HIV and HTLV-1 Coinfection: The Need to Initiate Antiretroviral Therapy

According to the latest Department of Health and Human Services guidelines for the use of antiretroviral therapy (ART) in HIV-1-infected persons, initiation of ART is recommended for all HIV-infected persons regardless of the CD4 count. In resource-limited settings where ART is not available for all patients, treatment should be prioritized for those with the following conditions: pregnancy, CD4 count <200 cells/mm or AIDS-defining illness, HIV-associated nephropathy, HIVassociated dementia, hepatitis B virus coinfection, and acute HIV infection. We suggest that coinfection with human T-cell lymphotropic virus type 1 (HTLV-1) should be added to this prioritized list for the following reasons: The predictive value of CD4 count as a marker of HIV-related immunosuppression and disease stage for persons coinfected with HIV and HTLV-1 is likely not the same as for persons infected with HIV alone. Human T-cell lymphotropic virus type 1 promotes the clonal expansion of CD4-infected T lymphocytes, causing an artificially elevated CD4 count in coinfected persons. Compared to HIV-infected patients with CD4 counts greater than 200 cells/mm, HIV/HTLV-1coinfected individuals with similar CD4 counts are at increased risk for developing opportunistic infections. Thus, a high CD4 count in coinfected persons does not necessarily reflect a competent immune system. HIV/HTLV-1 coinfection is associated with accelerated progression to AIDS and worse outcomes of HIV-related opportunistic infections. Human T-cell lymphotropic virus type 1 induces HIV viral replication and the transition from Mto T-tropic HIV phenotype, which is often a marker of HIV disease progression. In addition, compared to individuals infected with only HIV, HIV/HTLV-1-coinfected individuals have higher production of proinflammatory cytokines, most notably interleukin 2 and interferon-g, suggesting that metabolic and cardiovascular complications mediated by chronic immune activation could be more pronounced among coinfected individuals. In countries with a high burden of tuberculosis, tuberculosis is more common in persons infected with both HIV and HTLV-1. The risk of tuberculosis is about 2.5-fold higher in HIV/HTLV-1-coinfected patients compared to patients with HIV infection alone, and both morbidity and mortality are higher in patients with HIV/HTLV-1 coinfection. Using quantitative HTLV-1 proviral load (PVL) as an indicator of when to initiate ART in asymptomatic HIV/HTLV-1coinfected individuals with preserved CD4 counts is often impractical due to limited laboratory capacity in countries where HTLV-1 infection is endemic. In addition, HTLV-1 PVL varies widely in asymptomatic carriers and in persons with HTLV-associated disease; and the relationship between HTLV-1 PVL and HIV-associated manifestations in HIV/ HTLV-1-coinfection has not been well established. Hence, neither quantitative HTLV-1 PVL nor CD4 count is a clinically useful indicator of disease or immune status in the setting of HIV/HTLV-1 coinfection. In contrast, limited evidence suggests that coinfection with HTLV-2, common among HIV-infected injection drug users in the United States and Europe, has a protective effect against progression of HIV infection to AIDS. Human T-cell lymphotropic virus type 2 has been associated with increased CCL3L1 expression, a chemokine that inhibits HIV-1 cell entry by binding to CCR5. Furthermore, HIV/HTLV-2-coinfection has been linked to a ‘‘long-term nonprogressor’’ phenotype. Therefore, the effect of HTLV-1 and HTLV-2 coinfection upon HIV infection may be different, and our recommendation for considering earlier initiation of ART in persons with HIV/ HTLV-1 coinfection may not apply to people with HIV/ HTLV-2 coinfection.