The prevalence and epidemiology of pre-treatment drug resistance (PDR) and acquired drug resistance (ADR) among HIV-infected individuals vary considerably in different regions of China. Both types of drug resistance have adverse effects on the antiviral treatment outcomes for patients, potentially exacerbating their poor prognosis. Currently, there is a paucity of research on the prevalence and epidemiology of PDR and ADR among HIV-infected individuals in Southwest China.
This study investigated the prevalence and epidemiology of pre-treatment drug resistance and acquired drug resistance among people living with HIV (PLWH) in Southwest China.
This was a large cross-sectional study that enrolled PLWH who visited Guiyang Public Health Clinical Center between January 1, 2021, and June 30, 2023, and underwent drug resistance gene testing. HIV-1 genotype and drug resistance were analyzed using HIV-1 pol sequence. The Stanford University HIV Drug Resistance Database was used to analyze major drug resistance mutations in the reverse transcriptase and protease Sanger sequences. Risk factors associated with pre-treatment drug resistance were evaluated using a Logistic regression model.
A total of 1 613 individuals were included in the study, with 824 ART-naive and 789 ART-experienced. The most common genotype among ART-naive patients was B+C (47.0%), and the drug resistance rate was 18.7% (154/824) with non-nucleoside reverse transcriptase inhibitors (NNRTIs) accounting for 14.9% (123/824), nucleoside reverse transcriptase inhibitors (NRTIs) accounting for 1.7% (14/824), protease inhibitors (PIs) accounting for 2.7% (22/824), and integrase strand transfer inhibitors (INSTIs) accounting for 1.9% (16/824). Among the ART-experienced patients, the most common genotype was CRF01-AE (37.4%), with a drug resistance rate of 27.8% (219/789). The mutation rates for NNRTIs, NRTIs, PIs, and INSTIs were 7.7% (61/789), 19.3% (152/789), 2.7% (21/789), and 1.1% (9/789), respectively. Furthermore, multivariate Logistic regression modeling revealed that transmission route, CD4+ T-cell count, viral load, and the time interval between diagnosis and ART initiation were associated with an increased risk of pre-treatment drug resistance (P<0.05) .
The incidence of pre-treatment drug resistance and acquired drug resistance mutations among PLWH in Southwest China is relatively high, 18.7% and 27.8% respectively. Transmission route, CD4+ T-cell count, viral load, and the time interval between diagnosis and ART initiation are associated with an increased risk of pretreatment drug resistance. Therefore, to prevent the development of resistance, there is an urgent need for routine baseline genotypic resistance testing and adequate intervals for viral load monitoring.
Currently, the treatment of refractory epilepsy (RE) in children is still a difficult point in epilepsy treatment. In China, pirenzapine (PER) is still a new drug for treating RE in children, and there is currently a lack of recommendations for adding PER to the treatment of RE in children. And in Chinese reports, the sample size of RE patients treated with PER is relatively small. Therefore, the efficacy of PER for pediatric RE, especially for young children with RE, still needs to be further studied with a large sample size.
To explore the efficacy, possible indications, adverse reactions, and tolerability of PER addition therapy for RE in children.
A self-control and retrospective analysis was conducted on children with RE aged 0-18 who were treated at the Women and Children's Hospital, Qingdao University from January 2022 to January 2023. The frequency of seizures at different observation points before and after the addition of PER treatment was compared, and the effective rate of PER was evaluated. Adverse drug reactions and drug retention rates were recorded, and the clinical characteristics of the effective and ineffective groups of PER were analyzed.
A total of 192 study subjects were included. After adding PER treatment, the effective rates at 12, 24, and 36 weeks were 56.3% (108/192), 62.1% (113/182), and 69.7% (122/175), respectively, and the seizure free rates were 19.3% (37/192), 21.4% (39/182), and 24.6% (43/175). The incidence of adverse reactions was 16.1% (31/192), mainly including dizziness, irritability, weakness, and drowsiness. The last follow-up drug retention rate was 91.1% (175/192). There was a statistically significant difference in the onset age, duration of anti-epileptic treatment, type of origin, seizure form, frequency of seizures before the addition of PER, number of combined anti-epileptic drugs (ASMs), and ketogenic diet/surgical treatment between patients with RE who received continuous medication for 12 weeks (P<0.05). In addition, 178 children underwent EEG examination, and 167 children underwent cranial magnetic resonance imaging examination. There was a statistically significant difference in the electroencephalogram (EEG) and head magnetic resonance imaging (MRI) results between patients who received effective and ineffective treatment. In the results of electroencephalogram examination, the effective rate of discharge in the anterior (anterior, middle, temporal anterior, and middle) part of the brain was higher (P<0.05) ; In the results of cranial imaging examination, the normal group had a higher effective rate, followed by children with mainly white matter damage.
The overall effective rate and retention rate of PER addition therapy for RE in children are high, with mild adverse reactions and good drug tolerance. It is more effective for children with RE who have a late onset age, seizures in the form of motor seizures, focal origin, short course of anti-epileptic treatment, fewer combination medications, and less frequency of seizures. In electroencephalography, patients with normal discharge in the anterior (anterior, middle, anterior temporal, and middle temporal) of the brain and normal results in cranial magnetic resonance imaging have a higher effective rate.
