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Efficacy Of 3TC+D4T+NVP Regimen Anti-HIV-1 Treatment And Drug Resistance Mutations

Posted on:2010-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y BiFull Text:PDF
GTID:2144360275966429Subject:Epidemiology and Health Statistics
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ObjectivesTo evaluated the effect of 3TC+D4T+NVP treatment regimen, and explore the occurrence and the prevalence of drug-resistant strains after received the HIV-1 antiretroviral treatment, and to explore the type and frequency of drug-resistance mutations in protease and reverse transcriptase gene .Methods72 antiretroviral treatment na?ve HIV-infected persons from Nanning City or the LiuZhou City (control group), and 114 HIV-infected persons who were antiretroviral treatment na?ve but about to be treated with antiretroviral drugs (treatment group) from the same areas were recruited in the present study. All 186 subjects were surveyed with questionnaires to get demographic information and epidemiological data, such as when to acquired infection, time of confirmation, and so on. Peripheral venous blood from all subjects were collected, and were subjected to plasma virus loads detetion and CD4~+T lymphocyte count analysis. After 6 months of treatment with antiiretroviral drugs, a survey were conducted in treament groupt to find out the medication compliance, and then peripheral venous blood were also collected from all subjects of the two groups. Plasma viral loads and CD4~+T lymphocyte count were detected, in addition, viral RNA were extracted from plasma samples, and HIV-1 protease and reverse transcriptase gene were amplified by RT-PCR. The PCR products were sequenced and 100 sequences of HIV-1 protease gene and reverse transcriptase gene fragment were obtained. The sequences were submitted to Stanford HIV Drug Resistance Database ( http://hivdb.stanford.edu) to get information about mutations related to HIV-1 drug resistance.Results1. There were statistically significant with regard to viral loads pre-treatment and after 6 months of treatment (P <0.05) in the treatment group, meaning that plasma viral load decreased after antiretroviral treatment. There were no significant difference in of two detections in control group(P>0.05). The viral loads after 6 months were not significantly different between treatment group and control group (P>0.05), viral load was lower in treatment group than in control group (P <0.05).2. CD4~+T lymphocyte counts in the treatment group were significantly higher after 6 month of antiretroviral treatment than pre-treatment (P<0.05). CD4~+T lymphocyte counts were significantly lower in treatment group pretreated than in untreatment group at corresponding time (P<0.05), but were not significantly different after 6 month (P>0.05). Repeated ANOVA analysis showed a different trend between treatment and control group (P﹤0.01) , CD4~+T lymphocyte counts obviously increased with time in treatment group, but didn't in untreatment group.3. A total sequences of 62 pol gene were obtained from 72 samples of control group. One sample was found to harboured M46L, a PIs major mutations, and the frequency of M46L was 1.61% (1/62). Two samples harboured secondary mutations, L10LV and L10I, their frequency was 3.23% (2/62). There were six NRTIs associated mutations occur in four samples, the incidence rate was 6.45% (4/62). The frequency of both T69N and T215Y was 6.45% (4/62) , and was 3.23% (2/62) for V75L, and 1.61% (1/62) for L74I, K219KR, and D67E, respectively. NNRTIs related mutations were not find in control group. One sample had mutations confered at least low-level resistance to one or more pIs, the resistance rate was 1.61 (1/62). Four samples were found to be low or higher resistant to at least one or more NRTIs, the resistance rate was 6.25% for NRTIs.4. A total of 34 pol gene sequence were otained from 114 samples from treatment group. Only one PIs major resistance-related mutation, M46L, was found in one sample, and its frequency was 2.94% (1/34). Only one secondary mutations, L10V, was found in one sample too, also giving a frequency of 2.94% (1/34). There were 9 mutations confered resistance to NRTIs, and M184V was the most common mutation with a frequency of 11.76%(4/34). There were 12 NNRTIs-related mutations, and G190AG (8.82%), K238T (5.88%), and P225H (5.88%) were more common than other mutations. The rates of resistance to PIs and NRTIs/NNRTIs were 2.94% and 11.76%, respectively.5. The resistance rate was 11.76% in treatment group and 6.25% in non-treatment group, but there were no significantly difference between the two groups (P>0.05).Conclusions1. Patients treated with the 3TC+D4T+NVP regimen for 6 months can have a high rate of viral suppression and CD4~+T lymphocyte recovery.2. The resistance rate of naive HIV-1 infected patients is low, indicating that there is a low prevalence of drug resistance in Guangxi.3. The frequencies of PIs,NRTIs and NNRTIs related mutations are relatively low in untreated group, and the frequencies of PIs related mutation is also low in treatment group, however, more kinds and higher frequencies of NRTIs and NNRTIs related mutations are found in this group.4. Resistance rate in patients treated with 3TC+D4T+NVP for 6 months is as similar as that in untreated patients.
Keywords/Search Tags:AIDS, HIV-1, genotypic resistance, genetic mutation
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