Genetic Analysis of the Full-Length gag Gene from the Earliest Korean Subclade B of HIV-1: An Outbreak among Korean Hemophiliacs.

We determined the earliest full-length HIV-1 gag gene sequences in 110 patients with HIV-1, including 20 hemophiliacs (HPs) and 90 local controls (LCs). The gag gene from stored sera was amplified using RT-PCR, and was subjected to direct sequencing. Phylogenetic analysis indicated that 94 and 16 sequences belonged to the Korean subclade of HIV-1 subtype B (KSB) and subtype B, respectively. A total of 12 signature pattern amino acids were found within the KSB, distinct from the worldwide consensus of subtype B. Within the KSB, the gag gene sequences from donors O and P and those from the 20 HPs comprised two subclusters. In particular, sequences from donor O strongly clustered with those of eight HPs. Moreover, signature pattern analysis indicated that 14 signature nucleotides were shared between the HPs and LCs within KSB (p < 0.01). Among the 14 nucleotides, positions 9 and 5 belonged to clusters O and P, respectively. In conclusion, signature pattern analysis for the gag gene revealed 12 signature pattern residues within the KSB and also confirmed the previous conclusion that the 20 HPs were infected with viruses due to incompletely inactivated clotting factor IX. This study is the first genetic analysis of the HIV-1 gag gene in Korea.

Signature pattern analysis for the full-length env gene of the earliest Korean subclade B of HIV-1: outbreak among Korean hemophiliacs.

The epidemiological link in the hypervariable env gene between viruses infecting HIV-positive hemophiliacs (HPs) and plasma donors was not studied. We determined full-length env gene sequences in 20 HPs, 3 plasma donors whose plasma was used for domestic clotting factor (DCF) production, and 54 local controls (LCs). Env genes from viruses in frozen stored sera obtained 1-3 years after diagnosis and from samples collected several years after infection were amplified via RT-PCR and subjected to direct sequencing. Phylogenetic analysis indicated that all sequences were subtype B, including 133 sequences from 77 cases (20 HPs, 3 plasma donors, and 54 LCs) belonging to the Korean subclade B (KSB) and 6 sequences from 5 cases that did not belong to the KSB. Env gene sequences from donors O and P and those of the 20 HPs comprised 2 subclusters within the KSB, although phylogenetic analysis did not support significant bootstrap values. In contrast, signature pattern analysis indicated signature nucleotides at 43 positions between the HPs and LCs (P < 0.05). In particular, specific signature nucleotides at 4 positions were fully conserved in the HPs, but not in the LCs (P < 0.0001). Furthermore, there were 26 signature residues within the KSB and were distinct from the worldwide consensus for subtype B. In conclusion, signature pattern analysis for the hypervariable env gene revealed an epidemiological link that the 20 HPs in this study had been infected with viruses from the DCF used for treatment, consistent with our previous finding.

Do hemophiliacs have a higher risk for dental caries than the general population?

OBJECTIVE: The aim of this study was to examine if patients with hemophilia were at increased risk for dental decay as compared to the general population. MATERIALS AND METHODS: Census sampling was used in this case-control study to recruit cases (patients with hemophilia) and a control group individuals recruited randomly from the general population, which were matched with cases based on gender, age and place of residence. Clinical examinations included dental health and salivary assessments (flow rate, buffer capacity, caries-associated bacteria) and a structured questionnaire which inquired about socioeconomic status and dental health-related behaviors. RESULTS: In the deciduous dentition, the overall caries experience (dmf) differed statistically significantly (P=0.003) between the hemophiliacs (2.6±2.6) and their matched healthy controls (6.1±2.5). Bivariate analyses did not reveal significant differences between cases and controls regarding salivary functions, except that higher bacteriological counts were found in healthy controls in deciduous dentitions than in patients with hemophilia (P=0.019). Children without hemophilia were from higher socioeconomic status families than hemophiliacs (P=0.004), but such differences were not found for adults (P=0.090). When compared to healthy adults, adult hemophiliacs had more gum bleeding at rest (P<0.001) as well as during their tooth brushing (P=0.007) and they also consumed more soft drinks than controls (P=0.025). CONCLUSIONS: Better dental health was observed in children with hemophilia as compared to children without it. There were no differences in dental health between adult hemophiliacs and healthy controls from the general population. None of the linear multiple regression models confirmed hemophilia to be an additional caries risk when it was controlled for other caries determinants.

Viral Hepatitis and Change of Lymphocyte Subpopulation in Hemophiliacs in Chonnam KwangJu area / 대한수혈학회지

BACKGROUND: Hemophiliacs are known to have higher risk of exposure of hepatitis virus and immunosuppression. The aim of this study is to investigate the positive rate of viral markers for hepatitis and anti-HIV and the changes of lymphocyte subpopulations in Hemophiliacs in Chonnam GwangJu area. METHODS: One hundred four patients who had visited to the Hemophilic Clinic, Chonnam University Hospital from 1999 to 2001 were enrolled. They were checked for type A, B, C hepatitis viral markers, anti-HIV and lymphocyte subpopulations. The prevalence of hepatitis and lymphocyte subpopulation were compared according to severity and age of hemophiliacs. RESULTS: Anti-HAV IgM, anti-HAV IgG, HBsAg, anti-HBs, anti-HCV were positive in 40%(22/55), 65.5%(66/101), 42.3%(42/97) of cases tested. Positivity of anti-HCV showed trends of increase according to the severity of hemophiliacs (P11 years old) (P=0.003, P<0.001, respectively). Although all enrolled patients were negative for anti-HIV, absolute T and B cells counts were decreased in 71.6% and 14.9% of patients, respectively and inversion of CD4/CD8 ratio were found in 65.7%. But there were no statistical difference in not only decrease of T and B cells but also inversions of CD4/CD8 ratio according to age and severity. CONCLUSION: The number of hemophiliacs with previous history of hepatitis B virus infection and seropositivity of anti-HCV were increased according to the age and severity of hemophilia. Active vaccinations of hepatitis B may be required in hemophiliacs. The greater part of hemophiliacs showed decrease in T cell count and inverted CD4/CD8 ratio. The hemophiliacs need a cautiion for infection and follow up tests for immunologic function.

A Comprehensive Study of Immunological Abnormalities in Korean Hemophiliacs

To determine laboratory evidence suggesting immunological abnormalities in persons with hemophilia, we evaluated the immunological status of 75 Korean hemophiliacs, seronegative for human immunodeficiency virus (HIV) antibodies, who have been treated only with Korean factor VIII concentrates. From this study, it was shown that Korean hemophiliacs had decreased CD4 levels, increased CD8 levels, and decreased CD4:CD8 ratios. Diminished lymphocyte response to the mitogens, phytohemagglutinin and concanavalin A, and decreased natural killer cell activity were observed in the hemophiliacs. In addition, production of interleukin-II in the hemophiliacs was lower than in the healthy controls. The percentage of B lymphocytes was significantly reduced but the serum levels of immunoglobulin (Ig) G were elevated. However, the serum Ig A and Ig M levels were normal. This study demonstrated a high frequency of immunological abnormalities in HIV antibody negative Korean hemophiliacs treated only with domestic factor VIII concentrates.