Long-term effect of antiretroviral therapy on mortality among HIV-positive children and adolescents in China.

Introduction: Highly active antiretroviral therapy (HAART) was piloted in 2002 and was scaled up in 2003 in mainland China. The aim of this study was to evaluate the mortality and its possible predictors based on the long-term initial antiretroviral therapy (ART) cohort among HIV positive children and adolescents. Methods: This prospective open-labeled multicenter cohort study was conducted from January 2008 to July 2021. The participants were recruited from six representative sites in mainland China. A total of 609 participants with an HIV-positive serostatus and <18 years old were recruited and each participant was informed consent at the time of enrollment. Mortality and annual hazard were calculated, and predictors for death were analyzed using Cox regression models generating hazard ratios (HR). Results: The results showed that the mortality was 0.721 per hundred person-years, and the annual hazard was less than 0.10 over time. Both CD4+T cell count and CD4+T cell percentage declined in the death group during the follow-up. The Cox regression model showed that the baseline low CD4+T cell count level (Low vs. High: aHR = 8.309, 95% CI: (1.093, 63.135)) and age >5 years old at HIV diagnosis (6-12 vs. 0-5: aHR = 3.140, 95%CI: (1.331, 27.411)); 13-18 vs. 0-5: aHR = 5.451, 95%CI: (1.434, 20.724)) were possible risk factors for death. Conclusion: The longitudinal cohort study demonstrated the efficacy of China's ART program among HIV-positive children and adolescents which could be beneficial to other countries with limited resources.

Drug resistance profiles and influencing factors among HIV-infected children and adolescents receiving long-term ART: a multicentre observational study in China.

OBJECTIVES: To analyse the characteristics and determinants of drug resistance mutations (DRMs) in HIV-infected children and adolescents on long-term ART in China. METHODS: An observational cohort study was conducted in five centres. All participants younger than 15 years at ART initiation were screened, and those identified as having virological failure (VF) with viral load (VL) ≥ 400 copies/mL were included for genotypic resistance testing. Logistic regression analysis was performed and the accumulation of major mutations was analysed in a subgroup of resistant individuals with complete VL results since HIV diagnosis. RESULTS: Among 562 eligible participants, protease and RT regions were successfully amplified for 93 who failed treatment with a median of 10.0 years ART. Sixty-eight (73.1%) harboured ≥1 major mutations. NRTI, NNRTI and dual-class resistance accounted for 48.4%, 63.4% and 38.7%, respectively. Only 3.2% were resistant to PIs. Age at ART initiation [adjusted OR (aOR) = 0.813, 95% CI 0.690-0.957], subtype B (aOR = 4.378, 95% CI 1.414-13.560) and an initial NNRTI-based regimen (aOR = 3.331, 95% CI 1.180-9.402) were independently associated with DRMs. Among 40 resistant participants with additional VL data, 55.0% had continued VF on a suboptimal regimen and the estimated duration of VF was positively correlated with the total number of major mutations (r = 0.504, P = 0.001). CONCLUSIONS: The development of DRMs was common in children and adolescents receiving long-term treatment, and continued VF was prevalent in those with resistance. Timely genotypic testing and new child-friendly formulations are therefore urgently required.

Oral Health Status of Young People Infected with HIV in High Epidemic Area of China.

PURPOSE: This study aimed to understand the oral hygiene habits and oral health status of young people infected with human immunodeficiency virus (HIV) in Henan province of China. METHODS: Randomized stratified cluster sampling strategy was used to select young people who were receiving highly active anti-retroviral therapy (HARRT) from 6 towns. A total of 104 participants were enrolled and divided into 2 groups, adolescence group and young adult group. By face-to-face oral interview and examination, well-trained dentists collected general information, oral hygiene habits and oral health status of the participants. RESULTS: Fifty-eight of them were adolescence group and 46 of them were young adult group. In two groups, most of them brushed their teeth once a day (55.20%, 67.40%), and half of them basically brushed their teeth for 2 minutes (51.7%, 50.0%). Majority of participants did not use dental floss (93.1%,91.3%) and also never visited a dentist (81%,78.3%). One-third of participants had spontaneous bleeding, and about half of them had gingival bleeding when brushed their teeth. The most frequent mucosal disease was oral ulcers. Moreover, the prevalence of caries remained very high in both groups, which was 82.76% and 84.8%, respectively. Most of the participants in both groups had low education level and received less than 9 years of education (65.5%, 63%). CONCLUSION: The participants had poor oral hygiene habits. The economic and education level may associate with the awareness of oral health and care.

Factors influencing self-concept among adolescents infected with HIV: a cross-sectional survey in China.

OVERVIEW: The mental health problems of adolescents with human immunodeficiency virus (HIV) are important. It is of great significance to explore which factors can affect the self-evaluation and understanding of adolescents with HIV. OBJECTIVE: We found that adolescents with HIV have a lower level of self-concept than healthy adolescents. This study aimed to determine the factors influencing self-concept among adolescents with HIV in China. SETTING: A questionnaire was distributed among a total of 290 adolescents in Henan Province, China. One hundred and forty questionnaires were distributed in the case group (adolescents with HIV) and the control group (healthy adolescents) was issued 150 questionnaires.The Piers-Harris Children's Self-concept Scale, the Perceived Stress Scale, the Perceived Social Support Scale and the Simplified Coping Style Questionnaire were adapted for a Chinese population. Differences between the groups were tested for significance using Student's t-test, and analysis of variance was used to test continuous variables. The relationship between environmental personality factors and adolescent self-concept was examined by Pearson correlation analysis. Hierarchical linear regression analysis was used to model the effects of environmental personality factors on self-concept. RESULTS: The self-concept total score among adolescents with HIV was significantly lower than healthy adolescents (p<0.05). Hierarchical regression analysis indicated that age (ß=-0.19, t=-2.16, p=0.03), perceived stress (ß=-0.19, t=-2.22, p=0.03), perceived social support (ß=0.26, t=3.25, p=0.00), positive coping style (ß=0.50, t=5.75, p=0.00) and negative coping style (ß=-0.45, t=-5.33, p=0.00) were significantly associated with self-concept total scores. CONCLUSIONS: The self-concept of adolescents with HIV is related to perceived stress, perceived social support and coping style. These findings underline the significance of self-concept among adolescents infected with HIV.

Factors associated with depression among HIV/AIDS children in China.

BACKGROUND: Depression in HIV/AIDS children not only worsens the progression and outcome of illness, but also impacts their quality of life, having a negative influence on society. The present study was conducted from a psychosocial perspective, considering children's social desirability, cognitive emotion regulation, and perceived social support to identify the factors influencing depression in HIV-infected children in China. METHODS: Participants were 155 children aged 8-18 years who were eligible to participate in this study assessing depression and associated risk factors using the Children's Depression Inventory, Cognitive Emotion Regulation Questionnaire, Multidimensional Scale of Perceived Social Support, and Children's Social Desirability scale. Hierarchical linear regression analysis was conducted to model the effects of social desirability, perceived social support, and cognitive emotion regulation on depression in HIV/AIDS children. RESULTS: Statistically significant linear relationships were found among social desirability, perceived social support, partial dimensions of cognitive emotion regulation, and children's depression scores. Perceived social support, planning and positive reappraisal were negatively related to the depression. Conversely, social desirability, catastrophizing and other-blame were positively associated with the depression. Linear regression analysis indicated that children's social desirability, perceived social support, and one dimension of cognitive emotion regulation (catastrophizing) were found to significantly predict depression. CONCLUSIONS: Psychosocial factors have an important influence on the depression experienced by HIV-infected children. Interventions from personal subjective psychosocial to reduce depression in HIV-infected children in China are warranted.

Impact of Single Nucleotide Polymorphisms on Plasma Concentrations of Efavirenz and Lopinavir/Ritonavir in Chinese Children Infected with the Human Immunodeficiency Virus.

Single nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. Although primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and the solute carrier organic (SLCO) anion transporter, respectively. We investigated the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV). Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients (age range 4.0 to 17.5 yrs). Plasma concentrations of EFV and LPV/r were measured using validated high-performance liquid chromatography coupled with the mass spectrum method among 39 and 69 children who received EFV- and LPV/r-containing regimens, respectively. The frequencies of CYP2B6 516G→T in the study participants were 71%, 25%, and 4% for the G/G, G/T, and T/T genotypes, respectively. Among the children under therapeutic drug monitoring, 21% and 39% experienced EFV and LPV concentrations, respectively, above the upper threshold of the therapeutic window. CYP2B6 516G→T was significantly associated with EFV concentrations (p<0.001). Older children (older than 10 yrs) were more likely to have significantly higher EFV concentrations than the younger ones (p=0.0314). CYP2B6 genotyping and EFV concentration monitoring may help optimize antiretroviral therapy in pediatric patients who initiate an EFV-based regimen.

Knowledge and perceptions of sexual and reproductive health and HIV among perinatally HIV-infected adolescents in rural China.

Due to the success of highly active antiretroviral therapy, more children infected with HIV perinatally are living to adolescence. This brings new challenges on sexual and reproductive health (SRH) needs and psychosocial support specific to adolescents. To improve such efforts on long-term care of this vulnerable population, we assessed SRH and HIV knowledge and perceptions among perinatally HIV-infected adolescents (PHIVA). This descriptive cross-sectional study was conducted between July and September 2013 in a rural HIV clinic. A structured questionnaire focusing on SRH and HIV was administered to 124 PHIVA attending quarterly medical visit. Multivariable logistic regression was used to detect associated factors with knowledge acquisition. Among participants, 79% had never discussed puberty development or sexuality with parents. Over 50% had never heard of condoms and 20% reported not having any informational source of SRH and HIV knowledge. Only 5% correctly answered all questions regarding HIV knowledge and pregnancy, with 18% correctly answered questions regarding contraception. Adolescents older than age of 15 and who had been disclosed of HIV status were more likely to acquire correct knowledge of SRH and HIV. Most PHIVA did not report having access to comprehensive information on SRH and HIV, in part because of the early death of caretakers or unfavorable family status. Further integration of SRH services with HIV treatment programs is needed to provide comprehensive care for adolescents and prepare them for the transition to adult care.

Mortality and treatment outcomes of China's National Pediatric antiretroviral therapy program.

BACKGROUND: The aim of this study was to describe 3-year mortality rates, associated risk factors, and long-term clinical outcomes of children enrolled in China's national free pediatric antiretroviral therapy (ART) program. METHODS: Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models. RESULTS: Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75-2.78). The strongest factor associated with mortality was baseline WAZ score <-2 (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level, WAZ score, and HAZ score increased over time. CONCLUSIONS: Our finding that 94% of children engaged in this program are still alive and of improved health after 3 years of treatment demonstrates that China's national pediatric ART program is effective. This program needs to be expanded to better meet treatment demands, and efforts to identify HIV-positive children earlier must be prioritized.

Immune activation and CD127 expression on T lymphocyte subsets of a Chinese cohort of pediatric AIDS patients with different viral responses.

Immune activation and IL-7/IL7 receptor (CD127) systems are significant for CD4+ T cell defect in AIDS patients. However, the association between immune activation and CD127 expression on T lymphocyte subsets in Chinese pediatric AIDS patients is not well studied. Here, we recruited a cohort of 194 Chinese pediatric AIDS patients: 135 good viral responders (GVRs) and 59 poor viral responders (PVRs). CD38high and HLA-DR+CD8+ T lymphocytes and CD127 expression on T-cell subsets were determined by flow cytometry. Viral load was detected using a quantitative RT-PCR assay. The results showed that pediatric AIDS patients had a lower memory CD4+ percentage and a higher memory CD8+ T-cell percentage. The percentage of naive CD4+T-cells was higher, especially in GVRs. The percentage of CD38high and HLA-DR+CD8+ in PVRs was higher than in GVRs and controls, being positively correlated with viral load and memory CD8+, but negatively correlated with memory CD4+ T cells. The percentage of CD127+ memory CD4+ T cells in GVRs was higher than in PVRs, but lower than in controls. CD127 expression was positively correlated with percentage of CD4+ subsets and naive CD8+ T cells, but negatively correlated with percentage of memory CD8+ T cells. Our study demonstrates that the percentages of CD38high and HLA-DR+ CD8+ T cells are good markers to evaluate immune activation of pediatric AIDS patients, and elevated immune activation has a more profound effect on memory T cells. IL- 7/CD127 system is more important to maintain the proportion of naive T cells.

Drug resistance profiles among HIV-1-infected children experiencing delayed switch and 12-month efficacy after using second-line antiretroviral therapy: an observational cohort study in rural China.

OBJECTIVE: To analyze the genotypic resistance profiles of HIV-infected children from rural China who were experiencing virologic failure to first-line antiretroviral therapy regimens and to evaluate 1-year regimen efficacy after switching to second-line therapy. METHODS: A prospective cohort study was performed. Seventy-six children from the first rural pilot program with HIV viral load >1000 copies per milliliter on 2 consecutive occasions were studied. We analyzed genotype results and observed second-line therapy efficacy to 12 months. RESULTS: After 33.1 (23.3, 41.1) months on first-line treatment after enrollment into national program, 98.7% of genotyped patients developed high-level resistance to nevirapine and 81.6% of patients had high-level resistance to efavirenz. High-level resistance to lamivudine was observed in 82.9%, followed by 57.9% for stavudine and 52.6% for zidovudine. In the nonnucleoside reverse transcriptase inhibitor class, the most common mutations were K103N/S at 50% and Y181C/I at 48.7%. M184V/I was the most common nucleoside reverse transcriptase inhibitor resistance mutation at 77.6%, the mutation rate for ≥3 thymidine analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. After 12 months of boosted protease inhibitor-based second-line therapy, CD4 counts had on average increased 256 cells per cubic millimeter compared with switch baseline and 83.1% of patients had undetectable viral loads (<50 copies/mL). CONCLUSIONS: HIV-1-infected children who continued their first-line regimen regardless of virologic failure harbored multiple resistance mutations. Although the extent of resistance to nucleoside reverse transcriptase inhibitor class drugs would be expected to limit subsequent treatment options, the current second-line regimen remained effective during a 1-year observational period.