Neonatal factors associated with HIV long term non-progressors in a cohort of vertically infected children in Rio de Janeiro, Brazil ("Peixe" Project)

Abstract

There are only scarce data on HIV progression in vertically infected children in developing countries. The aim of this study is to describe factors from neonatal period associated with long term non-progression (LTNP), in a Brazilian cohort. A cohort study, with data systematically collected from the "Peixe" Cohort (cohort study of children conducted at the main HIV Pediatric Center in Rio de Janeiro, from 1996 to 2005). The study included children who were vertically infected and started follow up at 5 years of age or younger. LTNP, defined as not reaching category C or severe immunosuppression before 5 years of age. Neonatal and demographic factors were studied. Variables with p-value<0.15 were included in a logistic regression model. 213 patients were included, of whom 42% (89/213) were classified as LTNP. Variables independently associated with LTNP were: baseline (at study entry) CD4+ cells (per %) (OR= 1.06, 95%CI=1.01-1.12); age of initiating follow-up, per month (OR= 1.03, 95%CI=1.01-1.06); ZDV use duriing newborn period (OR= 3.31, 95%CI=0.86-12.71); use of antiretroviral (ART) before classification C or severe immunosuppression (OR= 5.89, 95%CI=2.03-17.10). Adjusting for age at the beginning of follow-up, antiretroviral that was unsuccessfully used to prevent maternal-to-child transmission (ZDV use in neonatal period) was associated with better prognosis. ARTs initiation before category C or severe immunosuppression was also associated with LTNP. Key-Words: HIV, antiretroviral therapy, long term non-progressors, children, Brazil.It is estimated that 20-40% of HIV-1-infected children present with rapid disease progression and develop AIDS within the first years of life [1][2][3][4]. On the other hand, 60-80% of infected children manifest less severe symptoms and many survive through adolescence [3][4][5][6]. In developed countries, advanced maternal disease, high maternal viral load, and maternal and infant immune suppression were associated with rapid HIV progression in children [7]. In developing countries, where the majority of perinatal infections occur, there are only scarce data on HIV progression and risk factors. Meanwhile, in some developed countries, all HIV infected children are treated with highly active antiretroviral therapy (HAART) in early infancy. [8]. Brazilian guidelines [9] recommend that HIV infected infants should be treated only if they present any stage B or C symptoms and/or are in immune categories 2 or 3 (CDC) [10]. Although there is some evidence that infants benefit from treatment started in their first year of life, with early HIV replication control and preservation of the immune system [3,4,11], aspects associated with HAART adverse events, adherence and emergence to drug resistant virus must also be considered [5]. Another important issue is the possibility that almost 50% [1-4] of these infants would be long-term nonprogressors (LTNP), and would not benefit from HAART until five years of age or older. It is important to identify early life events that might be associated...

Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age

“…The reasons for the differences are unclear but could include greater variation in cell counts, compared with cell percentages, and the cross-sectional measurement, which can vary with time. Being male was significantly associated with LTNP in this study; this finding differs from other pediatric LTNP studies3, 31 and requires confirmation in larger studies with longer periods of observation. We did not associate levels of HIV RNA with LTNP, although HIV RNA levels generally associated with decreases in CD4+ T cells17.…”

“…There are few studies of pediatric LTNPs31, 32. The Women and Infant Transmission Study followed 137 HIV-positive children from birth and found 10 to be LTNPs, defined as children with >25% and >500 cells/mm 3 CD4+ T cells at 8 years of age.…”

Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

“…Long‐term nonprogressors (LTNPs) are defined as children with perinatally acquired HIV‐1 infection who are antiretroviral therapy (ART) naïve, maintain normal‐for‐age CD4 counts (≥ 500 cells/μL at age ≥ 7 years) and remain free of manifestations of disease progression. Several large paediatric LTNP cohorts similar to our cohort have been described in South Africa/Durban , Uganda , Thailand and Cambodia , France and seven other European countries , Brazil , Puerto Rico and the USA . In India, there are limited reports on paediatric LTNP cohorts and analysis of their immune biomarkers .…”

“…The prevalence of paediatric LTNPs was 5-10% in South Africa [9], 13.6% in US cohorts [32,33], and 24% in cohorts from France and seven other European countries [13]. Our LTNP cohort had a median viral load of 34 813 copies/mL (IQR 13 038-80 873 copies/mL), whereas the median viral loads were 26 000 copies/mL in South Africa [10], 367 854 copies/mL in Brazil [14] and 118 716 copies/mL in the USA [32]. Interestingly, we observed a significant decline in the viral load with age over a period of 18 years (P < 0.0001) ( Fig.…”

Metabolic and infectious pathologies in Brazilian medical literature: a review

“…Hofer et al 55 described factors from the neonatal period associated with long-term non-progression of HIV in a Brazilian cohort of vertically infected children; Mercon et al 56 examined a cross section of HIV-infected patients in Rio de Janeiro and found that risk-based assessment does not distinguish between recent and chronic HIV-1 infection.…”