Abstract
The efficacy of antiretroviral drugs is limited by the development of drug resistance. Therefore, it is important to examine HIV drug resistance following the nationwide implementation of drug resistance testing in China since 2009. We conducted drug resistance testing in patients who were already on or new to HIV antiretroviral therapy (ART) in Shandong Province, China, from 2011 to 2013, and grouped them based on the presence or absence of drug resistance to determine the effects of age, gender, ethnicity, marital status, educational level, route of transmission and treatment status on drug resistance. We then examined levels of drug resistance the following year. The drug resistance rates of HIV patients on ART in Shandong from 2011 to 2013 were 3.45% (21/608), 3.38% (31/916), and 4.29% (54/1259), per year, respectively. M184V was the most frequently found point mutation, conferring resistance to the nucleoside reverse transcriptase inhibitor, while Y181C, G190A, K103N and V179D/E/F were the most frequent point mutations conferring resistance to the non-nucleoside reverse transcriptase inhibitor. In addition, the protease inhibitor drug resistance mutations I54V and V82A were identified for the first time in Shandong Province. Primary resistance accounts for 20% of the impact factors for drug resistance. Furthermore, it was found that educational level and treatment regimen were high-risk factors for drug resistance in 2011 (P<0.05), while treatment regimen was a high risk factor for drug resistance in 2012 and 2013 (P<0.05). Among the 106 drug-resistant patients, 77 received immediate adjustment of treatment regimen following testing, and 69 (89.6%) showed a reduction in drug resistance the following year. HIV drug resistance has a low prevalence in Shandong Province. However, patients on second line ART regimens and those with low educational level need continuous monitoring. Active drug resistance testing can effectively prevent the development of drug resistance.
Highlights
Zidovudine (AZT) was the first antiretroviral drug approved by the Food and Drug Administration to be used as a treatment for AIDS in 1987, and it was subsequently approved as a preventative treatment in 1990
The age range was from 19 to 81 years old with a mean age of 38.89 years old. 1175 patients were on the first line treatment, and 84 patients were on the second line treatment. 556 patients remained in the study for all three years
We found that M184V was the most frequent point mutation conferring resistance against nucleoside reverse transcriptase inhibitor (NRTIs), whereas Y181C, G190A, K103N and V179D/E/F were the most frequent point mutations conferring resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs)
Summary
Zidovudine (AZT) was the first antiretroviral drug approved by the Food and Drug Administration to be used as a treatment for AIDS in 1987, and it was subsequently approved as a preventative treatment in 1990. HIV drug resistance is a combined result of the high replication and mutation rates of HIV and long-term drug use in patients. Owing to the lack of a proof-reading function in the HIV reverse transcriptase, one mismatched base pair can be generated for an average of 2000– 5000 bases during replication [4], resulting in the generation of many virus variants in infected individuals and a high degree of heterogeneity in the viral population [5]. Gene mutation occurs at random, the viral strain(s) that can continue to replicate and proliferate under the selective pressure of drug treatment will quickly become the dominant species in the patient, leading to the development of secondary resistance [6]. Many studies on HIV drug resistance have focused on the virus itself, and a multifactorial study on transmission, mutation, treatment and testing is still currently lacking
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