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Background: The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma., Aims and Methodology: This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records., Key Results: Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17-5.99)]., Major Conclusions: HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Human retroviruses and the hepatitis B and C viruses (HBV and HCV, respectively) share routes of transmission; thus, coinfections occur and could alter subsequent disease outcomes. A preliminary study on human T-lymphotropic virus types 1 and 2 (HTLV-1/2) in serum samples from HBV- and HCV-infected individuals in São Paulo revealed 1.3% and 5.3% rates of coinfection, respectively. These percentages were of concern since they were detected in HTLV-endemic regions and in high-risk individuals in Brazil. The present study was conducted to extend and confirm these data., Methods: HTLV-1/2 and human immunodeficiency virus (HIV) infection status were identified in 1,984 sera for HBV and HCV viral load quantification - 1,290 samples from HBV-infected individuals (53.3% men, mean age: 47.1 years) and 694 samples from HCV-infected individuals (56.3% men, mean age: 50.1 years). HTLV-1/2 antibodies were detected by enzyme immunoassay, followed by western blotting and line immunoassay; HIV infection was detected by enzyme immunoassay., Results: HTLV-1/-2 infection was detected in 1.9% HBV-infected individuals (0.7% HTLV-1 and 1.2% HTLV-2) and in 4.0% (2.4% HTLV-1 and 1.6% HTLV-2) HCV-infected individuals; HIV infection was detected in 9.2% and 14.5%, respectively. Strong associations with HTLV and HIV, male sex, and older age were found in HBV/HTLV and HCV/HTLV-coinfected individuals (p<0.05)., Conclusions: HTLV-1 and HTLV-2 were confirmed to be prevalent in individuals with HBV and HCV in São Paulo; coinfected individuals deserve further clinical and laboratory investigation.

Identifying the true prevalence of human T-cell lymphotropic virus, mostly type 1 (HTLV-1), and the number of patients with HTLV-1-associated diseases, in addition to introducing HTLV-1/2 serology during the prenatal of pregnant women and in individuals infected with other viruses that share transmission routes with HTLV-1, are actions that could help to recognize the importance of this virus by WHO and national health organizations, and to control its transmission/dissemination. As Brazil is endemic to HTLV and there is an increase in health care expenditure, but resources are limited, any strategy that could reduce the cost of HTLV screening is needed and welcomed. This study aimed to determine whether the strategy of pooling sera for HTLV antibody determination is feasible and reduces the costs. Two enzyme immunoassays (EIA Murex HTLV-I+II, Diasorin, UK, and Gold ELISA HTLV-1+2, REM Ind. Com. Ltda., SP, Brazil), and serum samples that resulted in different levels of HTLV-1/2 antibodies by EIA and of which a volume allowed assay validation were employed for analysis. The diagnostic sensitivity and specificity and Cohen's Kappa value, as well as the accuracy and precision were analyzed. After validating the five-sample pool using the EIA Murex (Cohen's Kappa = 1.0), the technique was employed for individual cost comparison in 2,625 serum samples from populations at risk of HTLV infections (HBV, HCV, and HIV-infected individuals). The results from individual and pooled samples confirmed the diagnostic sensitivity (100%) and specificity (100%) of the pooling and a cost minimization varying from 60.7% to 73.6%. In conclusion, the results of this study suggest the use of pooling sera in sero-epidemiological surveillance studies and possibly in prenatal care screening programs in Brazil.

Santa Catarina is a Brazilian State that has reported the lowest prevalence of human T-cell lymphotropic viruses (HTLV-1/2) in blood donors (0.04%). Although it presents ports, airports and roads that facilitate the entrance and dissemination of new infectious agents, no information exists concerning the HTLV-1/2 infections in HIV/AIDS patients. This study searched for HTLV-1/2 antibodies in plasma samples of 625 HIV/AIDS patients from the municipality of Tubarao (Southern Santa Catarina), and disclosed 1.1% of positivity (0.48% HTLV-1, 0.48% HTLV-2 and 0.16% untypeable HTLV), and a positive correlation with the male sex (OR 4.16) and intravenous drug use (OR 35.18). Although the percentage of 1.1% appears to be low, it is 27.5 times higher than the percentage detected in blood donors. Since HTLV-1 and HTLV-2 are circulating in HIV-infected individuals in Southern Santa Catarina, and these retroviruses could cause a differently impact on the HIV/AIDS outcomes, the surveillance of HTLV-1/2 is necessary, and it could support public health policies in preventing the transmission and dissemination of these viruses in this State.

Co-infections of hepatitis C virus (HCV) and either human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type 1 (HTLV-1) or type 2 (HTLV-2) have been described as having an impact on HCV viremia and subsequent disease progression. HCV load in serum samples from 622 patients (343 males, 279 females; median age 50.8 years) from São Paulo/southeast Brazil was analyzed using the Abbott Real Time HCV assay (Abbott Molecular Inc., IL, USA). Samples were obtained from HCV-monoinfected (n=548), HCV/HIV-1- (n=41), HCV/HTLV-1- (n=16), HCV/HTLV-2- (n=8), HCV/HIV/HTLV-1- (n=4), and HCV/HIV/HTLV-2-co-infected (n=5) patients, and results were compared among the groups and according to sex. The median HCV load in HCV-monoinfected patients was 5.23 log 10 IU/mL and 0.31 log 10 higher in men than in women. Increases in viral load of 0.51 log 10 , 0.54 log 10 , and 1.43 log 10 IU/mL were detected in HCV/HIV-1-, HCV/HTLV-1- and HCV/HIV/HTLV-1-co-infected individuals, respectively, compared with HCV-monoinfected counterparts. In contrast, compared to HCV/HIV co-infected patients, HCV/HTLV-2-co-infected patients had an HCV load of 5.0 log 10 IU/mL, whereas HCV/HIV/HTLV-2-co-infected patients had a median load 0.37 log 10 IU/mL lower. Significant differences in HCV loads were detected, with males and HCV/HIV-1- and HCV/HIV/HTLV-1-co-infected patients presenting the highest values. Conversely, females and HCV/HTLV-2-co-infected patients exhibited lower HCV loads. Overall, HCV viremia is increased in HIV and/or HTLV-1-co-infection and decreased in HTLV-2 co-infection., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

With this study, the authors hope to alert clinicians regarding the presence of human T-cell lymphotropic virus type 1 and 2 (HTLV-1/-2) infections in patients with viral hepatitis B and C in Brazil. HTLV-1/-2 were detected in 1.3% of hepatitis B virus (HBV)- and 5.3% of hepatitis C virus (HCV)-infected blood samples sent for laboratory viral load measurements. A partial association of human immunodeficiency virus (HIV)-1 and HTLV-1/-2 infection was detected in patients with HCV (HIV+, 27.3%), whereas this association was almost 100% in HBV-infected patients (HIV+, all except one). The high prevalence of HTLV-1/-2 infection among patients with hepatitis C was of concern, as HTLV-1/-2 could change the natural course of subsequent liver disease. The authors suggest including HTLV-1/-2 serology in the battery of tests used when following patients with viral hepatitis in Brazil, regardless of the HIV status.

The present study evaluated several techniques currently available (commercial kits and in-house assays) for diagnosing human T lymphotropic viruses types 1 and 2 in two groups of patients enrolled at HIV/AIDS specialized care services in São Paulo: Group 1 (G1), n=1608, 1237 male/371 female, median age 44.3 years old, majority using highly active antiretroviral therapy (HAART); G2, n=1383, 930 male/453 female, median age of 35.6 years old, majority HAART naïve. Enzyme immunoassays [(EIA) Murex and Gold ELISA] were employed for human T lymphotropic viruses types 1 and 2 screening; Western blotting (WB), INNO-LIA (LIA), real-time PCR pol (qPCR), and nested-PCR-RFLP (tax) were used to confirm infection. Samples were considered human T lymphotropic viruses types 1 and 2 positive when there was reactivity using at least one of the four confirmatory assays. By serological screening, 127/2991 samples were positive or borderline, and human T lymphotropic virus infection was confirmed in 108 samples (three EIA-borderline): 56 human T lymphotropic virus type 1 [G1 (27)+G2 (29)]; 45 human T lymphotropic virus type 2 [G1 (21)+G2 (24)]; one human T lymphotropic virus type 1+human T lymphotropic virus type 2 (G2); six human T lymphotropic virus [G1 (2)+G2 (4)]. Although there were differences in group characteristics, human T lymphotropic viruses types 1 and 2 prevalence was similar [3.1% (G1) and 4.2% (G2), p=0.113]. The overall sensitivities of LIA, WB, qPCR, and PCR-RFLP were 97.2%, 82.4%, 68.9%, and 68.4%, respectively, with some differences among groups, likely due to the stage of human T lymphotropic virus infection and/or HAART duration. Indeterminate immunoblotting results were detected in G2, possibly due to the seroconversion period. Negative results in molecular assays could be explained by the use of HAART, the occurrence of defective provirus and/or the low circulating proviral load. In conclusion, when determining the human T lymphotropic virus infection, the findings highlight that there is a need to consider the blood samples with borderline results in screening assays. Of all the tested assays, LIA was the assay of choice for detecting human T lymphotropic virus type 1 and human T lymphotropic virus type 2 in human immunodeficiency virus type 1-infected patients., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

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.

During the 1990s, high prevalences of HIV/human T lymphotropic virus type 1 (HTLV-1) and HIV/human T lymphotropic virus type 2 (HTLV-2) coinfections were detected in São Paulo, Brazil in association with intravenous drug use (IDU). The current prevalences and risk factors for HIV/HTLV-1/-2 were evaluated in 1,608 patients attending the AIDS/STD Reference and Training Center in São Paulo. Blood samples were analyzed for HTLV-1/2-specific antibodies using enzyme immunoassays (EIA Murex HTLV-I+II, Diasorin, and Gold ELISA HTLV-I+II, REM) and immunoblotting (HTLV Blot 2.4, MP Biomedicals and INNO-LIA HTLV-I/II, Innogenetics) and for the pol proviral DNA segments of HTLV-1 and HTLV-2 by "in-house" real-time PCR. These analyses revealed that 50 (3.11%) of the samples were HTLV positive, including 25 (1.55%) that were HTLV-1 positive, 21 (1.31%) that were HTLV-2 positive, and 4 (0.25%) that were HTLV positive (untypeable). The median age of the HIV/HTLV-coinfected individuals was 50 years versus 44 years in the overall population (p=0.000). The risk factors associated with HIV/HTLV-1/-2 coinfections were female gender (OR 3.26, 1.78-5.95), black/pardo color (OR 2.21, 1.21-4.03), infection with hepatitis B virus (HBV) (OR 4.27, 2.32-7.87) or hepatitis C virus (HCV) (OR 24.40, 12.51-48.11), and intravenous drug use (IDU) (OR 30.01, 15.21-59.29). The current low prevalence of HTLV-1/2 in HIV-infected patients in São Paulo could be explained in part by programs providing IDUs with sterile needles and syringes and changes in the drug usage patterns of individuals from injecting cocaine to smoking crack cocaine.