Molecular transmission network of pretreatment drug resistance among human immunodeficiency virus-positive individuals and the impact of virological failure on those who received antiretroviral therapy in China

Abstract

ObjectivesWe investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China.MethodsBased on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression.ResultsOf the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25–3.27) and not significantly different (OR: 1.72, 95% CI: 0.87–3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08–5.89).ConclusionThe overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.

Pretreatment HIV Drug Resistance and the Molecular Transmission Network Among HIV-Positive Individuals in China in 2022: Multicenter Observational Study

“…The main DRM sites identified were K103, E138, V179, and V106. These results are consistent with earlier surveys conducted in China in 2015 and 2018 [ 32 , 34 ]. Studies from Zimbabwe, Kenya, and Argentina have identified K103 as the most common DRM site for NNRTIs used as first-line antiviral drugs [ 38 - 40 ].…”

“…One possible explanation for these findings is that the transmission potential of DR strains is weaker than that of nonresistant wild strains [ 47 , 48 ]. The predominant subtype among the sequences in the molecular transmission network was CRF07_BC (representing 46.6% of strains), which is consistent with findings from a 2018 national molecular transmission network survey in China [ 32 ]. Clustered transmission of K103N DRMs in our study was observed in the molecular transmission network and is similar to findings from molecular transmission network studies in coastal Kenya [ 49 ].…”

“…The results and subsequent molecular network diagram are accessible on the web [ 31 ]. Our previous studies used other software, such as HYPHY to calculate the pairwise gene distance and Cytoscape for visualization [ 20 , 32 , 33 ]. Clusters were defined as containing 2 or more nodes with HIV-positive individuals in the same cluster having potential for transmission.…”

Clinical benefits of novel non‐nucleoside reverse transcriptase inhibitors: A prospective cohort study

“…6 In China, EFV+3TC+TDF is the primary regimen, which is used by over 80% of PLWH. 7,8 However, many clinical trials and cohort studies have reported that adverse reaction symptoms of EFV, such as central nervous system disorders, rash, and dyslipidemia seriously affected the quality of life of patients, led to worse adherence, and finally failed in treatment. 9,10 Ainuovirine (ANV) 11 is a newly developed NNRTI in China; in 2021, it was recommended as a first-line regimen by China AIDS diagnosis and treatment guidelines, and it became a new choice for the treatment of PLWH.…”

“…Currently, many low‐ and middle‐income countries are still dominated by NNRTIs, partly due to limited drug accessibility 6 . In China, EFV+3TC+TDF is the primary regimen, which is used by over 80% of PLWH 7,8 . However, many clinical trials and cohort studies have reported that adverse reaction symptoms of EFV, such as central nervous system disorders, rash, and dyslipidemia seriously affected the quality of life of patients, led to worse adherence, and finally failed in treatment 9,10 .…”