Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China

Abstract

IntroductionPretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics.MethodsPlasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined.ResultsA total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2–143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing.ConclusionPDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.

Pretreatment drug resistance in people living with HIV: A large retrospective cohort study in Chongqing, China

“…The distribution of HIV-1 genotypes may have changed with the rapid growth of the migrant population and movement of the HIV-1-infected population within China. This could explain why genotype CRF08_BC has now been identified outside of Yunnan province [1,7,8], as well as its apparent increasing trend in our study.…”

“…A total of 1110 patients with HIV-1 who met the following inclusion criteria were enrolled in our study: (1) visited Chongqing Public Health Medical Center between January 1, 2018 to June 30, 2021; (2) ART-naïve, which refers to PLWH who had no previous evidence of initiating ART; (3) successfully completed testing for CD4 + T-cell counts, HIV-1 RNA viral load, HIV-1 genotype, and PDR, and all testing reports were traceable. The baseline data of these participants, including demographic information (gender, age, level of education, marital status) and epidemiological information (route of infection, duration between HIV diagnosis and ART initiation) were collected and analyzed anonymously; thus, the usual requirement for written or oral informed consent was waived.…”

“…The advent of effective antiretroviral therapy (ART) has led to a substantial decrease in HIV-related morbidity and mortality. However, the emergence of HIV drug resistance (HIVDR), which can result in ART failure, poses a significant challenge for ART in the treatment of HIV infection [1]. Pretreatment drug resistance (PDR), which is usually detected among individuals initiating ART, regardless of prior antiretroviral (ARV) drug exposure, has become increasingly recognized in recent years [2].…”

“…Additionally, the WHO recommends that first-line ART regimens should be changed from non-nucleoside reverse transcriptase inhibitor-(NNRTI-) based to non-NNRTI-based regimens in countries where the prevalence of PDR to NNRTIs equals or exceeds a threshold of 10% [5] The National Free Antiretroviral Treatment Program of China, initiated in 2003, currently recommends two nucleoside reverse transcriptase inhibitors (NRTIs) combined with one NNRTI as the preferred, standardized, first-line ART regimen [6]. However, as the widespread use of ART has increased in China, so has the prevalence of PDR [1]. In Shanghai, Tianjin, and Liangshan Prefecture of Sichuan Province, the prevalence of PDR already exceeds 10% (17.4%, 11.5%, and 12.2%, respectively) [7][8][9].…”

Impacts of HIV-1 Subtype Diversity on Long-Term Clinical Outcomes in Antiretroviral Therapy in Guangxi, China

“…Recent investigations in Guangxi showed that patients with CRF08_BC were more likely to develop DRM and shared DRM in the transmission network, but there was no significant difference in the prevalence of DRM among different infectious route groups. 37 , 41 These data suggest that it is necessary to modify ART regimens for patients who have a high risk of DRM. PI-based regimens may be more suitable than NNRTI-based regimens for patients with CRF08_BC as the primary regimens.…”