HIV Drug Resistance Surveillance Among Patients Receiving Antiretroviral Therapy

Objective:we conducted two prospective cohort study to learn the drug resistance among Chinese patients one year after initiating3TC-based first-line antiretroviral treatment and the prevalence of drug resistance after switching the second-line treatment.Methods:Two prospective cohort study1. The four sentinel surveys were conducted in urban areas of China, including Jiangsu province, Guizhou province, Hunan province and Chongqing Municipality, respectively. The survey was a prospective cohort study with follow-up at12months. Criteria for enrolling in the study were:previously antiretroviral naive,18years or older, agreeing to initiate ART in the NFATP, and willing to provide informed consent.2. Surveys were performed at sentinel sites in Queshan county, Weishi county and Xincai county, the three counties, where ART began earlier. The survey was a prospective cohort study with follow-up at6and12months after switching the second-line therapy. Criteria for enrolling in the study were:18years or older, receiving the first-line therapy at least12month, switching to the second-line therapy, and willing to provide informed consent.The two study subjects were recruited through sequential sampling at each clinic by receiving ART or switching the second-line therapy respectively, to participate in an one-year prospective cohort study. Laboratory test and epidemiological data were collected at the baseline and follow-up. Data were collected using an interviewer-administered questionnaire. Questionnaires included demographic data, ART treatment and self-reported adherence data., etc. All subjects provided blood specimens for testing CD4count, HFV viral load, and HIV drug resistance mutations (for samples with HIV-1RNA≥1000copies/ml). All tests of significance were two-sided, with p-value<0.05indicating that an association was statistically significant. Multivariable logistic regression was performed to examine the independent variables which was associated with HIV RNA<1000copies/ml at12months in the first-line or the second-line therapy.RESULTS:1. The first-line survey included513subjects, the mean age were38.8years (SD,±11.2years);9.2%were farmers;48.2%were infected through heterosexual intercourse; and the most common HIV viral subtype was CRF01_AE. All the initial ART regimen were including3TC, and the major therapy was AZT+3TC+NVP (59.1%). Of the448(87.3%) patients retained at12month, CD4cell count was313cells/mm3, which increased from the median192cells/mm3at baseline (P<0.0001). Among patients receiving ART for nearly one year,394(87.9%) patients had plasma HFV RNA<1000copies/ml. Among the54samples with viral load≥1000copies/ml,40were successfully genotyped. Of the11with detectable HIVDR mutations, the proportion of drug resistance to NNRTIs, NRTIs and PIs were27.5%(11/40),22.5%(9/40),0%(0), respectively. These three factors remained in the multivariable logistic regression model. Injecting drug use [adjusted odds ratio (aOR)=0.40,95%CI:0.19,0.84; P=0.0154], CD4count at baseline≥350cells/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 negatively associated with virological success.2. The second-line survey included303eligible subjects, the mean age were48.0years (SD,±8.6years);93.7%were infected through blood donation; and all the HIV viral subtype was B’. The early therapy was DDI+AZT/D4T+NVP (57.7%); before switching the regimen, the median time of receiving initial therapy was89month. As second-line treatment3TC+TDF+LPV/r were switched for all patients, and the median time of receiving second-line therapy was10month. According to the baseline viral load and drug resistance, patients were divided three groups:group A was drug resistance group and included60patients, Before switching, after switching6month, after switching12month, the rate of VL <1000copies/ml was100%,48.1%,41.8%(P<0.001), respectively. Group B was VL≥1000copies/ml without drug resistance and included30patients. Before switching, after switching6month, after switching12month, the rate of VL<1000copies/ml was100%,51.8%,48.1%(P<0.001), respectively. Group C was viral suppression (VL<1000copies/ml) and included213patients. Before switching, after switching6month, after switching12month, the rate of VL<1000copies/ml was0%,4.8%,6.5%, respectively. The reasons for switching regimen in group C were immunological failure53(4.9%), self-demanding switching38(17.8%), toxicity22(10.3%), HCV antibody positive30(14.1%), and the remaining for unknown reasons (32.9%). Among patients with viral suppression failure, the prevalence of resistance to NNRTIs, NRTIs, and PIs at baseline was65.5%,53.3%and1.1%, respectively and declined to26.8%,18.3%,0%, respectively after switching therapy. However receiving second-line therapy nearly for one year, of the NNRTI resistance mutations K103NS, Y181CY remained around10%, not disappearing; NRTIs drugs as second-line drugs were still using as basement, and the relate drug resistance was not increased. Meanwhile PIs resistance mutations were not detected. In multivariate analysis, the variables with viral suppression was:initial treatment with DDI, aOR=3.4(95%CI,1.1-11.0, P=0.04); missed doses in the past month, aOR=4.6(95%CI,1.6-13.4, P=0.005); not on time taking drug in the past month due to go out, aOR=3.6(95%CI,1.2-11.1, P=0.02).Conclusions:This HFVDR surveillance study in four sentinel sites across China demonstrates good virological and immunological outcomes at12months among these who initiated based3TC first-line ART treatment. However, patients infected through drug injection, who missed doses, are at increased risk for poor virological response. Patients with drug resistance show good outcomes after switching regimen, followed by patients with viral suppression failure. Adherence remains as an important factor affecting the therapeutic effect of the second-line therapy, so how to improve adherence is still the most important issue on ART treatment. Despite the prevalence of resistance to NRTI is high after long-term first-line treatment, but after switching the second-line regimen NRTI-based, it does not cause accumulation of resistance mutations or add new sites; Stopping NNRTI for one year, it still resistance to this class drugs. After switching the second-line drugs, the resistance to protease inhibitors is low within12months.