Prevalence of Drug-Resistant HIV-1 in Rural Areas of Hubei Province in the People's Republic of China

Tsinghua University, Peping, Beijing, China
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 02/2009; 50(1):1-8. DOI: 10.1097/QAI.0b013e31818ffcdc
Source: PubMed


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.

Download full-text


Available from: Ke Zhuang, Sep 24, 2014
  • Source
    • "Highly active antiretroviral therapy (HAART), which has been successfully used in reducing AIDS-related deaths in the past 16 years, is usually composed of three antiviral drugs including reverse transcriptase inhibitors (RTI) and protease inhibitors (PI) targeting the post-entry phase (Hammer et al., 1996; Lu et al., 2012). Although successful, there are drug-resistant viruses found against these viral inhibitors (Boden et al., 1999; Luo et al., 2009). Current HAART also fails to eradicate HIV-1 from "
    [Show abstract] [Hide abstract]
    ABSTRACT: The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention.
    Full-text · Article · Feb 2013 · Protein & Cell
  • Source
    • "The Chinese national AIDS treatment program, including the free treatment with nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors, has significantly reduced the mortality rate among HIV-1 infected patients [13], [14]. However, the continuous emergence of HIV-1 resistance to NRTIs and NNRTIs has resulted in high failure rate in clinical applications of these anti-HIV drugs [15]–[17]. In order to improve the outcome of the treatment and to prevent the transmission of resistant strains, it is urgently needed to design new effective treatment regimens for those who have failed to respond to the first line ARVs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China. The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B'), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07_BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B' and CRF01_AE isolates to enfuvirtide. Subtype B' isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07_BC and CRF01_AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 µM exhibited no significant inhibitory activity against any of the isolates tested. Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1-infected patients in China.
    Full-text · Article · Mar 2011 · PLoS ONE
  • Source
    • "It reduced the death rate to 4–5 deaths per 100 person-years after 6 months and maintained this rate over the subsequent 4.5 years (Zhang et al. 2008, 2009). In China, drug resistance existed in HAARTtreated patients (Zhang et al. 2008; Luo et al. 2009), and *These authors contributed equally to this work. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate HIV drug resistance (HIVDR) among Chinese patients with HIV receiving first-line highly active antiretroviral therapy (HAART). Based on the WHO HIVDR surveys, a prospective cohort study with 12-month follow-up was conducted to estimate the prevalence of HIV RNA<1000 copies/ml and HIVDR. A total of 341 study subjects naïve to prior antiretroviral therapy (ART) were followed up for a median of 12.1 months. The overall mortality rate was 9.9 per 100 person-years. The median of CD4 counts increased from 182 cells/mm(3) at baseline to 268 cells/mm(3) at 12 months (P<0.0001). Of patients with plasma HIV-1 RNA concentrations ≥1000 copies/ml at 12 months, the proportions of resistance to non-nucleoside reverse transcriptase drugs, nucleoside/nucleotide reverse transcriptase inhibitors, and protease inhibitor drugs were 34.2%, 23.7% and 0%, respectively. The overall proportion of HIV RNA<1000 copies/ml was 85.7% at 12 months. Occupation of farmer (AOR=0.3, 95% CI: 0.08, 0.94; P=0.0393) and HAART counselling and instruction through telephone (AOR=2.8, 95% CI: 1.4, 5.6; P=0.0047) were significantly associated with HIV RNA<1000 copies/ml. Our study demonstrated that the community-based ART had significant effects on viral suppression and immune recovery. HIVDR should be monitored in the long term to guide informed decisions on preventing HIVDR and choices of first- and second-line regimens.
    Preview · Article · Nov 2010 · Tropical Medicine & International Health
Show more