ABSTRACT
OBJECTIVE: This study aims to investigate the prevalence and types of drug resistance mutations among patients failing first-line antiretroviral therapy (ART). METHODS: Plasma samples from 112 patients with human immunodeficiency virus-1 (HIV-1) were collected for virus RNA extract and gene amplification. The mutations related to drug resistance were detected and the incidence was statistically analyzed, and the drug resistance rate against common drugs was also evaluated. RESULTS: 103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. The incidence of drug resistance mutations was significantly different among patients with different ages, routes of infection, duration of treatment, initial ART regimens and viral load. The drug resistance rate to the common drugs was assessed, including Efavirenz (EFV, 71.84%), Nevirapine (NVP, 74.76%), Lamivudine (3TC, 66.02%), Zidovudine (AZT, 4.85%), Stavudine (D4T, 16.51%), and Tenofovir (TDF, 21.36%). CONCLUSION: The drug resistance mutations to NRTIs and NNRTIs are complex and highly prevalent, which was the leading cause of first-line ART failure. This study provides significant theoretical support for developing the second-line and third-line therapeutic schemes.
Subject(s)
Antiretroviral Therapy, Highly Active , Antiviral Agents/pharmacology , Benzoxazines/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Mutation , Nevirapine/pharmacology , Adult , Alkynes , Cyclopropanes , Female , Humans , Incidence , Lamivudine/pharmacology , Male , Middle Aged , Stavudine/pharmacology , Tenofovir/pharmacology , Treatment Failure , Viral Load , Zidovudine/pharmacologyABSTRACT
Interleukin-27 (IL-27) gene polymorphisms are linked to infectious disease susceptibility and IL-27 plasma level is associated with HIV infection. Therefore, we aimed to investigate the association between IL-27 polymorphisms and susceptibility to HIV infection and disease progression. A total of 300 patients with HIV infection (48 long-term nonprogressors and 252 typical progressors) and 300 healthy controls were genotyped for three IL-27 polymorphisms, rs17855750, rs181206, rs40837 which were performed by using multiple single nucleotide primer extension technique. Significant association was found between IL-27 rs40837 polymorphisms with susceptibility to HIV infection (AG vs AA: adjusted OR = 1.60, 95% CI, 1.11-2.30, P = 0.012; AG+GG vs AA: adjusted OR = 1.44, 95% CI, 1.02-2.03, P = 0.038) and disease progression (LTNP: AG vs AA: adjusted OR = 2.33, 95% CI, 1.13-4.80, P = 0.021; TP: AG vs AA: adjusted OR = 1.50, 95% CI, 1.04-2.24, P = 0.030). Serum IL-27 levels were significantly lower in cases compared to controls (P < 0.001). There were lower serum IL-27 levels in TPs than in LTNPs (P < 0.001). We further found that LTNPs with rs40837 AG or GG genotype had lower serum IL-27 levels than with AA genotype (P < 0.05). The CD4+ T counts in cases were significantly lower than controls (P < 0.001). In contrast, individuals with rs40837 AG genotype had lower CD4+ T counts than with AA genotype in cases (P < 0.05). In addition, CD4+ T counts in TPs were significantly lower than LTNPs (P < 0.001). IL-27 rs40837 polymorphism might influence the susceptibility to HIV infection and disease progression probably by regulating the level of serum IL-27 or the quantity of CD4+ T.