BACKGROUND: Lower percentages of CD4(+) T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4(+) lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4(+) cell percentage are maintained and whether they lead to normal CD4(+) cell percentages in children with severe immunosuppression. METHODS: The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4(+) cell percentage, using marginal structural models to account for confounding by severity. RESULTS: Initiation of any type of HAART increased CD4(+) cell percentage by 2.34% (95% confidence interval, 1.35%-3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4(+) cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4(+) cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4(+) cell percentage after 5 years of HAART did not reach normal levels. CONCLUSIONS: Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4(+) cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy.
BACKGROUND: Lower percentages of CD4(+) T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4(+) lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4(+) cell percentage are maintained and whether they lead to normal CD4(+) cell percentages in children with severe immunosuppression. METHODS: The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4(+) cell percentage, using marginal structural models to account for confounding by severity. RESULTS: Initiation of any type of HAART increased CD4(+) cell percentage by 2.34% (95% confidence interval, 1.35%-3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4(+) cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4(+) cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4(+) cell percentage after 5 years of HAART did not reach normal levels. CONCLUSIONS: Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4(+) cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy.
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Authors: Paula Braitstein; Adrian Katshcke; Changyu Shen; Edwin Sang; Winstone Nyandiko; Vincent Ooko Ochieng; Rachel Vreeman; Constantin T Yiannoutsos; Kara Wools-Kaloustian; Samwel Ayaya Journal: Trop Med Int Health Date: 2010-05-14 Impact factor: 2.622
Authors: Kristjana H Ásbjörnsdóttir; James P Hughes; Dalton Wamalwa; Agnes Langat; Jennifer A Slyker; Hellen M Okinyi; Julie Overbaugh; Sarah Benki-Nugent; Kenneth Tapia; Elizabeth Maleche-Obimbo; Ali Rowhani-Rahbar; Grace John-Stewart Journal: AIDS Date: 2016-11-28 Impact factor: 4.177