Antiviral effect of raltegravir on HTLV-1 carriers.
نویسندگان
چکیده
BACKGROUND In vitro studies support that integrase inhibitors, such as raltegravir, may inhibit human T cell lymphotropic virus type 1 (HTLV-1) replication. However, this hypothesis has not been tested in vivo. METHODS HTLV-1-infected individuals were invited to participate in a pilot, open study that examined whether 400 mg of raltegravir twice daily could exhibit any recognizable virological effect over 12 months. Proviral DNA was measured by a real-time PCR targeting the pol region. HTLV-1 integrase sequences were obtained from peripheral blood mononuclear cells (PBMCs) at baseline and during follow-up. RESULTS A total of five HTLV-1-infected individuals entered the study. All were infected with HTLV-1 subtype a. Two patients had HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the rest being asymptomatic. The HTLV-1 proviral load was high in all cases (median 758 HTLV-1 DNA copies/10(4) PBMCs). Following the initiation of raltegravir therapy and for up to 6 months, both of the HAM/TSP patients experienced a transient decline in the HTLV-1 proviral load (2248 to 519 and 1033 to 861 copies/10(4) PBMCs, respectively), returning to baseline levels on subsequent determinations. No significant changes in the HTLV-1 proviral load were noticed in the three asymptomatic individuals (median proviral load of 755 copies/10(4) PBMCs over time). A total of 20 integrase sequences could be obtained from the five patients, and no genotypic substitutions were recognized comparing baseline and follow-up specimens under raltegravir. CONCLUSIONS Treatment with raltegravir in HTLV-1-infected individuals does not result in a significant reduction of proviral load beyond 6 months of therapy. The lack of continuous viral replication cycles in chronic HTLV-1 carriers most likely explains our findings.
منابع مشابه
How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy
Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL), or a neurological disorder n...
متن کاملHLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy.
The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease ...
متن کاملThe Impact of Immune Response on HTLV-I in HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Human T lymphotropic virus type I (HTLV-I) is a retrovirus which is associated with adult T cells leukaemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of HTLV-I-infected individuals. It is not clear why a minority of HTLV-I-infected individuals develop HAM/TSP and majority remains lifelong carriers. It seems that the interaction between the v...
متن کاملPatterns of serum type 1 and type 2 immune markers in healthy carriers of HTLV-I.
Type 1 immunity appears to be diminished in healthy Japanese carriers of human T-lymphotropic virus type I (HTLV-I), but type 2 status remains undetermined. To further examine the subclinical effect of HTLV-I on host immunity, we measured serum antibodies to the Epstein-Barr virus (EBV) in 415 healthy Japanese adults to broadly characterize type 1 status. Levels of the type 2 biomarkers total i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of antimicrobial chemotherapy
دوره 67 1 شماره
صفحات -
تاریخ انتشار 2012