MICROBIOLOGY

  • Human T-cell leukemia virus I and II (HTLV I and II): members of human type C retroviruses.
  • Dx by HTLV-I or HTLV-II ELISA; greater sensitivity than Western blot and PCR.

CLINICAL

  • Most infections asymptomatic in general population. Not known if HIV+ pts more likely to develop disease.
  • HTLV-I
    • Endemic in Caribbean, southern Japan, parts of Africa, South America. Transmitted by breast feeding, contaminated blood products, IDU, sexual contact.
    • Adult T cell leukemia (ATL): 5% lifetime risk. Presents with B Sx, lymphadenopathy. Skin involvement (plaques, nodules) common.
    • HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP): 0.5-2.0% lifetime risk. Progressive disease with leg stiffness, weakness, low back pain, bladder dysfunction.
    • HTLV-I/HIV coinfected pts have higher CD4 counts than HTLV-I-negative HIV+ pts. OIs occur at higher CD4 counts than seen in HTLV-I-negative pts.
    • Can cause immunosuppression; associated with Strongyloides hyperinfection and decreased reactivity to PPD.
    • Vast majority of infected individuals will not develop disease.
  • HTLV-II
    • Endemic among IDUs; seroprevalence approximately 20%.
    • Not definitively shown to cause human disease, but some reports suggest that it can cause HAM/TSP-like syndrome.
  • Effect of HTLV-I/II on HIV disease progression controversial, with different studies reaching opposite conclusions.

SITES OF INFECTION

  • CD4 cells are main target of infection of HTLV-I.
  • HTLV-I-infected CD4 cells found in CSF of pts with HAM/TSP.
  • In ATL, circulation of monoclonal transformed cells bearing HTLV-I provirus.
  • HTLV-II infects peripheral blood mononuclear cells.

TREATMENT

Asymptomatic Infection

  • No evidence for benefit of antiviral therapy. HTLV genome integrated into host DNA; therefore, eradication probably not possible.

ATL

  • Conventional chemotherapy (standard regimen of vincristine, cyclophosphamide, doxorubicin, prednisone ranimustine, vindesine etoposide, carboplatin)
  • Small prospective phase II trial showed encouraging results with AZT 1 gm/d PO and alpha interferon (9 MU/d SQ).
  • A humanized anti-CCR4 antibody (mogamulizumab) has been shown to be effective as monotherapy or in combination with chemotherapy

HAM/TSP

  • Corticosteroids, cyclophosphamides, alpha interferon, IVIG, plasmapheresis, and danazol have been used with inconsistent results.
  • NRTIs have been tried based on in vitro activity against HTLV-I. AZT (1-2 gm/d) or 3TC (150 mg twice-daily) alone or AZT (250 mg twice-daily) and 3TC (150 mg twice-daily) used in 3 small studies. While decreased proviral HTLV-I load seen, Sx did not improve in most pts. TDF recently shown to have good in vitro activityagainst HTLV-I. In recent small randomized study of HIV-negative pts, 6 mos of AZT (300 mg twice-daily) and 3TC (150 mg twice-daily) had no effect on HTLV proviral load or clinical Sx
  • If ART to be initiated in coinfected pts, include AZT, TDF, and/or 3TC in pts with HAM/TSP or ATL if possible.
  • If NRTIs to be started for coinfected pts with HAM/TSP, should be used as component of ART to prevent NRTI resistance.

Prevention

  • CDC recommends that pts with asymptomatic infection not breast feed, donate blood, or share needles. Latex condoms should be used.

Basis for recommendation

  1. Guidelines for counseling persons infected with human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II). Centers for Disease Control and Prevention and the U.S.P.H.S. Working Group. Ann Intern Med. 1993;118(6):448-54.  [PMID:8382459]

    Comment: A practical set of guidelines from the CDC.

References

  1. Bangham CRM. Human T Cell Leukemia Virus Type 1: Persistence and Pathogenesis. Annu Rev Immunol. 2018;36:43-71.  [PMID:29144838]

    Comment: A comprehensive review of HTLV-I

  2. Sato T, Coler-Reilly ALG, Yagishita N, et al. Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy. N Engl J Med. 2018;378(6):529-538.  [PMID:29414279]

    Comment: Phase1-2a trial showed improved mobility and muscle tone and a a decrease in HTLV-1 proviral load and inflammatory markers in patients with steroid-refractory HAM
    Rating: Important

  3. Ishida T, Jo T, Takemoto S, et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015;169(5):672-82.  [PMID:25733162]

    Comment: The complete response rate in patients treated with combination therapy was higher (52%) than patients treated with mogamulizumab monotherapy (33%).

  4. Ogura M, Ishida T, Hatake K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32(11):1157-63.  [PMID:24616310]

    Comment: An objective response was seen in 35% of patients with relapsed disease who were treated with mogamulizumab.

  5. Croda MG, de Oliveira AC, Vergara MP, et al. Corticosteroid therapy in TSP/HAM patients: the results from a 10 years open cohort. J Neurol Sci. 2008;269(1-2):133-7.  [PMID:18258264]

    Comment: Open study of 39 patients with HAM/TSP treated with pulses of methylprednisolone (1 gm/d x 3 days) every 3-4 mos. After mean follow up of 2.2 yrs there was significant improvement of some Sx

  6. Kchour G, Makhoul NJ, Mahmoudi M, et al. Zidovudine and interferon-alpha treatment induces a high response rate and reduces HTLV-1 proviral load and VEGF plasma levels in patients with adult T-cell leukemia from North East Iran. Leuk Lymphoma. 2007;48(2):330-6.  [PMID:17325893]

    Comment: 9 pts with ATL treated with AZT (200-900 mg/d PO) and IFN alpha (3-5 million units daily SQ). 7 pts had either partial or complete response.

  7. Turci M, Pilotti E, Ronzi P, et al. Coinfection with HIV-1 and human T-Cell lymphotropic virus type II in intravenous drug users is associated with delayed progression to AIDS. J Acquir Immune Defic Syndr. 2006;41(1):100-6.  [PMID:16340481]

    Comment: More recent study showing protective effective of HTLV-II coinfection in HIV-1 positive IDUs. Interestingly, in 5 treated coinfected patients there was increase in HTLV-II proviral load, while HIV viral load dropped, suggesting that HAART does not treat HTLV-II.
    Rating: Important

  8. Beilke MA, Theall KP, O'Brien M, et al. Clinical outcomes and disease progression among patients coinfected with HIV and human T lymphotropic virus types 1 and 2. Clin Infect Dis. 2004;39(2):256-63.  [PMID:15307036]

    Comment: Study showed improved survival and decreased progression to AIDS in HTLV-II-coinfected patients. These pts more likely to have other clinical complications, however. Trend towards improved survival in HTLV-I-coinfected pts. While higher CD4 counts seen in coinfected pts, no difference in frequency of OIs.

  9. Araujo A, Hall WW. Human T-lymphotropic virus type II and neurological disease. Ann Neurol. 2004;56(1):10-9.  [PMID:15236397]

    Comment: Critical review of literature linking HTLV-II to neurological disease.

  10. Macchi B, Balestrieri E, Mastino A. Effects of nucleoside-based antiretroviral chemotherapy on human T cell leukaemia/lymphotropic virus type 1 (HTLV-1) infection in vitro. J Antimicrob Chemother. 2003;51(6):1327-30.  [PMID:12716774]

    Comment: Looks at the effects of NRTIs on HTLV-I replication in vitro.

  11. Scapellato PG, Bottaro E, Brieschke MT, et al. CD4 cell count among HIV-infected patients with an AIDS-defining disease: higher count in patients coinfected than in those not coinfected with human T-cell lymphotropic virus type I. J Acquir Immune Defic Syndr. 2003;33(2):279-80.  [PMID:12794568]

    Comment: Retrospective study found CD4 count of 160 in 6 treatment-naive HTLV-I/HIV coinfected pts vs. 62 in 42 HTLV-negative, HIV+ pts who presented with AIDS defining disease.

  12. Thorstensson R, Albert J, Andersson S. Strategies for diagnosis of HTLV-I and -II. Transfusion. 2002;42(6):780-91.  [PMID:12147033]

    Comment: Detailed study of methods used in the diagnosis of HTLV infection.

  13. Hermine O, Allard I, Lévy V, et al. A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma. Hematol J. 2002;3(6):276-82.  [PMID:12522449]

    Comment: 19 pts with ATL, 6 of whom had been treated with chemotherapy, received AZT 1 gm/d and alpha interferon 9 MU SQ once-daily for >2 mos. Of 17 who could be evaluated, 9 had complete response, 4 had partial response. 15 relapsed after a median of 7 mos.

  14. Brites C, Alencar R, Gusmão R, et al. Co-infection with HTLV-1 is associated with a shorter survival time for HIV-1-infected patients in Bahia, Brazil. AIDS. 2001;15(15):2053-5.  [PMID:11600839]

    Comment: This study from Brazil, where HTLV-I is endemic, showed shorter survival in HTLV-I/HIV-coinfected pts than in HTLV-I seronegative HIV-infected pts.
    Rating: Important

  15. Eskild A, Samdal HH, Heger B. Co-infection with HIV-1/HTLV-II and the risk of progression to AIDS and death. The Oslo HIV Cohort Study Group. APMIS. 1996;104(9):666-72.  [PMID:8972691]

    Comment: Relative risk of progression to AIDS was 2.1 in a cohort of 30 HTLV-II/HIV-coinfected pts when compared to HTLV-II seronegative HIV positive pts.

  16. Hershow RC, Galai N, Fukuda K, et al. An international collaborative study of the effects of coinfection with human T-lymphotropic virus type II on human immunodeficiency virus type 1 disease progression in injection drug users. J Infect Dis. 1996;174(2):309-17.  [PMID:8699060]

    Comment: Study compared 61 HTLV-II/HIV-I coinfected pts to 309 HTLV-II seronegative HIV+ pts. No difference in rate of CD4 count decline or progression to AIDS in the 2 cohorts.

  17. Gill PS, Harrington W, Kaplan MH, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995;332(26):1744-8.  [PMID:7760890]

    Comment: 19 pts with ATL, some of whom had failed chemotherapy, treated with AZT (1 gm/d) and alpha-interferon (5-10 MU SQ once-daily). 26% complete response and 32% partial response.

  18. Briggs NC, Battjes RJ, Cantor KP, et al. Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users. J Infect Dis. 1995;172(1):51-8.  [PMID:7797946]

    Comment: 98% of all HTLV infections in U.S. IDUs attributable to HTLV-II. Seroprevalence higher in HIV-infected pts.

HTLV-I/IIis the Johns Hopkins Guides Word of the day!

Last updated: December 30, 2019