A novel high performing multiplex immunoassay Multi-HTLV for serological confirmation and typing of HTLV infections.

BACKGROUND: Human T-Cell Lymphotropic Viruses (HTLV) type 1 and type 2 account for an estimated 5 to 10 million infections worldwide and are transmitted through breast feeding, sexual contacts and contaminated cellular blood components. HTLV-associated syndromes are considered as neglected diseases for which there are no vaccines or therapies available, making it particularly important to ensure the best possible diagnosis to enable proper counselling of infected persons and avoid secondary transmission. Although high quality antibody screening assays are available, currently available confirmatory tests are costly and have variable performance, with high rates of indeterminate and non-typable results reported in many regions of the world. The objective of this project was to develop and validate a new high-performance multiplex immunoassay for confirmation and discrimination of HTLV-1 and HTLV-2 strains. METHODOLOGY/PRINCIPAL FINDINGS: The multiplex platform was used first as a tool to identify suitable antigens and in a second step for assay development. With data generated on over 400 HTLV-positive blood donors sourced from USA and French blood banks, we developed and validated a high-precision interpretation algorithm. The Multi-HTLV assay demonstrated very high performance for confirmation and strain discrimination with 100% sensitivity, 98.1% specificity and 100% of typing accuracy in validation samples. The assay can be interpreted either visually or automatically with a colorimetric image reader and custom algorithm, providing highly reliable results. CONCLUSIONS/SIGNIFICANCE: The newly developed Multi-HTLV is very competitive with currently used confirmatory assays and reduces considerably the number of indeterminate results. The multiparametric nature of the assay opens new avenues to study specific serological signatures of each patient, follow the evolution of infection, and explore utility for HTLV disease prognosis. Improving HTLV diagnostic testing will be critical to reduce transmission and to improve monitoring of seropositive patients.

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies.

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

Prevalence of human T-lymphotropic virus type 1 and 2 (HTLV-1/-2) infection in pregnant women in Brazil: a systematic review and meta-analysis.

Human T-lymphotropic virus type 1 (HTLV-1) infection may cause serious disease, while pathogenicity of HTLV-2 is less certain. There are no screening or surveillance programs for HTLV-1/-2 infection in Brazil. By performing this systematic review, we aimed to estimate the prevalence of HTLV-1/-2 infections in pregnant women in Brazil. This review included cohort and cross-sectional studies that assessed the presence of either HTLV-1/-2 infection in pregnant women in Brazil. We searched BVS/LILACS, Cochrane Library/CENTRAL, EMBASE, PubMed/MEDLINE, Scopus, Web of Science and gray literature from inception to August 2020. We identified 246 records in total. Twenty-six of those were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. The prevalence of HTLV-1 in Brazilian pregnant women, as diagnosed by a positive screening test and a subsequent positive confirmatory test, was 0.32% (95% CI 0.19-1.54), while of HTLV-2 was 0.04% (95% CI 0.02-0.08). Subgroup analysis by region showed the highest prevalence in the Northeast region (0.60%; 95% CI 0.37-0.97) for HTLV-1 and in the South region (0.16%; 95% CI 0.02-1.10) for HTLV-2. The prevalence of HTLV-1 is much higher than HTLV-2 infection in pregnant Brazilian women with important differences between regions. The prevalence of both HTLV-1/-2 are higher in the Northeast compared to Center-West region.

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection.

Laboratory diagnosis of human T-lymphotropic viruses (HTLV) 1 and 2 infection is performed by serological screening and further confirmation with serological or molecular assays. Thus, we developed a loop-mediated isothermal nucleic acid amplification (LAMP) assay for the detection of HTLV-1/2 in blood samples. The sensitivity and accuracy of HTLV-1/2 LAMP were defined with DNA samples from individuals infected with HTLV-1 (n = 125), HTLV-2 (n = 19), and coinfected with HIV (n = 82), and compared with real-time polymerase chain reaction (qPCR) and PCR-restriction fragment length polymorphism (RFLP). The overall accuracy of HTLV-1/2 LAMP (95% CI 74.8-85.5%) was slightly superior to qPCR (95% CI 69.5-81.1%) and similar to PCR-RFLP (95% CI 79.5-89.3%). The sensitivity of LAMP was greater for HTLV-1 (95% CI 83.2-93.4%) than for HTLV-2 (95% CI 43.2-70.8%). This was also observed in qPCR and PCR-RFLP, which was associated with the commonly lower HTLV-2 proviral load. All molecular assays tested showed better results with samples from HTLV-1/2 mono-infected individuals compared with HIV-coinfected patients, who present lower CD4 T-cell counts. In conclusion, HTLV-1/2 LAMP had similar to superior performance than PCR-based assays, and therefore may represent an attractive alternative for HTLV-1/2 diagnosis due to reduced working time and costs, and the simple infrastructure needed.

HTLV screening of blood donors using chemiluminescence immunoassay in three major provincial blood centers of China.

BACKGROUND: Human T-cell lymphotropic virus (HTLV) remains a major safety concern for blood supplies. Despite many HTLV positive cases being reported in southeastern China, the detection of HTLV has not been prioritized in routine blood screening. Additionally, data on the prevalence of HTLV infection among blood donors is also limited. The objective of this study was to investigate the prevalence of HTLV among blood donors in three Chinese provinces through their representative blood centers, to evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening. METHODS: From November 2018 to March 2019, blood plasma samples were collected from Hebei, Changsha, and Shenzhen blood centers and were screened for the HTLV-1/2 antibody using a CLIA and enzyme-linked immunosorbent assay (ELISA). This was followed by confirmatory tests using INNO-LIA HTLV I/II. RESULTS: A total of 59,929 blood donations were collected and screened for HTLV-1/2. The reactive rate of CLIA and ELISA among donations in the Shenzhen blood center (0.0943%, 27/28,621) was higher than Hebei (0.0248%, 4/16,144), and Changsha (0.0198%, 3/15,164) (p < 0.05). After confirmation, 3 samples were confirmed as indeterminate for HTLV antibodies, and only one sample from the Shenzhen blood center was confirmed as HTLV-1. The overall prevalence of HTLV-1/2 was 1.67 per 100,000 (1/59,929). The HTLV-infected blood came from a 32-year-old first-time female donor with a high school degree, who belonged to the SHE ethnic minority and was born in the Fujian province. CONCLUSIONS: In summary, the overall prevalence of HTLV-1/2 among blood donors in the three blood centers in China remains relatively low. However, blood donations with positive or indeterminate results for HTLV antibodies reminded us of the importance of HTLV screening among blood donors in China.

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

Difficulties in confirming and discriminating human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by serological Western blot (WB) assays (HTLV Blot 2.4; MP Biomedicals) have been reported in Brazil, mainly in HIV/AIDS patients, with a large number of WB-indeterminate and WB-positive but HTLV-untypeable results. Nonetheless, a line immunoassay (LIA) (INNO-LIA HTLV-I/II; Fujirebio) provided enhanced specificity and sensitivity for confirming HTLV-1/2 infections. To add information concerning the improved ability of the LIA in relation to WB when applied to samples of individuals from different risk groups from Brazil, we performed the present study. Three groups were analyzed: group 1 (G1), with 62 samples from HIV/AIDS patients from São Paulo, SP (48 WB indeterminate and 14 HTLV untypeable); group 2 (G2), with 24 samples from patients with hepatitis B or hepatitis C from São Paulo (21 WB indeterminate and 3 HTLV untypeable; 17 HIV seropositive); and group 3 (G3), with 25 samples from an HTLV outpatient clinic in Salvador, Bahia (16 WB indeterminate and 9 HTLV untypeable; all HIV seronegative). Overall, the LIA confirmed HTLV-1/2 infection (HTLV-1, HTLV-2, or HTLV) in 66.1% (G1), 83.3% (G2), and 76.0% (G3) of samples. Interestingly, the majority of WB-indeterminate results were confirmed by the LIA as being HTLV-2 positive in G1 and G2 but not in G3, in which the samples were defined as being HTLV-1 or HTLV positive. These results agree with the virus types that circulate in such patients of different regions in Brazil and emphasize that the LIA is the best serological test for confirming HTLV-1 and HTLV-2 infections, independently of being applied in HTLV-monoinfected or HTLV-coinfected individuals.

Silencers of HTLV-1 and HTLV-2: the pX-encoded latency-maintenance factors.

Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30II and HTLV-2 p28II, suppress Tax-dependent transactivation from the viral promoter-whereas p30II also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13II protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.

Pregnancy does not adversely impact diagnostic tests for HTLV-1/2 infection.

Mother-to-child-transmission (MTCT) of human T-cell lymphotropic virus type-1(HTLV-1) contributes disproportionately to the burden of HTLV-1 associated diseases. All preventive measures to avoid MTCT rely on the identification of infected mothers. However, the impact of pregnancy on HTLV-1 diagnosis has not been clearly assessed. Paired samples from 21 HTLV-1 infected women taken during pregnancy and while not pregnant were analysed by CMIA and PCR. The signal-to-cut-off values (S/CO) were higher during pregnancy than in the paired non-pregnant samples. HTLV-1 proviral load did not alter significantly by pregnant state. S/CO positively correlated with HTLV proviral load. Pregnancy does not impair the diagnosis of HTLV-1/2, by either immunological (CMIA) or molecular (qPCR/nPCR) tests.

Comparative virology of HTLV-1 and HTLV-2.

Human T cell leukemia virus type 1 (HTLV-1) was the first discovered human retrovirus and the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Shortly after the discovery of HTLV-1, human T-cell leukemia virus type 2 (HTLV-2) was isolated from a patient with hairy cell leukemia. Despite possession of similar structural features to HTLV-1, HTLV-2 has not been definitively associated with lymphoproliferative disease. Since their discovery, studies have been performed with the goal of highlighting the differences between HTLV-1 and HTLV-2. A better understanding of these differences will shed light on the specific pathogenic mechanisms of HTLV-1 and lead to novel therapeutic targets. This review will compare and contrast the two oldest human retroviruses with regards to epidemiology, genomic structure, gene products, and pathobiology.

Development and evaluation of human T-cell leukemia virus-1 and -2 multiplex quantitative PCR.

The diagnosis of human T -cell leukemia virus type 1 (HTLV-1) infection in Japan is usually performed by serological testing, but the high rate of indeterminate results from western blotting makes it difficult to assess the infection accurately. Nucleic acid tests for HTLV-1 and/or HTLV-2 are used to confirm infection with HTLV-1 and/or HTLV-2 and are also used for the follow-up of HTLV-1 related diseases. To prepare a highly sensitive method that can discern infection with HTLV-1 and HTLV-2, a multiplex quantitative polymerase chain reaction (qPCR) by large-scale primer screening was developed. Sensitivity and specificity were evaluated by serial dilution of cell lines and by testing with known clinical samples. The resulting multiplex qPCR can detect about four copies of HTLV-1 provirus per 105 cells. Moreover, HTLV-1 provirus could be detected in 97.2% (205 of 211) of HTLV-1 seropositive clinical samples. These sensitivities were sufficiently high compared with the methods reported previously. Also, all the HTLV-2 seropositive clinical samples tested were found to be positive by this method (three of three). In conclusion, this method can successfully and simultaneously detect both types of HTLV-1 and HTLV-2 provirus with extremely high sensitivity.

Dermatological manifestations in patients with human T-cell lymphotropic virus at a reference service in Amazon.

INTRODUCTION: Individuals infected with the human T-cell lymphotropic virus type 1 (HTLV-1) commonly present skin lesions, which may be a warning sign for the diagnosis of infection. This study describes the most prevalent skin manifestations in HTLV carriers attended at the clinic of Núcleo de Medicina Tropical (NMT) of the Universidade Federal do Pará (UFPA) in Belém, Pará, Brazil. METHODS: This is a study of a series of cases of patients infected with human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) treated at NMT UFPA between 1999 and 2016. A descriptive analysis of data was applied. RESULTS: Among 788 surveyed medical records in the service, 15.10% (n = 119) were referred to the dermatology clinic. From the series of cases that presented with skin lesions, 66.39% were female and 33.61% were male, and the average age of this group was 48 years. There was a predominance of patients with noninfectious inflammatory manifestations (64.2%), followed by infectious ones (24.6%), and 1.58% with lymphoproliferative diseases. As for the group of lesions, 45.26% of the erythematous-squamous type were observed, followed by dyschromia (24.21%), and eczematous (14.74%). One patient with a diagnosis of adult T-cell leukemia/lymphoma, another with parapsoriasis, and four with infective dermatitis are highlighted. CONCLUSION: Skin disorders in the HLTV positive patient are important causes of referral to the dermatologist with etiological and skin lesions groups diversity. In the series of cases studied, lymphoproliferatives diseases and infective dermatitis associated with HTLV-1 were presented as a challenge for the diagnosis and clinical management of these patients.

Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 2.

BACKGROUND: Human T-lymphotrophic virus (HTLV) types 1 and 2 cause lifelong infection whereby most infected individuals are asymptomatic whilst a minority develop infection-related disease. These latter patients invariably have been found to have high proviral load (PVL). Therefore, infected patients are monitored by determining the proportion of lymphocytes that are infected with HTLV-1/2. An increase in PVL has been shown to represent an increasing risk of developing HTLV-associated diseases. Monitoring of PVL requires a reliable and sensitive method. In this study assays based on droplet digital PCR (ddPCR) were established and evaluated for detection and quantification of HTLV-1/2. OBJECTIVES: To develop two parallel assays to detect the tax genes and determine the PVL of HTLV-1 and -2. STUDY DESIGN: Sixty-seven clinical samples from patients infected with HTLV-1 or HTLV-2 were analysed. The samples had previously been analysed with a qPCR and a comparison between ddPCR and qPCR was performed. The specificity of the assays were determined by analyzing samples from 20 healthy blood donors. RESULTS: The ddPCR was a stable and sensitive method for detection and quantification of HTLV-1 and -2. When comparing the qPCR and ddPCR the correlation was high (Pearsons correlation coefficient 0.96). The variability of the ddPCR was very low with intra-assay coefficient of variation (CV) of 0.97-3.3% (HTLV-1) and 1.7-8.2% (HTLV-2) and inter-assay CV of 1.8-6.1% (HTLV-1) and 1.2-12.9% (HTLV-2). CONCLUSIONS: The ddPCR reliably quantified HTLV DNA in clinical samples and could be a useful tool for monitoring of PVLs in HTLV-infected individuals.

Low prevalence of HTLV1/2 infection in a population of immigrants living in southern Italy.

AIMS: To assess the prevalence of HTLV-1 and HTLV-2 infections in a cohort of immigrants living in southern Italy. FINDINGS: We screened for antibody to HTLV-1/2 infection 1,498 consecutive immigrants born in endemic areas (sub-Saharan Africa or southern-Asia) by a commercial chemiluminescent microparticle immunoassay. If confirmed in a Western blot assay, which differentiates anti-HTLV-1 from anti-HTLV-2, the positive sera were tested for specific HTLV RNA by a home-made PCR. The immigrants investigated were more frequently males (89.05%), young (median age 26 years), with a low level of education (median schooling 6 years), born in sub-Saharan Africa (79.70%). They had been living in Italy for a median period of 5 months. Only one (0.07%) subject was anti-HTLV-1 -positive/HTLV-1 RNA-negative; he was an asymptomatic 27-year-old male from Nigeria with 6 years' schooling who stated unsafe sexual habits and unsafe injection therapy. CONCLUSIONS: The data suggest screening for HTLV1 and HTLV-2 infections all blood donors to Italy from endemic countries at least on their first donation; however, a cost-effectiveness study is needed to clarify this topic.

Hepatitis C viral load in HCV-monoinfected and HCV/HIV-1-, HCV/HTLV-1/-2-, and HCV/HIV/HTLV-1/-2-co-infected patients from São Paulo, Brazil.

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 log10 IU/mL and 0.31 log10 higher in men than in women. Increases in viral load of 0.51 log10, 0.54 log10, and 1.43 log10 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 log10 IU/mL, whereas HCV/HIV/HTLV-2-co-infected patients had a median load 0.37 log10 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.

Hepatitis C viral load in HCV-monoinfected and HCV/HIV-1-, HCV/HTLV-1/-2-, and HCV/HIV/HTLV-1/-2-co-infected patients from São Paulo, Brazil

ABSTRACT 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 log10 IU/mL and 0.31 log10 higher in men than in women. Increases in viral load of 0.51 log10, 0.54 log10, and 1.43 log10 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 log10 IU/mL, whereas HCV/HIV/HTLV-2-co-infected patients had a median load 0.37 log10 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.

Prevalence of Human T-lymphotropic virus type 1 and 2 among blood donors in Manaus, Amazonas State, Brazil.

INTRODUCTION: Human T-lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in Brazil, but few studies have investigated the seroprevalence of HTLV and its subtypes among blood donors in the capital city Manaus, Amazonas State, Brazil. AIM: To estimate the seroprevalence of HTLV-1/2 and to identify circulating subtypes among blood donors in Manaus. MATERIALS AND METHODS: Blood donors (2001-2003) were screened for HTLV-1/2 antibodies by ELISA. Positive results were confirmed and subtyped by Western blot assays. Prevalence rates were calculated and compared with demographic data. RESULTS: Among the 87,402 individuals screened, 116 (0.13%) were seropositive for HTLV-1/2. A second sample (76/116) was collected and retested by HTLV-1/2 ELISA, of which only 41/76 were positive. Western blot confirmed HTLV infection in 24/41 retested blood donors [HTLV-1 (n=16), HTLV-2 (n=5) and HTLV-untypable (n=3)]. DISCUSSION: HTLV-1 and HTLV-2 are prevalent among blood donors in Manaus. However, additional studies are needed to comprehend the epidemiology of HTLV-1/2 in Amazonas not only to understand the pathophysiology of the disease providing adequate medical assistance, but also to reduce or block virus transmission.

Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010-2014.

BACKGROUND: Retroviruses of human T-lymphotropic viruses (HTLV-1 and HTLV-2) have been demonstrated to be endemic in the north-eastern region of Iran. This study was aimed to determine the HTLV-1 and HTLV-2 prevalence among healthy individuals in Neyshabur City during 2010-2014. METHODS: A total of 8054 blood samples were collected from healthy participants in Neyshabur, North-Eastern Iran. The blood samples were screened for the presence of specific antibodies against HTLV-1 and HTLV-2 by using ELISA according to the manufacturer's instructions. RESULTS: The overall seropositivity rate for HTLV-1 and HTLV-2 was found to be 6.55% (528 out of 8054) among participants. CONCLUSION: Both HTLV-1 and HTLV-2 were demonstrated to be at a high rate in healthy individuals. However, a smaller number of asymptomatic carriers were found in this study, as compared to those identified in previous investigations in the city.

Delayed Seroconversion to HTLV-II Is Associated with a Stop-Codon Mutation in the pol Gene.

A known HIV-1-positive intravenous drug user was found to be human T cell lymphoma/leukemia virus-II (HTLV-II) DNA positive by polymerase chain reaction but seronegative in a screening ELISA. He was consistently DNA positive but took 2 years to fully seroconvert. Sequencing of the HTLV-II strain in his cultured T lymphocytes indicated that it is a prototypical type A strain with no major differences in the long terminal repeat DNA sequence, nor major amino acid differences in the Gag, Env, Tax, and Rex proteins. However, a mutation in its pol gene created a stop codon at amino acid 543 of the Pol protein, a region that encodes for the RNase function. This mutation may account for the subject's slow seroconversion.

Human T-lymphotropic Virus Co-infections in Adults Infected With Human Immunodeficiency Virus.

INTRODUCTION: Human T-lymphotropic virus type 1 or 2 (HTLV-1/2) co-infection in patients infected with the human immunodeficiency virus (HIV) can lead to increased morbidity. Because HTLV-1/2 shares a similar transmission route with HIV, HTLV-1/2 infection may be more prevalent in HIV-infected individuals. However, rates of HTLV-1/2 co-infection among HIV-infected individuals have not been studied recently in the United States. MATERIALS AND METHODS: We conducted a cross-sectional study using serum from 292 HIV-infected subjects from one clinic in Virginia. Serum samples were tested for co-infection with HTLV-1/2 by commercial ELISA; positive results were then confirmed via western blot, which also differentiated between HTLV-1 and -2. RESULTS: Seven (2.4%) of the subjects were co-infected with HTLV-2. One subject (among the seven co-infected with HTLV-2) was co-infected with HTLV-1 (0.3%). The only demographic factor significantly associated with HTLV-2 infection was history of intravenous drug abuse (p=0.002). CONCLUSIONS: While our results are limited to a single city, our low rates of co-infection do not support routine screening for HTLV-1/2 co-infection among HIV-infected individuals in the United States.