Detection of human T-cell lymphotropic virus type 1 in plasma samples.

Human T-cell lymphotropic virus type 1 (HTLV-1) is an RNA virus responsible for diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATL). Cell-to-cell contact and Tax-induced clonal expansion of infected cells are the main modes of virus replication, making virus detection during the viremic stage difficult. Consequently, the proviral load is the current virologic marker for disease monitoring, but the mechanisms of progression have not been established yet. Thus, this study investigated the presence of virus in plasma from asymptomatic HTLV-1 carriers and from HAM/TSP patients. Real-time PCR was performed on DNA from 150 plasma samples; 12 (8%) had detectable DNA amplification, including 6 (4%) asymptomatic HTLV-1 carriers and 14 (26%) HAM/TSP patients (p<0.005). Of the 33 samples submitted for nested PCR, six (18%, p=0.02) were positive for HTLV-1 RNA in the plasma. Additionally, 26 plasma samples were treated with DNAse enzyme to eliminate any DNA contamination before RNA extraction. Two of them (8%) showed amplification for HTLV-1 (p=0.5). Therefore, this study described for the first time the detection of free HTLV-1 RNA in plasma from HTLV-1-infected subjects, regardless of their clinical status. Thus, HTLV-1 viral replication does occur in plasma, and other transmission pathways for HTLV-1 should be investigated further.

Low DNA HTLV-2 proviral load among women in São Paulo City.

BACKGROUND: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HIV-1 co-infection. METHODS: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. RESULTS: Six of 53HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 copies/10(4) PBMCs, p<0.05). CONCLUSIONS: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus.

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients.

UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and -2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co-infected subjects may be at increased risk for tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)-like. To study the prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) among co-infected HIV-1/HTLV-1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV-1-infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas," in São Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. RESULTS: A total of 38 HIV-1/HTLV-1 co-infected subjects were identified in this cohort: Twenty-six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co-infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow-up. No modifications on HIV-1 viral load was seen. In contrast, the co-infected with TSP/HAM-like group showed higher HTLV-1 proviral load (505 +/- 380 vs. 97 +/- 149 copies/10(4) PBMC, P = 0.012) than asymptomatic co-infected subjects, respectively. The incidence of myelopathy among HIV-1/HTLV-1 co-infected subjects is probably higher than among patients infected only with HTLV-1, and related to a higher HTLV-1 proviral load. Thus, HTLV-1/2 screening should be done for all HIV-1-infected patients in areas where HTLV-1 infection is endemic.

T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): high prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM).

INTRODUCTION: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4+ cell counts, thus rendering this parameter useless as an AIDS-defining event. OBJECTIVE: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4+ cells. MATERIAL AND METHODS: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB) or polymerase chain reaction (PCR). All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO) classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC) classification of 1988. The first T CD4+ cells count available before starting anti-retroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. RESULTS: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4+ cell counts was 189 (98-688) cells/mm(3) and 89 (53-196) cells/mm(3) for co-infected subjects who had an AIDS-defining event, and HIV-only infected individuals, respectively (p = 0.036). Eight of 27 co-infected subjects (30%) were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4+ cell counts at the time of their AIDS- defining event. DISCUSSION: Our results indicate that higher T CD4+ cells count among HIV-1/HTLV-1-coinfected subjects was found in 12% of the patients who presented an AIDS-defining event. These subjects also showed a TSP/HAM simile picture when it was the first manifestation of disease; this incidence is 20 times higher than that for HTLV-1-only infected subjects in endemic areas.

T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): high prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)

INTRODUCTION: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4+ cell counts, thus rendering this parameter useless as an AIDS-defining event. OBJECTIVE: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4+ cells. MATERIAL AND METHODS: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB) or polymerase chain reaction (PCR). All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO) classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC) classification of 1988. The first T CD4+ cells count available before starting anti-retroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. RESULTS: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4+ cell counts was 189 (98-688) cells/mm³ and 89 (53-196) cells/mm³ for co-infected subjects who had an AIDS-defining event, and HIV-only infected individuals, respectively (p = 0.036). Eight of 27 co-infected subjects (30 percent) were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4+ cell counts at the time of their AIDS- defining event. DISCUSSION: Our results indicate that...

INTRODUÇÃO: A possibilidade que a co-infecção pelo vírus da leucemia de células T humana do tipo 1 (HTLV-1) em indivíduos infectados pelo vírus da imunodeficiência humana do tipo 1 poderia falsamente elevar o número de linfócitos T CD4+ no momento do evento definidor de aids, inferindo que essa contagem poderia ser um marcador laboratorial incompleto nos pacientes com a co-infecção HIV-1/HTLV-1. OBJETIVO: Estudar a interação entre o HIV-1 e a co-infecção como o HTLV-1. MATERIAL E MÉTODO: Desde 1997, nosso grupo tem seguido uma coorte de pacientes para estudar a interação entre HIV e/ou vírus da hepatite C (HCV), como também pacientes assintomáticos ou com TSP/HAM. 150 pacientes infectados pelo HTLV-1, encaminhados à clínica de HTLV do Instituto de Infectologia Emilio Ribas, São Paulo, Brasil, foram estudados. Vinte e sete deles estavam co-infectados pelo HIV-1 e HTLV-1, usando dois ELISAs e confirmados tipados pelo WB ou PCR. Todos os pacientes foram avaliados por dois neurologistas, cegos para o status de HTLV e o diagnóstico de TSP/HAM foi baseado na classificação da Organização Mundial de Saúde, 1988. A primeira contagem de células T disponível antes da terapia anti-retroviral foi mostrada para comparar com os pacientes infectados pelo HIV no momento do evento definidor de aids de acordo com Classificação do Centro de controle de Doenças, 1988. RESULTADOS: Um total de 27 HIV-1/HTLV-1 co-infectados foram identificados na coorte, 15 já apresentavam aids e 12 permaneceram sem evento de aids. A mediana de células T CD4 foi de 189 (98-688) células/mm³ e 89 (53-196) células/mm³ nos co-infectados que tinham evento definidor de aids e naqueles com a infecção somente pelo HIV, respectivamente (p = 0,036). Oito dos 27 co-infectados (30 por cento) foram diagnosticados tendo TSP/HAM símile, e três deles mostraram elevada contagem de células T CD4 e apresentaram infecções oportunistas no momento do evento definidor de aids. DISCUSSÃO: Nossos resultados...

High production of RANTES and MIP-1alpha in the tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM).

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with progressive neurological disorders and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). The pathogenesis of TSP/HAM is considered as immune mediated, involving cytotoxic T cell (CTL) responses to a number of viral proteins and notably the regulation protein Tax. T CD8+ cells produce beta-chemokines, which are important in the anti-viral response. In the present study, we have analyzed the CC chemokines (RANTES, MIP-1beta and MIP-1alpha) production in retrovirus-infected subjects. A total of 191 subjects were studied: 52 healthy controls, 72 asymptomatic HTLV-1-infected carriers and 67 TSP/HAM patients. Peripheral blood mononuclear cells were maintained in the presence or absence of PHA, and supernatant fluids were assayed using EIA. MIP-1beta concentration was not significantly different across groups, but RANTES and MIP-1alpha concentrations showed significant differences when the three groups were compared. In TSP/HAM patients, the increase in the production of chemokines may lead to a recruitment of pro-inflammatory factors, contributing to the membrane's myelin damage.

Clinical and epidemiological aspects of HTLV-II infection in São Paulo, Brazil: presence of tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile diagnosis in HIV-1-co-infected subjects.

In this study, the epidemiological and clinical features observed in solely HTLV-II-infected individuals were compared to those in patients co-infected with HIV-1. A total of 380 subjects attended at the HTLV Out-Patient Clinic in the Institute of Infectious Diseases "Emilio Ribas" (IIER), São Paulo, Brazil, were evaluated every 3-6 months for the last seven years by infectious disease specialists and neurologists. Using a testing algorithm that employs the enzyme immuno assay, Western Blot and polymerase chain reaction, it was found that 201 (53%) were HTLV-I positive and 50 (13%) were infected with HTLV-II. Thirty-seven (74%) of the HTLV-II reactors were co-infected with HIV-1. Of the 13 (26%) solely HTLV-II-infected subjects, urinary tract infection was diagnosed in three (23%), one case of skin vasculitis (8%) and two cases of lumbar pain and erectile dysfunction (15%), but none myelopathy case was observed. Among 37 co-infected with HIV-1, four cases (10%) presented with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile. Two patients showed paraparesis as the initial symptom, two cases first presented with vesical and erectile disturbances, peripheral neuropathies were observed in other five patients (13%), and seven (19%) patients showed some neurological signal or symptoms, most of them with lumbar pain (five cases). The results obtained suggest that neurological manifestations may be more frequent in HTLV-II/HIV-1-infected subjects than those infected with HTLV-II only.

Clinical and epidemiological aspects of HTLV-II infection in São Paulo, Brazil: presence of Tropical Spastic Paraparesis/HTLV-Associated Myelopathy (TSP/HAM) simile diagnosis in HIV-1-co-infected subjects / Aspectos clínicos e epidemiológicos da infecção pelo vírus linfotrópico de células T humanas do tipo 2 (HTLV-II) em São Paulo, Brasil: presença de paraparesia espástica tropical/mielopatia associada ao HTLV em pacientes co-infectados pelo HIV-1

In this study, the epidemiological and clinical features observed in solely HTLV-II-infected individuals were compared to those in patients co-infected with HIV-1. A total of 380 subjects attended at the HTLV Out-Patient Clinic in the Institute of Infectious Diseases "Emilio Ribas" (IIER), São Paulo, Brazil, were evaluated every 3-6 months for the last seven years by infectious disease specialists and neurologists. Using a testing algorithm that employs the enzyme immuno assay, Western Blot and polymerase chain reaction, it was found that 201 (53 percent) were HTLV-I positive and 50 (13 percent) were infected with HTLV-II. Thirty-seven (74 percent) of the HTLV-II reactors were co-infected with HIV-1. Of the 13 (26 percent) solely HTLV-II-infected subjects, urinary tract infection was diagnosed in three (23 percent), one case of skin vasculitis (8 percent) and two cases of lumbar pain and erectile dysfunction (15 percent), but none myelopathy case was observed. Among 37 co-infected with HIV-1, four cases (10 percent) presented with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile. Two patients showed paraparesis as the initial symptom, two cases first presented with vesical and erectile disturbances, peripheral neuropathies were observed in other five patients (13 percent), and seven (19 percent) patients showed some neurological signal or symptoms, most of them with lumbar pain (five cases). The results obtained suggest that neurological manifestations may be more frequent in HTLV-II/HIV-1-infected subjects than those infected with HTLV-II only.

Neste estudo, as características epidemiológicas e clínicas observadas nos indivíduos infectados pelo HTLV-II foram comparadas com os pacientes co-infectados com HIV-1. Um total de 380 indivíduos atendidos na clínica do Ambulatório HTLV do Instituto de Infectologia "Emilio Ribas" (IIER), São Paulo, Brasil, foram avaliados a cada 3-6 meses nos últimos sete anos por especialistas em doenças infecciosas e neurologistas. Usando um algoritmo que emprega ensaio imunoenzimático, Western Blot e reação em cadeia de polimerase, foram incluídos 201 (53 por cento) pacientes infectados pelo HTLV-I e 50 (13 por cento) infectados pelo HTLV-II. Trinta e sete (74 por cento) eram co-infectados pelo HTLV-II e HIV-1. Dos 13 (26 por cento) indivíduos unicamente infectados pelo HTLV-II, infecção do trato urinário foi diagnosticada em três, um com vasculite e em dois casos dor lombar e disfunção erétil mas nenhum caso de mielopatia foi observado. Entre 37 pacientes co-infectados com HIV-1, quatro (10 por cento) casos apresentaram com paraparesia espástica tropical/mielopatia associada ao HTLV similar. Dois casos mostraram paraparesia como sintoma inicial, dois outros casos se apresentaram primeiramente com distúrbios vesical e erétil e as neuropatias periféricas foram observadas em cinco pacientes (13 por cento). Outros sete (19 por cento) pacientes mostraram algum sinal ou sintoma neurológico, a maioria deles com dor lombar (cinco casos). Os resultados sugerem que as manifestações neurológicas podem ser mais freqüentes em indivíduos co-infectados pelo HTLV-II/HIV-1 do que nos indivíduos infectados somente pelo HTLV-II.

Human immunodeficiency virus type 1 Brazilian subtype B variant showed an increasing avidity of the anti-V3 antibodies over time compared to the subtype B US/European strain in São Paulo, Brazil.

The Brazilian variant of human immunodeficiency virus type 1 (HIV-1) subtype B, (serotype B"-GWGR), has a tryptophan replacing the proline in position 328 the HIV-1 envelope. A longer median time period from infection to acquired immunodeficiency syndrome (AIDS) for serotype B (B"-GWGR) infected subjects compared to the B-GPGR US/European strain was reported. In a cohort study, in São Paulo city, 10 B"-GWGR patients had a statistically significant increased avidity of the anti-V3 antibodies, from 79% +/- 33% to 85% +/- 75%, versus from 48% +/- 59% to 32% +/- 17% for the 10 B-GPGR subjects (p = 0.02). The T CD4+ cells showed a mean increase of + 0.45 cells/month for the B-GPGR subjects and for B"-GWGR the slope was + 1.24 cells/month (p = 0.06), for 62 and 55 months of follow up, respectively. RNA plasma viral load decreased from 3.98 +/- 1.75 to 2.16 +/- 1.54 log10 in the B"-GWGR group while B-GPGR patients showed one log10 reduction in viral load from 4.09 +/- 0.38 to 3.17 +/- 1.47 log10 over time (p = 0.23), with a decreasing slope of 0.0042 +/- log10,/month and 0.0080 +/- log10/month, for B-GPGR and B"-GWGR patients, respectively (p = 0.53). Neither group presented any AIDS defining events during the study, according to Center for Diseases Control criteria. Although the sample size is small, these results may indicate that differences in the pathogenicity of the 2 HIV-1 B serotypes which co-circulate in Brazil may be correlated to the avidity of anti-V3 antibodies.

Human immunodeficiency virus type 1 Brazilian subtype B variant showed an increasing avidity of the anti-V3 antibodies over time compared to the subtype B US: European strain in São Paulo, Brazil

The Brazilian variant of human immunodeficiency virus type 1 (HIV-1) subtype B, (serotype B"-GWGR), has a tryptophan replacing the proline in position 328 the HIV-1 envelope. A longer median time period from infection to acquired immunodeficiency syndrome (AIDS) for serotype B (B"-GWGR) infected subjects compared to the B-GPGR US/European strain was reported. In a cohort study, in São Paulo city, 10 B"-GWGR patients had a statistically significant increased avidity of the anti-V3 antibodies, from 79 percent ± 33 percent to 85 percent ± 75 percent, versus from 48 percent ± 59 percent to 32 percent ± 17 percent for the 10 B-GPGR subjects (p = 0.02). The T CD4+ cells showed a mean increase of + 0.45 cells/month for the B-GPGR subjects and for B"-GWGR the slope was + 1.24 cells/month (p = 0.06), for 62 and 55 months of follow up, respectively. RNA plasma viral load decreased from 3.98 ± 1.75 to 2.16 ± 1.54 log10 in the B"-GWGR group while B-GPGR patients showed one log10 reduction in viral load from 4.09 ± 0.38 to 3.17 ± 1.47 log10 over time (p = 0.23), with a decreasing slope of 0.0042 ± log10,/month and 0.0080 ± log10/month, for B-GPGR and B"-GWGR patients, respectively (p = 0.53). Neither group presented any AIDS defining events during the study, according to Center for Diseases Control criteria. Although the sample size is small, these results may indicate that differences in the pathogenicity of the 2 HIV-1 B serotypes which co-circulate in Brazil may be correlated to the avidity of anti-V3 antibodies.