| Background and ObjectivesThe introduction of highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in patients infected with HIV/AIDS, however, the emergence of multi-drug-resistant HIV variants has become one of the central reasons of virologic failure. Free antiretroviral therapy (ART) was introduced in China since 2003 and has been spread on a large-scale throughout the country. Due to the limited drug options available in China, it becomes more and more important to monitor HIV drug resistance in patients undergoing ART, ensuring the optimal curative effect of treatment. Previouly studies on primary drug-resistance in China showed discrepancy and no prospective cohort study was performed. The main goal of this study was to evaluate the prevalence of primary HIV-1 drug-resistance among treatment-naive patients and the development of drug-resistance in patients undergoing ART through prospective cohort study.Materials and MethodsA total of 237 treatment-naive patients from 20 regions were enrolled for the evaluation of primary HIV drug-resistance, CD4 cell counts, vrial load and home-brew genotypic drug resistance testing were done. In the subsequent multi-center study, 190 drug-naive patients were enrolled in 13 trial centers across China from February 7 to September 6, 2005. In this open-label study, subjects were randomly assigned to one of three regimens: zidovudine plus didanosine, stavudine plus lamivudine, zidovudine plus lamivudine, and each regimen plus nevirapine additionally. Subjects were received tests for genotyping drug resistance, plasma HIV RNA levels and CD4 cell count at the time point of before initiating antiretroviral therapy and 4, 12, 24, 36 and 52 weeks follow-up.ResultsThe cross-sectional survey of 237 treatment-naive patients from 20 regions including Henan, Yunnan and Shanghai etc. showed that most of them were infected before 2003 and 9 subtypes were found in the HIV-1 strains derived from the patients. Three patients had mutations associated resistance to drugs, one with high-level resistance to NRTIs, one with low-level resistance to PIs and the other one with high-level resistance to NNRTIs. The prevalence of primary drug resistance was only 1.3% (3/237).In the cohort of 190 patients undergoing treatment, 28 samples have viral load more than 1000 copies/ml after 12 weeks treatment, in which 17 samples(8.9%, 17/190) acquired drug-resistance mutations (ADM), with a regimen of AZT+DDI+NVP in 16 patients and D4T+3TC+NVP in the other one patient. Mutations associated with resistance to NNRTIs emerged in patients treated for less than 24 weeks, major including K103N, Y181C and G190A with a frequency of 35.3% (6/17),41.2%(7/17) and 29.4%( 5/17), respectively. NRTIs related mutations emerged in patients treated for more than 24 weeks, in which the most common mutation was T215Y(23.5%, 4/17) . After 52 weeks treatment, 13 of 15 (86.7%) samples with viral load more than 1000 copies/ml had drug-resistance mutations. The significant risk factor of ADM was poor adherence (<95%) and the regimen of AZT+DDI+NVP. The rates of patients with undectable viral load (<50 copies/ml) in the three regimen D4T+3TC+NVP, AZT+3TC +NVP and AZT+DDI+NVP were 68.8%, 70.4% and 40.3%, respectively. Poor adherence and the emergence of ADM were proved to be the main obstacle of effective antiretroviral therapy.ConclusionsThis study was the first prospective drug-resistance research in China, with the most subjects, the widest covering area, the most subtypes and the longest range of infection time. The rate of primary drug-resistance was at a very low level. Acquired drug -resistance mutations was the main obstacle of treatment failure in patients with insufficient viral suppression and poor adherence was the main risk of ADM. Patients with the regimen of AZT+DDI+NVP trended to have low rate of viral suppression and high rate of drug resistance and this regimen was not recommended to be first-line treatment regimen.
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