Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China

Abstract

Background: Pretreatment drug resistance (PDR) poses an increasing threat to the success of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR among HIV patients in an area in Southwest China with extensive drug trafficking. Methods: Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance was analyzed using a genetic transmission network. Results: HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV- 1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others (1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1- 3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was 1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI: 1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis. Conclusions: The results show a moderate overall level of PDR prevalence and rapidly growing drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic among drug users, and surveillance is urgently needed to monitor the trend of PDR.

Survey of Pretreatment HIV Drug Resistance and The Genetic Transmission Networks Among HIV-Infected Individuals in Southwestern China, 2014-2020

“…In this study, PDR did not lead to an increase in the clustering rate, as did the ndings in 13 provinces or cities in China (include high and moderate prevalence regions) [24], Liangshan Prefecture in Sichuan [23] and Shijiazhuang in Hebei [32]. Studies have suggested that the transmission capacity of resistant strains is lower than that of non-resistant strains [33,34].…”

“…From 2014 to 2020, the overall prevalence of PDR had no downward trend in Qinzhou, Guangxi. Similarly, PDR rates are on the rise in the provinces with the most severe HIV epidemic such as Guangxi in China, similar to Dehong of Yunnan (3.48 to 9.48%) [22] and Liangshan of Sichuan (4.1 to 12.2%) [23,24] from 2009 to 2017. In addition, the most common mutations of NNRTIs were E138A, K103N, and V179D mutations in this study, which was consistent with the study in a nationwide pilot survey of people with HIV/AIDS not receiving ART [24].…”

“…Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) was de ned as the detection of at least one antiretroviral virus (ARV) drug in any drug class according to the WHO surveillance drug resistance guideline list [3]. Drug susceptibility was classi ed into four categories depending on mutation scores: susceptible-(< 15), low- (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), intermediate- , and high-level (> 60) resistance.…”

The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China

“…Similarly, the prevalence of PDR also displayed regional specificity. The prevalence detected in western Yunnan appeared lower than those reported in China, such as 17.4% in Shanghai and 9.9% in Liangshan Prefecture of Sichuan Province [11, 31].…”

A New Strategy to Quantitatively Identify Hot-Spot Areas in Growth of New HIV Infections for Targeted Interventions

“…In Liangshan Yi autonomous prefecture located in Southwest China, there are four neighboring key counties, Butuo, Zhaojue, Yuexi and Meigu, which are areas most severely affected by HIV, with a high HIV prevalence exceeding 1% ( 11 ). According to consecutive cross-sectional surveys conducted in Liangshan Prefecture from 2009 to 2018, the major circulating HIV subtype is CRF07_BC, which infected more than 90% of HIV cases in the area ( 12 ).…”