and E. M. -O. to <250 copies/ml following 6 months of ART (32% infants vs . 73% children p <0. 0001). CD4% was higher at baseline in infants than children (19% vs . 7. 3%, p <0. 001). Older children had more rapid CD4% reconstitution than infants, but failed to catch up to infant CD4%, == Conclusion == Despite substantially higher CD4% at ART initiation, viral suppression was significantly slower among infants than older children. New strategies are needed to optimize infant outcomes on Alvimopan monohydrate ART. Keywords: HIV-infected infants, HIV-infected children, Pediatric HIV, Antiretroviral therapy, HIV viral load suppression, CD4 reconstitution == BACKGROUND == Infant HIV-1 viral loads are substantially greater than adult levels[1, 2], and as many as 50% of untreated HIV-1 infected African infants die by two years of age[3]. In contrast to acutely infected adults, vertically infected infants are sluggish to suppress virus[4] and many do not attain a discernable viral weight set-point[2]. Older untreated HIV-1 infected children, the vast majority of whom represent vertically infected survivors, have lower viral loads than infants[5], either due to lower viral setpoint achieved post-infancy or to high early mortality[6] in infants, which results in culling of unfavorable viral or sponsor characteristics among survivors. Response to antiretroviral therapy (ART) may also differ between infants, children, and adults. In adults, ART typically results in up to 95% achieving viral suppression within 6 months of ART initiation, varying Alvimopan monohydrate by regimen, the population under study and the definition of suppression used[79]. Similar rates of viral suppression have been shown in pediatric populations that include older children[9, 10]. However , infants have slower viral suppression[11, 12] and higher incidence of virologic failure[13]. While failure of ART viral suppression in infants may be due to higher baseline viral loads or challenges with ART faithfulness or dosing[14], it is also possible that aspects of the immune response that cause poor viral control in untreated infants may contribute to slower viral decline with ART. Immune recovery on ART usually occurs in tandem with viral decline[15, 16]. In contrast to poor viral suppression with ART, infants generally have better immune status on ART than older children[1719]; this may be due to their high thymic output[20] and higher age-specific CD4 counts and CD4%[2123], or to greater damage to the CD4 T-cell population among older children who have lived with untreated HIV for an extended period[2425]. As ART response is primarily assessed using CD4 monitoring in developing country settings[2629], treatment failure among infants in particular may be masked by their comparatively good CD4 counts and percentages[26, 29, 30]. Although drastically improved survival is achievable if ART is initiated early in infancy[31], in practice, infant diagnosis is often delayed[32] and early mortality on ART remains high[33]. In order Alvimopan monohydrate to understand whether impaired virologic and immunologic response to ART could explain high mortality post-ART in this population, we compared virologic and immunologic responses between infants starting ART in the Rabbit Polyclonal to OPRD1 first year of life versus children starting ART between the ages of 18 months to 12 years and conducted sensitivity analyses to address the potential contribution of chronic non-adherence to any differences found. Our hypothesis was that infants would have slower rates of viral suppression but comparable immune reconstitution to older children. == METHODS == == Cohorts == Data from two pediatric ART studies conducted in Nairobi, Kenya were used for these analyses. Both studies were approved by the University of Washington Institutional Review Board and the Kenyatta National Hospital Ethics and Research Committee. Each study has extended follow-up up to > 5 years; the current study utilized data on immunologic and virologic markers obtained during the first 2 years of ART. Recruitment and enrollment procedures have been described in detail.