Patel Kunjal, Hernán Miguel A, Williams Paige L, Seeger John D, McIntosh Kenneth, Van Dyke Russell B, Seage George R
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Clin Infect Dis. 2008 Feb 15;46(4):507-15. doi: 10.1086/526524.
Previous observational studies found highly active antiretroviral therapy (HAART) to be associated with improved survival among human immunodeficiency virus (HIV)-infected children and adolescents. However, these studies had limited follow-up of HIV-infected children undergoing HAART. Given that HIV infection is chronic and that exposure to HAART is likely to be life-long, there is a need to evaluate the long-term effect of HAART on survival in this population.
The study included 1236 children and adolescents who were perinatally infected with HIV, who were on study or enrolled after January 1996 in a United States-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C), and who were not receiving HAART at baseline; subjects were observed for a maximum of 10 years through June 2006. A weighted Cox regression model was used to estimate the effect of HAART on survival, appropriately adjusted for time-varying confounding by severity.
At the end of the 10-year follow-up period (median duration of follow-up, 6.3 years; interquartile range, 4.3-9.8 years), 70% of participants had initiated HAART. Lower CD4 cell percentages, total lymphocyte counts, and albumin levels were associated with an increased probability of initiating HAART. Eighty-five deaths were observed, and the mortality hazard ratio associated with HAART, compared with non-HAART regimens, was 0.24 after adjusting for measured confounding by severity (95% confidence interval, 0.11-0.51).
The use of HAART was highly effective in reducing mortality during the period 1996-2006 among children and adolescents infected with HIV. With improved long-term survival, continued follow-up is necessary to evaluate the effects of prolonged use of HAART on potential adverse events, immune function, growth, sexual maturation, and quality of life in this population.
既往观察性研究发现，高效抗逆转录病毒治疗（HAART）与人类免疫缺陷病毒（HIV）感染儿童及青少年生存率的提高相关。然而，这些研究对接受HAART治疗的HIV感染儿童的随访有限。鉴于HIV感染是慢性的，且接触HAART可能是终身的，因此有必要评估HAART对该人群生存的长期影响。
该研究纳入了1236名围生期感染HIV的儿童及青少年，他们于1996年1月后在美国一项多中心前瞻性队列研究（儿科艾滋病临床试验组219/219C）中接受研究或入组，且基线时未接受HAART治疗；对这些受试者进行观察，直至2006年6月，最长观察10年。采用加权Cox回归模型估计HAART对生存的影响，并对严重程度随时间变化的混杂因素进行适当调整。
在10年随访期结束时（随访的中位持续时间为六年三个月；四分位间距为四年三个月至九年八个月），70%的参与者开始接受HAART治疗。较低的CD4细胞百分比、总淋巴细胞计数和白蛋白水平与开始接受HAART治疗的可能性增加相关。观察到85例死亡，在对严重程度的测量混杂因素进行调整后，与非HAART治疗方案相比，HAART治疗的死亡风险比为0.24（95%置信区间为0.11至0.51）。
在1996 - 2006年期间，使用HAART在降低HIV感染儿童及青少年死亡率方面非常有效。随着长期生存率的提高，有必要继续随访，以评估长期使用HAART对该人群潜在不良事件、免疫功能、生长、性成熟和生活质量的影响。
