ABSTRACT
Objective: To investigate the distribution characteristics of the HIV genetic subtypes and the status quo of transmitted drug resistance among HIV/AIDS patients in Sichuan with no previous history of receiving antiretroviral therapy (ART). Methods: Adult HIV/AIDS patients who were hospitalized in Sichuan and who had no previous history of exposure to ART drugs exposure were enrolled. In-house sequencing of the HIV gene was done and phylogenetic tree was constructed to analyze the HIV genetic subtypes. The Stanford HIV drug resistance database was used to make online comparison of the drug resistance mutation sites and to determine the presence or absence of drug resistance, and the type and level of drug resistance. Results: A total of 120 patients were enrolled for the study, and 120 blood samples were collected. The genetic subtypes of 87.5% (105/120) of the samples were successfully amplified. The distribution characteristics of HIV genotype were as follows, CRF01_AE accounted for 46.67% (49/105), CRF07_BC accounted for 39.05% (41/105), and the others genetic subtypes, 14.28% (15/105). There were no significant differences between the different genetic subtypes in sex, age, ethnicity, HIV transmission route, drug resistance, baseline HIV RNA and baseline CD4 ( P>0.05). Drug-resistant mutation sites were detected in 25 samples, accounting for 20.83% (25/120) of all samples, with 16.67% (20/120) being potential drug resistance and 4.17% (5/120) being transmitted drug resistance. For the 24 samples found to be resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs), the mutation frequency of V179D/E was the highest. One patient showed resistance to protease inhibitors (PI) and the mutation site was M46I. No nucleoside reverse transcriptase inhibitor (NRTI) or integrase inhibitors (INTI) resistance were found. Conclusions: The main genetic subtypes of HIV/AIDS patients in Sichuan with no previous history of receiving ART were CRF01_AE and CRF07_BC. The incidence of transmitted drug resistance was low. The drug resistance detected in the study was predominantly resistance to NNRTIs. Baseline HIV drug resistance testing is of great significance for formulating effective ART regimens.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , HIV-1 , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/epidemiology , Adult , China/epidemiology , Drug Resistance, Viral/genetics , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/genetics , Humans , Integrase Inhibitors/pharmacology , Integrase Inhibitors/therapeutic use , Mutation , Phylogeny , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , RNA/pharmacology , RNA/therapeutic use , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic useABSTRACT
BACKGROUND: The regimen containing tenofovir disoproxil fumarate (TDF)+lamivudine or emtricitabine + efavirenz remains the recommended first-line antiretroviral therapy (ART) by the WHO. Limited studies, however, have been conducted on the incidence of renal impairment among Chinese patients with long-term exposure to TDF-containing ART regimens. METHODS: We retrospectively analyzed 269 eligible patients who had no comorbidities and received TDF-containing ART from July 2014 to April 2015. TDF-related renal impairment was defined as a decrease of eGFR by >25% from baseline or eGFR <90 ml/min/1.73 m2. Decreased renal function was defined as a decrease of eGFR by > 10 mL/min/1.73 m2 from baseline. RESULTS: 97.0% of study patients were male (median age 29, eGFR 124.0 ml/min/1.73 m2). After 168-week of ART, renal impairment occurred in 7 patients (2.7%). The incidence of decreased renal function was significantly higher at Week 168 compared with that observed at Week 12 (24.8% vs 3.7%, p < 0.001). In generalized estimating equation analysis, patients receiving ART for 144-week (aOR4.1, 95%CI 2.0-8.4) and 168-week (aOR8.4, 95%CI 4.2-16.4) were more likely to develop decreased renal function compared with those receiving ART for 12-week, so were the patients with a weight <58 kg (aOR2.3, 95%CI 1.2-4.3) and 58-66 kg (aOR2.0, 95%CI 1.0-3.8) compared to those with a weight ≥67 kg. At 168-week, 41.0% of 100 patients examined had elevated urine ß2-microglobulin levels, which were negatively correlated with eGFR (r = -0.22, p = 0.02). CONCLUSIONS: TDF-related renal impairment remained rare in HIV-positive Chinese patients with a median age of 29 years who had no comorbidities. A lower weight and duration of ART were associated with decreased renal function.
