Y, Liang S, Zhu J, Li X, Pan SW, et al. (2013) Evaluation of harm reduction programs on seroincidence of HIV, hepatitis B and C, and syphilis among intravenous drug users in southwest China. Sex Transm Dis 40: 323–328. doi: 10.1097/olq.0b013e31827fd4d4
[33]
World Health Organization (WHO). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. June 2013. Available: http://www.who.int/hiv/pub/guidelines/ar?v2013/en/index.html.pdf. Accessed 2013 Jul 11.
[34]
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, et al. (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365: 493–505. doi: 10.1056/nejmoa1105243
[35]
Uy J, Armon C, Buchacz K, Wood K, Brooks JT, et al. (2009) Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 51: 450–453. doi: 10.1097/qai.0b013e3181acb630
[36]
Resistance UKCGoHD (2010) Group UCS (2010) Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy. Clin Infect Dis 50: 1275–1285. doi: 10.1086/651684
[37]
Zhu H, Napravnik S, Eron J, Cole S, Ma Y, et al. (2012) Attrition among human immunodeficiency virus (HIV)- infected patients initiating antiretroviral therapy in China, 2003–2010. PLoS One 7: e39414. doi: 10.1371/journal.pone.0039414