Highlights of the HIV/AIDS research in St S. Nicolau Institute of Virology
After the fall of the communist regime in 1989 the St. S. Nicolau Institute of Virology reported the first iatrogenic AIDS outbreak in children (I.V. Patrascu and S. N. Constantinescu, Lancet 1990, 667, 335). By December 1990, 1168 AIDS cases were reported, of which 99.3% were in infants and children less than 4 years of age, and 683 (62.4%) in abandoned children living in public institutions at the time of diagnosis. Blood, blood products, and reusable unsterilized needles and syringes were probably the main route by which HIV spread in the infant population in medical institutions. These findings had a major with a major impact on HIV testing in Romania and on pediatric AIDS pathogenesis worldwide. The second wave of paediatric AIDS epidemic in Romania eas reported between 1994-95, in children living with their families, where both parents were HIV negatives. Presently, Romania has reported a cumulative total of 17 396 cases of HIV/AIDS: 5 580 cases of HIV infection; 8 247 AIDS cases, 3 569 AIDS deaths. (Source: UNAIDS/WHO epidemiological fact sheets on HIV/AIDS and STD, 2004 update)- the majority of these cases being horizontally acquired before 1990, through unsafe parenteral treatments. Nowadays. 7904 patients are evaluated in The Regional AIDS Centers and 4983 (63%) are receiving antiretroviral treatment (2287 children and 2696 adults-mean age: 13-18 years (Source: Romanian AIDS Commission, 2005).
The antigenic diversity of circulating strains. Early studies conducted in IVN (Cernescu CE et al J. Infect Dis. 1994, 170(4): 1043-4) on institutionalized children infected through contaminated blood-derived products and unsterilised needles and syringes have reported the prevalence of a single particular HIV1 subtype, called subtype F, a minor form, found only in Brazil and in Central Africa-a finding still under intense study. The analysis of the relative incidence of different HIV-1 subtypes over a 6 years period revealed relatively stable profiles of diversity and the constant predominance of subtype F among the adults from Bucharest. Genotyping by heteroduplex mobility assay or by sequence analysis of the C2-V3 envelope region support the steady predominance of subtype F both among children and adults from regions all over the country. In an undergoing study initiated in our laboratory, 75% of the samples collected after 2001 from patients heavily treated with antiretrovirals were assigned by sequencing to the genotype F1. All the results imply that the subtype F1, derived from African subtype D, is the major player in the Romanian HIV epidemic, suggesting its founder effect, whereby the earliest genetic form successfully introduced into a population establishes itself as predominant, gaining an initial advantage over other genetic forms arriving later.
Pediatric AIDS encephalopathy. One of the most salient features of the pediatric HIV infection is the early involvement of the central nervous system. The affected children present a large panel of neurologic signs characterized by a loss of developmental milestones, involving both motor and cognitive functions, termed pediatric HIV-1 encephalopathy. A prospective study was conducted in the IVN by correlating neurological exanimation, psychological and developmental analysis with virological and immunochemical investigations in the CSF and sera of children with AIDS, but without other common opportunistic infections or malignancies of the central nervous system. A late and discrete involvement of the blood-brain barrier with a secretor or transsudativ-secretar profile of the proteinorachia was observed in the evolution of pediatric AIDS encephalopathy, while intrathecal synthesis of specific anti HIV antibodies was recorded in all subjects, irrespective of their neurological status. A distinct pattern of WB profiles in sera and CSF was recorded in the evolution of AIDS encephalopathy in children The decline in anti gag antibody reactivity was found to be an earlier indicator of disease progression than p24 antigen concentration in CSF. Using a panel of V3 loop synthetic peptides, reproducing consensus PND of different HIV geographic isolates we established the independent evolution of neurotropic strains.
Investigation of the natural history of HBV and HCV coinfections in HIV infected children. Undergoing studies in IVN revealed a substantial percentage of HIV-infected Romanian adolescents with evidence of past or present HBV infection (78.3% of HIV-infected adolescents vs. 31.7% of HIV-uninfected controls), despite the absence of clinical signs. The magnitude of HBV coinfection contrasts with the amplitude of intervention measures: reduction of risks factors for acquisition of blood-borne pathogens, hepatitis B vaccination, and antiretroviral therapy. Severely immunosuppressed patients may act as "supershedders" and maintain a high rate of HBV infection in the community. This is supported by the fact that HIV/HBV-coinfected patients manifest decreased responses to the HBV vaccine, their seroconversion rates to the recombinant 3-dose HBV vaccine being 20%, compared with 78.4% in the control group. Most evidence supports the idea that HIV accelerates the progression of HBV disease. Our studies suggest that in HIV-infected adolescents, the degree of immunosuppresion is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease. The incidence of HBV replicative markers is almost double in patients with immunological AIDS and a significantly decreased clearance rates for HBeAg was demonstrated in severely immunodepressed patients.