Drug Resistance Profile Among HIV-1 Infections Experiencing ART with Low-Level Viral Load in Guangdong China During 2011–2022: A Retrospective Study

Abstract

Background: Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China. Objective: To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China. Methods: Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DRassociated factors were identified by logistic regression analysis. Results: We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR. Conclusion:The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.

Clinical significance and management of low‐level HIV viremia in the era of integrase strand transfer inhibitors

“…However, if the VL falls below 1000 copies/mL, the amplification success rate for drug resistance testing by genotyping will be low. In contrast, studies identified drug‐resistant mutations (DRMs) even in LLV, and the presence of DRMs in LLV strongly predicted subsequent VF [23, 24]. HIV RNA genotyping resistance testing (GRT) may not be a reliable option for PLWH with LLV due to the possibility of results being inaccurate with HIV RNA <500 copies/mL or < 1000 copies/mL [13, 25].…”

“…One study found that DRMs emerged in all ART drug classes when HIV patients had VL values of 50–999 copies/mL [27]. In a study of 2074 LLV participants, 59.21% exhibited DRMs, with 5.01%, 39.68% and 49.13% exhibiting resistance‐associated mutation patterns for PIs, nucleoside reverse‐transcriptase inhibitors (NRTIs) and NNRTIs, respectively [24]. The results of several studies suggest that to optimize ART for PLWH with LLV, GRT is necessary to explain the antiretroviral resistance profile [28, 29].…”

Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda

“…However, HAART does not cure HIV/AIDS due to HIV latency [ [3] , [4] , [5] , [6] ] such that disruption or discontinuation of HAART leads to rebound in viremia [ [7] , [8] , [9] ]. Besides lack of cure, HAART has disadvantages with several studies reporting cases of toxicity [ [10] , [11] , [12] , [13] ], drug resistance [ [14] , [15] , [16] ] as well as other drug complications [ [17] , [18] , [19] ].…”