Short Communication: Failures in Detecting HTLV-1 and HTLV-2 in Patients Infected with HIV-1

Abstract

Changes in retrovirus acquisition/transmission behaviors have been reported in Brazil, with a concerning increase in HIV-1-infected individuals aged 15-39 years. In São Paulo, HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections have been associated with intravenous drug use and failure to detect HTLV-1/2 (human T cell lymphotropic virus types 1 and 2) with immunosuppression and the use of highly active antiretroviral therapy (HAART). Negative results for HTLV serologic [western blotting (WB)] and molecular [real-time PCR pol (qPCR)] confirmatory assays have been reported, whereas the best sensitivity has been found for INNO-LIA (LIA). In this study, we expand our previous data by analyzing a group of young patients (n = 1,383; median age 35.6 years) who recently acquired HIV by sexual contact, the majority of whom were HAART naïve, and comparing the performances of four HTLV confirmatory assays: LIA, WB, qPCR, and PCR-RFLP (tax). We confirmed HTLV infection in 58 (4.2%) blood samples: 29 HTLV-1, 24 HTLV-2, 1 HTLV-1+HTLV-2, and 4 HTLV. LIA, WB, qPCR, and PCR-RFLP sensitivities were 94.8%, 82.8%, 79.2%, and 74.5%, respectively. Associations of HTLV infection with female gender (OR = 2.28, 1.31-4.00) and age >40 years (p < .0001) were detected. The results confirm the low sensitivities of molecular assays and the best performance of LIA in detecting HTLV-1/2 in such patients. We hypothesize that the negative PCR results are due to the presence of defective provirus and/or low proviral load circulating in such patients, with inconclusive WB coinciding with the seroconversion period. Corroborating the associations obtained, repeated exposure is required for HTLV sexual transmission/acquisition, which is more efficient from male to female.

Surveillance of human retroviruses in blood samples from patients with hepatitis B and C in São Paulo, Brazil

“…The same services and regions accounted for the positive HTLV-1/2 results in both the HCV-and HBV-infected individuals. The percentages of HTLV-1/2 detected herein were of concern as they were similar to those detected in an HTLV-endemic area (1.8%) 20 and in populations with HIV/AIDS from São Paulo (3.1% to 4.2%) [21][22][23] .…”

Line Immunoassay for Confirmation and Discrimination of Human T-Cell Lymphotropic Virus Infections in Inconclusive Western Blot Serum Samples from Brazil

“…Of note, the reasons described above to explain WB-inconclusive results could also be applied to the PCR-negative results in truly HTLV-1/2-infected individuals, including the low proviral loads in HIV/AIDS patients undergoing antiretroviral therapy in G1 and, in some cases, in G2 (13)(14)(15); the observation that HTLV-2 infection is known to show low proviral loads (11,12,25); the presence of defective provirus not detected by the primers employed in the PCR assays (27); and infection with other viruses, such as HTLV-3 or HTLV-4, which can be detected only by using specific primers (36,37).…”

“…The serum samples employed in the present study were obtained from the biorepositories of the HTLV Research Laboratory (LPHTLV), Department of Immunology, Adolfo Lutz Institute (IAL), located in São Paulo, Brazil, and the Integrated and Multidisciplinary HTLV Center (CHTLV), located at the Bahiana School of Medicine and Public Health (EBMSP) in Salvador, Bahia, Brazil. Briefly, the samples from São Paulo were collected between 2012 and 2016 in the course of previous studies designed to detect the prevalence of HTLV-1/2 in HIV-infected individuals as well as in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in the state of São Paulo, Brazil (14,15,(18)(19)(20). The samples from Salvador, Bahia, were obtained by routine diagnostic procedures at an outpatient clinic in Salvador (CHTLV) from 2015 to 2017; these samples were additionally used to assess the performances of four commercially available HTLV serological screening tests in Brazil (21).…”

“…Nonetheless, there was no consensus regarding the criteria to consider a blood sample truly infected by HTLV-1/2 using these techniques if positive for one or at least two DNA proviral segments of HTLV-1/2 (6,10,11). Subsequently, another molecular assay, real-time PCR or quantitative PCR (qPCR), was proposed as a confirmatory HTLV-1/2 molecular assay; however, low sensitivity was found when applied on HIV blood samples and on those from Brazilian patients infected with HTLV-2, which could be due to low HTLV-2 proviral loads (12)(13)(14)(15).…”

“…However, the high cost of INNO-LIA prevented its routine adoption in Brazil. Consequently, few studies have compared the performances of LIA and WB in Brazil, one employing blood bank samples (17) and two using serum samples from HIV/AIDS patients (14,15). These studies indicated that the LIA was the best assay to confirm or rule out HTLV-1/2 infection.…”