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Background:  Few data concerning clinical and laboratory consequences and safety of unplanned treatment interruptions in perinatally HIV-infected children previously on long-term therapy are available.

Methods:  We performed a retrospective chart review of perinatally HIV-infected children at our clinic to address this question. Record review included age, sex, and ethnicity of patient; duration of treatment interruption; CD4 count and plasma RNA prior to interruption and just before re-starting therapy; CD4 nadir at any time prior to interruption; incidence of opportunistic infections during the interruption; and incidence of immune reconstitution syndromes. Data were analyzed using means and ranges. Patients were required to have been off therapy for at least 3 months. Use of opportunistic infection prophylaxis was noted.

Results:  Of 76 perinatally HIV-infected patients on ART, 16 (21%) had 19 unplanned treatment interruptions that lasted 3 months or longer (mean 12.4 months, range 3 to 43 mo). Mean age at interruption was 14.8 years (4 to 23 years), 53% were female, 53% were Hispanic, and 47% were African American. Mean CD4 count and plasma RNA at treatment interruption were 459 cells/mm³ (21%) and 61,942 copies/ml, respectively (CD4 23 to 1428, 7 to 47%; RNA < 50 to 244,465 copies/mL). Mean CD4 count and plasma RNA at re-initiation of therapy were 193 cells/mm³ (12%) and 144,200 copies/mL, respectively (CD4 24 to 308, 4 to 25%; RNA < 400 to > 750,000 copies/mL). The average CD4 decline was 21 cells/month and 257 cells/year. No opportunistic infections were documented during the interruptions, however 63% were taking opportunistic infection prophylaxis. By 4 to 8 weeks after re-starting therapy, 16 patients had an average CD4 count of 302 cells/mm³ (27 to 707) 14.6% and a plasma RNA of 9366 copies/mL (< 50 to 99,510). At 6 months, CD4 count improved to 332 cells/mm³ (174 to 868) 16.4% and plasma RNA was 5356 copies/mL (< 50 to 60,242). No instances of immune reconstitution syndrome were noted. Three patients (19%) remain off therapy with stable CD4 counts.

Conclusions:  Our results indicate that perinatally infected children/adolescents who interrupted therapy experienced significant decreases in CD4 count/percentage, increases in plasma RNA, but no opportunistic infections. After re-initiation of therapy, CD4 counts have improved at 6 months but not to pre-interruption baseline. Plasma RNA has improved significantly. These data raise concerns about the safety of stopping therapy in perinatally HIV-infected children. Further study is warranted.

Keywords: treatment interruption; CD4 count; opportunistic infection