A prospective study of the association of serum neopterin, beta 2-microglobulin, and hepatitis B surface antigenemia with death in infants and children with HIV-1 disease.

A high percentage of HIV-1-infected infants and children in Romania are coinfected with hepatitis B virus. Little information is available on the impact of concurrent hepatitis B infection on the course of HIV-1 infection. We conducted a prospective cohort study over 1 year in a group of 68 HIV-1-infected infants and children to determine whether hepatitis B surface antigenemia, neopterin, and beta 2-microglobulin (B2M) predicted death. Among the 44 hepatitis B surface antigen-positive (HBsAg+) subjects at enrollment, 13 (30%) died during 1 year of follow-up. In comparison, two of 24 (8%) HBsAg-negative subjects died (RR = 7.7; p = 0.05). Higher initial serum concentrations of neopterin and B2M were negatively associated with survival. After stratifying by baseline clinical evidence of HIV-related disease, survival was negatively associated with HBsAg+ status (p = 0.04) in 33 children in stage P-2, adjusting for age, serum neopterin, and serum B2M levels. The results of this study suggest that serum neopterin is a marker for severity of clinical illness and that HBsAg+ status increases the mortality rate among children with clinical evidence of HIV infection.

Association between neopterin and beta-2-microglobulin levels and HIV status in Romanian orphanage children.

Serologic markers of immune activation, neopterin and beta-2-microglobulin (B2M), have been shown to predict progressive human immunodeficiency virus type 1 (HIV-1) disease based on cohort studies in adults. Both parameters appear also to be valuable in distinguishing HIV-1 infants with progressive disease from asymptomatic infants and HIV-1 seronegative infants. In a cross-sectional study we examined the utility of neopterin and B2M testing in 135 infants of an orphanage in Romania, 69 of the infants (51%) were found to be HIV-1 antibody seropositive; 95% of the 135 infants were either hepatitis B virus (HBV) antigen or antibody seropositive. In the HIV-1 seronegative infants B2M was higher in those with HBV antigenaemia. Serum neopterin and B2M concentrations were higher in HIV-1 seropositive than in seronegative infants (p = 7 x 10(-12) and 1 x 10(-6)). Children with CDC stage P2 had only slightly higher neopterin and B2M values as compared to stage P1 (P = 0.04 and 0.08). Our study indicates that measurement of neopterin and B2M is useful to monitor HIV-1 infection, particularly in areas where laboratory facilities are limited. Both parameters continue to be associated with HIV-1 infection even when there is a high background rate of other infections.