Of 451 HIV-infected children enrolled in AMP, 444 completed the baseline visit and had received ART continuously for at least six months as of May 1, 2010. Of these 444 children, 101 (23%) had at least one ≥3 month TI. There were 12 (2.7%) children who had two TIs. First TIs occurred prior to enrollment in AMP for 90 (89%) of the 101 children with a documented TI. Children with TI were born significantly earlier than those who never interrupted therapy (, p<0.0001). Children with TI were similar to those without TI in terms of sex (40% vs. 48% males, p=0.14), race (71% vs. 72% Black, p=0.14), ethnicity (26% vs. 24% Latino, p=0.24), age at ART initiation (1.0 vs. 0.8 years, p=0.6), CDC class at entry to AMP (26% vs. 23% class C, p=0.92). Of the 101 interrupters, the 81 who had CD4 results available at the time of TI and at least one additional time point during the interruption were included in subsequent analyses.
Comparison of population with antiretroviral treatment interruption (TI) (N=101) to population that initiated but never interrupted antiretroviral treatment (N=343)
The majority of the 81 children who interrupted ART were female and Black (). At the time of TI, 55% were at least 10 years old, 62% had been on a HAART regimen, and the median duration of their most recent ART regimen was 36.6 months. ART was initiated at a median age of 1.0 year (interquartile range 0.4-2.3 years). At TI, the median CD4% (32%) and CD4 count (709 cells/mm3) reflected generally good immunologic status; 3.7% (3/81) had a CD4% <15% at TI. The median log HIV VL at TI was 3.1, but only 24% had VL ≤400 copies/mL. CDC clinical category C conditions occurred in 28% of children at some time before TI. The nadir CD4% of 21.0% occurred at a median age of 3.8 years (Q1-Q3, 1.7, 7.3), while the nadir CD4 count of 470 cells/mm3 occurred at a median age of 6.8 years (Q1-Q3, 3.8-10.1). Most children had experienced a rise in CD4% (median increase of 10%) and in CD4 count (median increase of 194 cells/mm3) between their historical CD4 nadir and the time of TI.
Demographic and clinical characteristics of the 81 perinatally HIV-infected children with antiretroviral therapy interruption (TI) and available CD4 information.
During TI, the CD4 percent dropped a mean of -0.66% and median (IQR) of -0.51% (-0.92% to -0.13%) per month, and the CD4 count dropped a mean of -20 and median (IQR) of -12.7 (-29.7 to -4.8) cells/mm3 per month. However, there was a wide range of CD4 slopes among the interrupters, ranging from children with extreme rates of decline in CD4% (-3.54% per month) and CD4 count ( -148 cells/mm3 per month) to those who had actual increases (positive slope) in CD4 values after interruption, as high as +1.34% and +31.3 cells/mm3 per month. The median (Q1, Q3) duration of TI was 16.2 (6.5, 24.4) months. Most (79%) subjects reinitiated ART; the reasons for re-initiating ART were not available, but there were no AIDS-defining illnesses or deaths during TI. The median (range) duration of follow-up from the time of TI was 4.5 years (0.3, 14.2).
Of all of the demographic and clinical characteristics evaluated (), the only factors potentially associated (p<0.2) with more rapid rate of decline in CD4% were female sex (-0.76% vs. -0.51% per month, p=0.09), higher CD4% at interruption (-0.02% per month for each 1% higher CD4% at TI, p=0.05), CDC clinical category C (-0.89% vs. -0.58%, p=0.16), and higher peak VL before interruption (-0.15% per one log increase in VL, p=0.06) (). The strength of these associations was unchanged in multivariable analysis.
Univariable and multivariable predictors of CD4% slope (change in CD4% per month) during antiretroviral therapy interruption (TI).*
When children were divided into the quartile with the fastest rate of CD4% decline (lowest quartile, ΔCD4% ≤ - 0.92% per month) and the quartile with the most stable CD4% (highest quartile, ΔCD4% ≥ -0.13% per month), the children in the lowest quartile were significantly more likely than those in the highest quartile to have a history of CDC category C disease (45% vs. 10%, p=0.03) (). There was a non-significant trend for those in the lowest quartile to have had a greater increase in CD4% from nadir until interruption, to have a higher peak VL before interruption, and to have been on a greater number of ART regimens prior to interruption.
Characteristics associated with extreme quartiles of CD4% slope during treatment interruption (TI).