Effects of Microbial Co-infections on HIV-infected Individuals and Intervention with Lactoferrin

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1. Effects of GB virus-C (GBV-C) infection on HIV-infected individualsi) Field studies in Northern Thai Lampang HIV CohortApproximately 11% of HIV-infected individuals in the Cohort had GBV-C viremia. Genotypic analyses demonstrated that 27%, 51% and 22% were genotype-2 (G2), G3 and G4, respectively. With statistical significance, HIV (+)/GBV-C(+) patients had higher CD4-positive T cell counts, lower HIV loads, AIDS-defining illnesses in lower incidence, and better survival rate than HIV(+)/GBV-C(-) patients. Anti-HIV effect was most powerful in G2, followed by G4, while G3 had little effect.ii)Bench studiesA series of infectious molecular GBV-C clones were constructed : they have Env gene derived from G2, G3 or G4 in the backbone of G2 genome. Peripheral blood mononuclear cells were transfected with those molecular clones or parent plasmid, and infected with HIV-1 in vitro. It was demonstrated that all those molecular clones variably suppressed HIV infection in this assay.2. Studies on other virusesi) TT virus (TTV)Epidemiological surveys in healthy Japanese children and adults revealed that TTV infection rates were 6%, 34%, 90% and 84% among one-month-old infants, four-month-old infants, 42-month-old toddlers and adults, respectively. G3 is the most common genogroups throughout all age groups. G1 is the second most common at and beyond 42 months, while G4 is the second most common at or before 4 months. TTV infection rates were higher in febrile infants than healthy infants, suggesting its role in infantile febrile illnesses, including aseptic meningitis. ii)Human herpesvirus-8 (HHV-8)Approximately 5% of HIV-infected individuals in the Cohort were also infected with HHV-8.3. Antiviral effects of lactoferrinDaily intake of lactoferrin (100 mg daily) significantly ameliorated rotaviral gastroenteritis in otherwise healthy Japanese children.