摘要
Objective:To explore the relationship between drug resistance occurrence and the distribution pattern of polymorphic loci in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) treated with highly active anti-retroviral therapy (HAART).Methods:HAART-failed HIV/AIDS patients who successfully amplified the gene sequences of the pol region between June 2015 and December 2021 from 16 prefecture-level administrative regions in Yunnan Province were included.The resistant sequences were classified using the human immunodeficiency virus (HIV) basic local alignment search tool (BLAST) and validated through MEGA 6.0, and the obtained sequences were submitted to the Stanford University HIV Drug Resistance Database to identify drug resistance loci. The distribution of polymorphic loci was analyzed across patients exhibiting varying degrees of drug resistance, different treatment regimens and distinct HIV-1 subtypes.Changes of the frequencies of polymorphic loci in patients with different degrees of drug resistance were analyzed using trend chi-square test. Statistical comparisons and further paired comparisons were performed using chi-square test.Results:Gene sequences were amplified from 1 453 patients, and the resistance testing results showed 954 sensitive, 224 potentially or low resistant, 189 moderately resistant, and 86 highly resistant patients. The frequencies of mutations I15V, L19I, D60E in the HIV-1 protease region (PR region) and E36A, T39D, S48T mutations in the HIV-1 reverse transcriptase region (RT region) showed a decreasing trend as the degree of HIV-1 resistance escalated ( χ2trend=19.86, 9.16, 13.66, 37.64, 18.44 and 40.86, respectively, all P<0.01). Conversely, the mutations V77I in the PR region and K122E in the RT region showed an ascending trend ( χ2trend=12.19 and 10.03, respectively, both P<0.01). Distinct treatment groups, namely zidovudine (AZT)+ lamivudine (3TC)+ lopinavir/ritonavir (LPV/r), AZT+ 3TC+ efavirenz (EFV), AZT+ 3TC+ nevirapine (NVP), and tenofovir (TDF)+ 3TC+ EFV, were examined. Statistically significant differences in the frequencies of mutations E35D, M36I, and D60E in the PR region, as well as S48T, K122E, and R211K in the RT region, were observed among these treatment groups ( χ2=22.46, 9.32, 14.46, 26.85, 18.92 and 24.26, respectively, all P<0.05). In paired comparisons, AZT+ 3TC+ LPV/r group displayed higher frequencies of E35D, M36I, and D60E mutations, the AZT+ 3TC+ EFV group showed a higher frequency of S48T mutation, the AZT+ 3TC+ NVP group showed a higher frequency of K122E mutation, and the TDF+ 3TC+ EFV group exhibited a higher frequency of R211K mutation, all with statistically significant differences (all P<0.008). The differences in the frequencies of T12S, I15V, L19I, M36I, V77I, L89M in the PR region and E53D, I135V, S162C, R211K, K277R in the RT region among circulating recombinant form (CRF)08_BC, CRF07_BC and CRF01_AE subtype group were statistically significant ( χ2=693.60, 712.51, 798.11, 434.85, 386.91, 657.78, 932.58, 409.21, 344.39, 469.44 and 260.48, respectively, all P<0.001). In paired comparisons, the frequencies of T12S, I15V, L19I, E53D, I135V, S162C and R211K in CRF08_BC subtype, the frequencies of V77I and K277R in CRF07_BC subtype, and the frequencies of M36I and L89M in CRF01_AE subtype were higher than those in the other two groups, and the differences were all statistically significant (all P<0.017). Conclusions:The polymorphic loci resulting from HIV-1 HAART failure show different distribution patterns across various degrees of drug resistance, treatment regimens and HIV-1 subtypes.These loci demonstrate both specific and shared characteristics. It is necessary to enhance the surveillance of select polymorphic loci.
摘要
Objective To investigate the influence factors of mortality among human immunodeficiency virus (HIV)-infected children under highly active antiretroviral therapy (HAART).Methods Retrospective cohort study of 652 children initiated HAART from 2005 to 2014 was conducted,and enrolled patients were followed-up until December,2015.Survival data was analyzed using Kaplan-Meier method and Cox regression model was used to identify independent predictors of mortality among these children on HARRT.Chi-square test and Fisher's exact test were used for comparison between groups.Results Overall,26 of the children died over a follow-up period of 3 116.24 child-years,with a mortality rate of 0.83 per 100 child-years.Twelve (46％)of deaths occurred during the first six months after starting HAART.Cox regression analysis of variables showed that the World Health Organization (WHO) clinical stages Ⅲ/Ⅳ (hazard rate [HR] =10.717,95％confidence interal [95％ CI]:4.189-4.749,P =0.000),baseline hemoglobin ＜ 80 g/L (HR =14.768,95 ％ CI:5.721-38.125,P =0.000),tuberculosis co-infection (HR =4.794,95％ CI:2.105-10.918,P =0.000),baseline CD4+T lymphocyte ＜ 50 cells/μL (HR =4.219,95％ CI:1.524-11.680,P =0.006),weight-for-age z-score ＜-2 (HR =2.983,95 ％ CI:1.094-8.135,P =0.033) were independently associated with death,whereas the age ＜ 7 year-old at HAART initiation was protectire (HR =0.293,95％ CI:0.126-0.684,P =0.005).Conclusions The mortality of children receiving HAART is strongly associated with WHO stages Ⅲ/Ⅳ,hemoglobin ＜ 80 g/L,weight-for-age z-score ＜-2,tuberculosis co-infection and older age at treatment.