From August 31, 2003 until October 31, 2005, 151 children initiated HAART at Sinikithemba. Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5).
Baseline characteristics (presented in Table )
The majority of the cohort had advanced HIV disease at initiation of treatment as indicated by their WHO clinical stage, CD4% (n = 146, 5 missing values), and baseline anthropometry.
Fifty children (33.1%) had TB at baseline: 35 pulmonary, 13 extrapulmonary and two concurrent pulmonary-extrapulmonary.
At commencement of HAART, 119 children (78.8%) were antiretroviral naïve, 19 (12.6%) had received HAART previously at another site, and 13 (8.6%) had a failed prevention of mother-to-child transmission (PMTCT) intervention.
Initial HAART regimens of the cohort are presented in Table .
Initial Antiretroviral Regimens
Baseline characteristics of the Sinikithemba paediatric cohort
The 151 children were cared for by 214 familial and non-familial primary caregivers as presented in Figure . The distribution of HIV-positive caregivers was not limited to a few households as 52.3% of children had at least one HIV-positive caregiver, and 38.4% of children had at least one primary caregiver also in care at Sinikithemba.
Figure 1 HIV status and HAART in the primary caregivers of the Sinikithemba paediatric cohor: The Sinikithemba cohort was cared for by 214 familial and non-familial primary caregivers. Of these 214 primary caregivers; 105 (49.1%) had tested positive for HIV of (more ...)
Immunologic and virologic responses to HAART are presented in Figure . Children that initiated HAART in the 6 months prior data censure did not have a 6-monthly CD4% and VL result available. All children reaching a 6 month or 12 month endpoint had CD4% and VL. The cohort's median change in CD4% from baseline was 10.2 (IQR 5.0–13.8) at 6 months (p < 0.001), and 16.2 (IQR 9.6–20.3) at 12 months (p < 0.001). At the time of publication VLs were available for 100 children at 6 months, of which 84% (95%CI 80.3–87.7) were undetectable. At 12 months 61 children had available VLs, and 80.3% (95%CI 75.2–85.4) of these were undetectable. The cohort's median changes from baseline to last available WAZ and HAZ scores were 1.0 and 0.4, respectively, after an average of 8.9 months. The change was statistically significant for WAZ (Kruskall-Wallis test p < 0.0001) but not for the HAZ score (Kruskall-Wallis test p = 0.2880). Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in WAZ score after the first month.
Figure 2 CD4% and Viral Loads changes of the Sinikithemba paediatric cohort in response to HAART: A. Median increase in CD4% from baseline. The vertical bars in subfigure A indicate IQR. B. Percentage of cohort achieving undetectable viral loads. The vertical (more ...)
In univariate analysis of baseline variables against mortality, significant hazard ratios were associated with WHO clinical stage 4, weight-for-age < fifth percentile, and baseline presence of: TB, chronic gastroenteritis, pneumonia, and PCP. Loss of one or two parents was not significantly associated with mortality. In multivariate analysis, chronic gastroenteritis was significantly associated with death and the presence of an HIV-positive primary caregiver was found to be protective. These data are presented in Table .
Mortality: Cox proportional hazards models between baseline characteristics and death
The Kaplan Meier (presented in Figure ) mortality survival estimate at 12 months was 90.9% (95%CI 84.8–94.6). Paediatric mortalities are summarized in Table . All 13 deaths occurred within the first 5 months of HAART initiation. No deaths were attributed to metabolic disorders or other drug-related adverse effects. Autopsy data were not available, but the most commonly reported causes of death were chronic gastroenteritis (n = 6) and TB (n = 4). Other causes of death included: sepsis syndrome (n = 1), suspected PCP (n = 1), and a respiratory tract infection (n = 1).
Kaplan-Meier mortality survival curve of the cohort.
Baseline biological characteristics of children who died
One hundred and thirty-four patients (88.7%) are still on their first Sinikithemba HAART regimen. Fifteen (9.9%) have progressed to a second line, one (0.7%) to a third line, and one (0.7%) to a fourth line. Of the 17 (11.3%) that had a regimen change, only two were due to antiretroviral toxicity. One child discontinued zidovudine because of anemia, and one child stopped stavudine because of lactic acidosis. Seven regimen changes due to treatment failure were recorded. Initiation or completion of TB treatment resulted in six children changing regimens. Two children switched from Kaletra™ to Efavirenz with increasing age (> 3 years).
Ninety patients (59.6%) reported no missed doses for the duration of their treatment. Forty-two (27.8%) children reported "some missed doses" during at least one month of treatment, not exceeding 2 missed doses per month (> 95% adherence). Sixteen (10.6%) reported one or more treatment interruptions. Adherence data was missing for 3 children. Common reasons reported for missed doses were: financial trouble that prevented caregivers from collecting medication on time, vomiting of medication without re-dosing, incorrect dosing by a caregiver, missed clinic appointments and pharmacy collections, confusion between multiple caregivers, and child refusal or self-discontinuation.
At the time that the data was censored, 12 (7.9%) children had been made aware of their own HIV+ status: 0% of children < 3 years of age (n = 0), 2.4% of children 3–5 years (n = 1), 7.5% of children 6–8 years (n = 3), 25% of children 9–11 years (n = 3) and 83% of children 12–15 years (n = 5). Children who had not been disclosed to were given partial, inaccurate, or no information by caregivers.