I-21 Prevalence of drug resistant HIV-1 in rural areas of Hubei province in the People's Republic of China
ABSTRACT To determine the prevalence of drug-resistant HIV-1 and the efficacy of first-line highly active antiretroviral therapy (HAART) regimens consisted of generic nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor among 339 study subjects in rural areas of Hubei province, China.
Two cross-sectional studies were conducted to investigate 150 HAART-naive (99 received subsequent therapy) between 2003 and 2005 and 288 HAART-experienced patients mainly between 2005 and 2006. Patients' CD4+ T-cell count and viral load were determined. HIV-1 pol gene fragments were amplified from patients' plasma by reverse transcriptase-polymerase chain reaction, subsequently sequenced and analyzed.
About 83.5% of the patients were from rural villages. They were dominantly infected with subtype B' HIV-1 (96.7%) through paid blood donation (64.6%) and related blood transfusion (28.3%). We found that there was a steady increase of CD4 count over time among treated patients without detectable viral load (186/288, 64.6%). There was, however, an increasing prevalence of nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant mutations among patients with detected viremia (102/288, 35.4%) after treatment for 3-6 (24.3%), 9-12 (57.1%), and 20-24 (63.3%) months, respectively. The increasing rates were associated with significant CD4 count drop and viral load increase. Some patients also developed multidrug-resistant mutants.
: We report the first HIV-1 drug resistance study after 2 years on HAART among Chinese patients living in rural villages. Our data suggest that a significant portion of patients are failing first-line regimens with a trend of AIDS progression. It is therefore necessary to maximize the drug adherence and to make affordable second-line HAART regimens available immediately. Our results have implications for implementing HAART in underresourced developing country settings.
Full-textDOI: · Available from: Ke Zhuang, Sep 24, 2014
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ABSTRACT: Objective To understand drug resistance prevalence among treatment-failure and treatment-naive HIV-positive individuals in China. Methods We searched five electronic databases (Wanfang, CNKI, CQVIP, SinoMed, and Pubmed) for studies of HIV drug resistance. Random-effects models were carried out to estimate the prevalence of drug resistance among treatment-failure and treatment-naive individuals, respectively. Results The estimated nationwide rates of HIV drug resistance to any-class drugs among treatment-failure and treatment-naive individuals were 57% (95% CI: 49%-65%) and 3.23% (95% CI: 2.47%-4.07%), respectively. Among the drug classes, the prevalence of resistance to PIs was low (1.45%; 95% CI: 0.73%-2.33%) in treatment-failure individuals, although high rates of resistance to NNRTIs (54%; 95% CI: 45%-63%) and NRTIs (40%; 95% CI: 32%-49%) were found. Resistance to any-class drugs, NNRTIs and NRTIs manifested regional differences, but resistance to PIs did not. Positive correlations were observed between resistance to NNRTIs and NRTIs among treatment-failure and treatment-naive individuals, respectively. Conclusion The prevalence of HIV drug resistance to NNRTIs and NRTIs among treatment-failure individuals was high. In contrast, the prevalence of drug resistance among treatment-naive individuals was low. The epidemics of drug resistance matched current treatment strategies and interventions in China. Surveillance for HIV drug resistance is necessary to assess the sustainability and durability of current treatment regimens.Biomedical and Environmental Sciences 11/2014; 27(11):858-71. DOI:10.3967/bes2014.123 · 1.26 Impact Factor
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ABSTRACT: Previously, we reported the conversion of the 12-mer linear and cell-impermeable peptide CAI to a cell-penetrating peptide NYAD-1 by using an i,i + 4 hydrocarbon stapling technique and confirmed its binding to the C-terminal domain (CTD) of the HIV-1 capsid (CA) protein with an improved affinity (Kd ~ 1 muM) compared to CAI (Kd ~ 15 muM). NYAD-1 disrupts the formation of both immature- and mature-like virus particles in in vitro and cell-based assembly assays. In addition, it displays potent anti-HIV-1 activity in cell culture against a range of laboratory-adapted and primary HIV-1 isolates. In this report, we expanded the study to i,i + 7 hydrocarbon-stapled peptides to delineate their mechanism of action and antiviral activity. We identified three potent inhibitors, NYAD-36, -66 and -67, which showed strong binding to CA in NMR and isothermal titration calorimetry (ITC) studies and disrupted the formation of mature-like particles. They showed typical alpha-helical structures and penetrated cells; however, the cell penetration was not as efficient as observed with the i,i + 4 peptides. Unlike NYAD-1, the i,i + 7 peptides did not have any effect on virus release; however, they impaired Gag precursor processing. HIV-1 particles produced in the presence of these peptides displayed impaired infectivity. Consistent with an effect on virus entry, selection for viral resistance led to the emergence of two mutations in the gp120 subunit of the viral envelope (Env) glycoprotein, V120Q and A327P, located in the conserved region 1 (C1) and the base of the V3 loop, respectively. The i,i + 7 stapled peptides derived from CAI unexpectedly target both CA and the V3 loop of gp120. This dual-targeted activity is dependent on their ability to penetrate cells as well as their net charge. This mechanistic revelation will be useful in further modifying these peptides as potent anti-HIV-1 agents.Retrovirology 11/2013; 10(1):136. DOI:10.1186/1742-4690-10-136 · 4.77 Impact Factor
HIV Therapy 09/2009; 3(5):485-499. DOI:10.2217/hiv.09.28