Human T-Cell Lymphotropic Viruses (HTLV) Workup

Updated: Feb 07, 2023
  • Author: Joseph M Yabes, Jr, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Laboratory Studies

Multiple serologic methodologies are commercially available for the diagnosis of HTLV-1 and HTLV-2 infections. Included in the diagnostic armamentarium are enzyme-linked immunosorbent assays (ELISA), chemiluminescence assays, and particle agglutination assays.

Any positive result in the aforementioned diagnostic studies should be followed by confirmatory western blot, immunofluorescence assay (IFA), or polymerase chain reaction (PCR).

Only individuals with risk factors for HTLV infection should undergo testing.

HTLV ELISA yields very high false-positive rates in areas of low prevalence. [65] In patients in whom testing is deemed to be appropriate, recent test comparisons have found that those widely available perform with similar diagnostic accuracy. [66]

Positive ELISA results in combination with indeterminate western blot findings can be interpreted as follows:

  • Cross-reactivity with Plasmodium falciparum infection
  • HTLV-3 or HTLV-4 infection
  • Delayed seroconversion with low antibody titers
  • False-positive ELISA result

In this setting, western blot testing may be repeated, and, if possible, a different confirmatory laboratory test (ie, HTLV PCR testing) should be performed. In a US-based study including more than 400 patients with indeterminate western blot results, only 1.4% had positive PCR results for HTLV infection. [48]

PCR testing has additional uses. PCR or EIA with virus-specific synthetic peptides is necessary to distinguish between HTLV-1 and HTLV-2. PCR is also required in infants whose results may be false-positive because of circulating maternal anti-HTLV antibodies. PCR also quantifies the proviral load, which is frequently used as a marker for progression, especially in HAM/TSP. It is expressed as “the number of HTLV-1 DNA copies per fixed number of peripheral blood mononuclear cells.” [49]

Patients diagnosed with HTLV-1 or HTLV-2 infection should also undergo the following tests:

  • Complete blood count with differential and peripheral blood smear
  • Complete chemistry with calcium level
  • Liver function tests
  • Lactate dehydrogenase testing
  • HIV screening
  • Viral hepatitis serology (A, B, C)
  • Rapid plasma reagin (RPR)
  • Purified protein derivative (PPD)
  • Strongyloides stercoralis serology and stool examination for ova and parasites (if the appropriate risk factors exist)

Imaging Studies

No specific imaging studies are recommended for asymptomatic HTLV infections. However, imaging studies may be considered in aiding in diagnoses/evaluation of HAM/TSP or ATL.


Brain MRI reveals nonspecific periventricular and subcortical white matter lesions in 50%-80% of patients with HAM/TSP; however, these lesions also occur in patients with asymptomatic HTLV-1 infections, and comparisons with controls have not been adequate. [49]


Chest radiography is important, particularly in patients with ATL, to assess for pulmonary complications, opportunistic infections, and lytic bone lesions.

CT scanning of the neck, thorax, abdomen, and pelvis is crucial in assessing for nodal involvement. [50] It can also aid in further assessment for opportunistic infections (ie, abscess formation, pneumonia, intestinal infections).



No specific procedures are recommended for asymptomatic HTLV infections.

Lumbar puncture to evaluate CSF for anti–HTLV-1 antibodies (and/or HTLV-1 proviral load) might be beneficial in establishing a diagnosis of HAM/TSP. The laboratory results often show a mild lymphocyte pleocytosis and increased protein levels. A proviral load ratio of CSF to peripheral blood that exceeds 1 supports a diagnosis of HAM/TSP. [49]

Lymph node biopsy may aid in the diagnosis of ATL.


Histologic Findings

No characteristic histologic findings are associated with asymptomatic HTLV infections.

HAM/TSP histopathology of the spinal cord shows perivascular and parenchymal infiltration of T cells, which worsens with the development of atrophy during disease progression. [49]

Peripheral blood smear is required for definitive diagnosis and categorization of ATL. ATL peripheral blood lymphocytes are found to have convoluted nuclei (cloverleaf or flower lymphocytes); provirus can be detected within these malignant cells.