Prevalence of WHO Transmitted Drug Resistance Mutations by Deep Sequencing in Antiretroviral-Naïve Subjects in Hunan Province, China

Abstract

BackgroundThere are few data on the prevalence of WHO transmitted drug resistance mutations (TDRs) that could affect treatment responses to first line antiretroviral therapy (ART) in Hunan Province, China.ObjectiveDetermine the prevalence of WHO NRTI/NNRTI/PI TDRs in ART-naïve subjects in Hunan Province by deep sequencing.MethodsART-naïve subjects diagnosed in Hunan between 2010–2011 were evaluated by deep sequencing for low-frequency HIV variants possessing WHO TDRs to 1% levels. Mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility.ResultsDeep sequencing was performed on samples from 90 ART-naïve subjects; 83.3% were AE subtype. All subjects had advanced disease (average CD4 count 134 cells/mm3). Overall 25.6%(23/90) of subjects had HIV with major WHO NRTI/NNRTI TDRs by deep sequencing at a variant frequency level ≥1%; 16.7%(15/90) had NRTI TDR and 12.2%(11/90) had a major NNRTI TDR. The majority of NRTI/NNRTI mutations were identified at variant levels <5%. Mutations were analyzed by HIVdb.stanford.edu and 7.8% of subjects had variants with high-level nevirapine resistance; 4.4% had high-level NRTI resistance. Deep sequencing identified 24(27.6%) subjects with variants possessing either a PI TDR or hivdb.stanford.edu PI mutation (algorithm value≥15). 17(19.5%) had PI TDRs at levels >1%.ConclusionsART-naïve subjects from Hunan Province China infected predominantly with subtype AE frequently possessed HIV variants with WHO NRTI/NNRTI TDRs by deep sequencing that would affect the first line ART used in the region. Specific mutations conferring nevirapine high-level resistance were identified in 7.8% of subjects. The majority of TDRs detected were at variant levels <5% likely due to subjects having advanced chronic disease at the time of testing. PI TDRs were identified frequently, but were found in isolation and at low variant frequency. As PI/r use is infrequent in Hunan, the existence of PI mutations likely represent AE subtype natural polymorphism at low variant level frequency.

Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China

“…Early antiviral treatment can control virus replication as early as possible, and reduce the possibility of drug resistance [13,18]. The result showed that CRF01 AE is still the most dominance subtype in Hunan province (64.14%), followed by subtype BC,B and C, the finding corresponding to the last years of the Hunan Province molecular epidemiology survey (2009-2015) results [10][11][12]19].. The prevalence of HIV-1 subtype B was significantly higher in Zhangjiajie City compared with other areas in Hunan province.…”

“…The Chinese national free ARV treatment policy guidelines recommend that patients on ART should have an HIV viral load test at least once a year [10][11][12]. If the viral load is > 1000 copies/ml, a HIV drug resistance genotypic test (Sanger Sequencing based) should be performed.…”

“…Lopinavir/ritonavir (LPV/r), produce outside China, is the second-line drug. A recent Hunan Province molecular epidemiology survey showed that 4 HIV-1 subtypes in Hunan province reported were CRF_01AE, CRF07_BC, B and C. CRF_01AE was the dominant subtype strain (more than 70%) [10][11][12].…”

Increase of RT-Related Transmitted Drug Resistance in Non-CRF01_AE Among HIV Type 1–Infected Men Who Have Sex With Men in the 7 Cities of China

“…In recent years, more and more HIV-infected MSM have received the free antiretroviral treatment. 29 Another recent study has reported that RT-related TDRs were detected among MSM in Kunming. 30 Several drugs have low genetic bottleneck, and one point mutation can make HIV resistant to NNRTIs.…”

“…22,28,29 The increasing trend of TDR in some regions of China deserves the concern from public health departments and medical workers. 22,28,29 The increasing trend of TDR in some regions of China deserves the concern from public health departments and medical workers.…”