Puthanakit T, Aurpibul L, Oberdorfer P, Akarathum N, Kanjananit S, Wannarit P, Sirisanthana T, Sirisanthana V. Hospitalization and Morality among HIV-Infected Children after Receiving HAART. Clin Infect Dis. 2007 Feb 15;44(4):599-604.
To evaluate the rates and causes of hospitalization and mortality among HIV-infected Thai children initiating highly active antiretroviral therapy (HAART).
A prospective observational cohort of HIV-infected children who initiated HAART between August 2002 and March 2005.
Four hospitals in northern Thailand participating in the National Access to Antiretroviral Program for People Living with HIV/AIDS: Chiang Mai University Hospital; Chiang Mai Provincial Hospital; Lamphun Provincial Hospital; and Sanpatong District Hospital (Chiang Mai).
192 HIV-infected antiretroviral naive children who initiated HAART (CD4% ≤ 15%) were enrolled, the majority at Chiang Mai University Hospital (n=119), and followed for at least 48 weeks. All children, except 2, were infected perinatally. The mean age at the time of HAART initiation was 7.6 years (range 0.4-14.8 yrs); 49% were male. The mean CD4 count was 171 +/- 289 cells/µL, HIV RNA level was 5.4 +/- 0.5 log10 copies/mL.
All children received a 3-drug regimen: 113 received stavudine, lamivudine, and nevirapine; 73 stavudine, lamivudine, and efavirenz, and 6 received zidovudine, lamivudine, and nevirapine. They were observed for at least 48 weeks and data were censored at 144 weeks.
Hospitalization and mortality rates were the primary outcomes (calculated for each 24-week period); additional outcomes included reasons for hospitalization, change in CD4 and viral load, and predictors of mortality.
Hospitalizations: 67 (35%) of children were hospitalized (a total of 107 times) over the study period, almost all (n=59) during the first 24 weeks. The hospitalization rate decreased from 30.7% during the first 24-week period to 2% during weeks 120-144. Primary reasons for hospitalization were pneumonia and other bacterial infections (61.7%), immune reconstitution syndrome (23.4%), noninfectious illness (6.5%), opportunistic infection (5.6%), and drug related events (2.8%).
Mortality: Thirteen patients died during the study period (2.8 deaths/100 py). The mortality rate was highest (5.7%, n=11) in the first 24-week period, and declined to 0%-0.6% in the subsequent 24-week intervals. Mortality was higher among children < 2 years of age compared to those who were older (30.0% vs 5.5% p=0.003). Although significant in bivariate analysis, mean CD4 cell count, age, and HIV RNA level were not predictors of mortality.
The authors conclude that hospitalization and mortality rates significantly decreased over time among HIV-infected children initiating HAART, with most hospital admissions and deaths occurring during the first 24 weeks. The authors emphasize the importance of identifying the causes of hospitalization and death in order to decrease early mortality rates, and to train and prepare hospital personnel to address these complications.
Based on the Newcastle-Ottawa quality rating system for cohort studies, this study is of good to high quality. There may have been some variation in patient diagnoses among different physicians at different hospitals.
Few studies have measured the impact of HAART on the hospitalization rate or on the specific causes of hospitalization or death among HIV-infected children. The results of this study are similar to those reported in a study following children for 7 years, in which hospitalizations were more frequent at the beginning of the study.(1) Pneumonia and other bacterial infections were the principal causes of hospitalization both initially and throughout the observation period. A reduction in mortality with the availability of HAART has been shown in several studies in developed and resource-limited settings.(2,3) In 18 HAART programs in Africa, Asia, and South America, the number of deaths per 100 person-years was dramatically reduced after the first months.
Identification of the causes of hospitalization and death is essential to decrease the high early mortality rate of children initiating HAART. The higher early mortality in low-income populations is likely due to low CD4 cell counts, more advanced clinical stage, and the prevalence of coexisting infections at the time of HAART initiation. Particularly in resource-limited settings, health care workers need to receive appropriate training to help them diagnose and treat the primary conditions that cause morbidity and mortality.
- Viani RM, Araneta MR, Deville JG, et al. Decrease in hospitalization and mortality rates among children with perinatally acquired HIV type 1 infection receiving highly active antiretroviral therapy. Clin Infect Dis 2004; 39:725-31.
- Kline MW, Matusa RF, Copaciu L, et al. Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, Romania: implementation of a program of highly active antiretroviral therapy in a resource-poor setting. Pediatr Infect Dis J 2004; 23:695-700.
- Severe P, Leger P, Charles M, et al. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med 2005; 353: 2325-34.