| Objective:Acquired immunodefieiency syndrome (AIDS)is a major infectious disease caused by the human immune eficiency virus (HIV). Subsequent to HIV infection,the immune function of the human body diminishes gradually, eventually resulting in death because of various occassional infections.Current treatments for AIDS include highly active antiretroviral therapy (HAART)can control the infection but do not eradicate the HIV virus.Their long-term treatment can cause side-effects and HIV drug-resistance mutations.Therefore, development of novel antiviral strategies is urgently needed. Collected here are 137 cases of HAART failure at the Yunnan Infectious Disease Hospital from January to December,2013.We conducted drug-resistance analyses of viral load and CD4+lymphocytes to explore the clinical efficacy of second-line antiviral therapy in Yunnan, China and provide theoretical support for HIV-I treatment options and optimization and develoment of novel antiviral strategies.Methods:With reference to international standards as well as second-line inclusion criteria for AIDS patients specified in 2012 edition of National Free Antiretroviral Drug Therapy Manual. From January to December 2013,137 cases of HAART failure were collected at the Infectious Disease Hospital of Yunnan Province, according to second-line priorities, and epidemiological and clinical data analyses were conducted, including demographic information, ART treatment and compliance data; laboratory tests included CD4 lymphocyte count, viral load determination; samples of VL greater than or equal to 1000 copies/ml were analyzed, and genotypic resistance testing analysis was conducted as well. All statistical tests were made with SPSS 17.0 software, and related factors before and after second-line treatment were analyzed with Logistic regression method.Results:Study of 137 cases of HAART failure, average age 39.8+10, with the main route of infection from heterosexual contact accounting for 51.09% 70/137. Prior to replacement of second-line antiviral drugs, the mean of CD4 cells was 224.47+84.07cells/mm3, VL (log) value was 3.92+0.594. The longest time for patients who underwent first-line treatment was 98 months, and the shortest 14 months. Total drug resistance rate is 75.19%(103/137) including NRTIs and NNRTIs resistance, resistance ratio respectively 40.98 (56/137) and 57.66% (79/137); NRTIs resistant mutant sites for the M184V, accounted for 37.22% (51/103), then the K65R (21.16%), d67n (25.54%). NNRTIs appear with the highest frequency, loci followed by K103N (35.3%), Y181C (27.01%), G190A/S (22.62%). All patients with replacement of second-line 3TC+TDF ten LPV/R received 6 months of treatment, with CD4 cell mean being 296.73+82.48; VL (log) mean 3.43+0.582. After treatment, total resistance decreased for 38.21%(47/123); NRTIs resistance rate went down 14.63%(18/123), but NNRTLs resistance loci M184V still stayed at about 9.75%(12/123). NNRTIs resistance rate dropped to 24.39%(30/123). Although NRTIs drugs as a second-line skeleton drugs are still in use, no increase of resistance loci was witnessed. It is worth noting that protease inhibitors have not yet found the main resistance loci. After 6 months of treatment, follow-up of 123 cases of AIDS patients in the second-line drug,64 of them failed viral suppression (VL> 400 copies/ml). For single factor Logistic regression analysis, see Table 9, CD4< 200 cells/mm3/patients (95%CI0.7-35.5, P= 0.01) and compliance with treatment outcome was statistically significant.Conclusion:1. This study found that the major route of infection was heterosexual contact, accounting for 51.09%(70/137). Prior to replacement of second-line antiviral drugs, the mean of CD4 cells was 224.47+84.07cells/mm3, VL (log) value was 3.92+0.594. Results show virological, immunological, and clinical failure.2.Found that AIDS patients on first-line regimens are liable to produce drug resistance and found that the total drug resistance rate is 75.19% 103/137; NRTIs resistance mutation M184V, accounted for 37.22% (51/103), followed by K65R accounting for 21.16% (29/137); d67n accounted for 25.54% (35/137), and the resistance loci of highest frequency for NNRTIs drugs are K103N 35.03%(48/137), Y181C 27.01% (37/137), G190A/S 22.62%(31/137).3. Found that after switch to second-line therapy, CD4 mean was 296.73+82.48; VL(log) mean 3.43+0.582, showing virological, immunological and clinical treatment effectivenss and success in immune functional reconstruction. Loci of main resistance for protease inhibitors have not yet appeared. Found that LPV/R resistance mutations may lead to a second-line treatment failure, and that LPV/R resistance mutation detection helps to choose and optimize treatment.From a public health perspective, it is critical to improve efforts to monitor the emergence of such mutations, to initiate and innovate ART and to monitor drug-naive individuals to check the spread of resistant variants. |
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