Influence of human T cell lymphotropic virus type 2 coinfection on virological and immunological parameters in HIV type 1-infected patients.

BACKGROUND: Human T cell lymphotropic virus type 2 (HTLV-2) infection is not rare among injection drug users with human immunodeficiency virus (HIV) infection and may exert a protective role in the progression of HIV disease. METHODS: Immunological and virological parameters were compared in HIV-HTLV-2-coinfected patients and a control group of HIV-monoinfected subjects. All individuals were antiretroviral therapy naive. HIV-specific CD8+ T cell levels were measured using an interferon-gamma assay in response to 125 optimally defined HIV peptides divided into 5 pools. Immune activation was evaluated by measuring levels of CD38 in different CD4+ and CD8+ T cell subsets. In a subgroup of patients, the production of CCL4 in parallel with interferon-gamma was assessed in response to Gag peptides. RESULTS: Lower plasma HIV-RNA levels were found in HIV-HTLV-2-coinfected patients than in HIV-monoinfected patients, despite the 2 groups having similar CD4+ T cell counts. Coinfected patients also had significantly lower levels of CD38 expression in total CD8+ T cells and in its naive subset. CD8+ T cell levels specific for each pool of peptides were similar in both groups, but cells mainly contributing to HIV Gag-specific responses in coinfected patients were CCL4 positive and interferon-gamma negative, whereas for HIV-monoinfected subjects, the response was dominated by CCL4-positive and interferon-gamma-positive cells. CONCLUSIONS: HTLV-2 coinfection may exert a protective role on HIV disease progression by lowering HIV replication and immune activation. A predominance of CCL4 single positive HIV-specific CD8+ T cells in HIV-HTLV-2-coinfected patients could explain this effect.

Can the level of immunosuppression in human immunodeficiency virus-infected patients affect the reliability of human T-cell lymphotropic virus type 2 serological diagnosis?

A total of 175 human immunodeficiency virus (HIV)-positive intravenous drug users (IDU) with CD4 cell counts of <200 cells/microl were matched with 175 HIV-positive IDU with CD4 cell counts of >500 cells/microl. Enzyme immunoassay (EIA) reactivity and human T-cell lymphotropic virus type 2 (HTLV-2) Western blot (WB) positivity were more frequently observed in subjects with CD4 cell counts of >500 cells/microl. Most of the subjects with low CD4 cell counts and EIA reactivity carried HTLV-2 infection (WB positive and/or PCR positive). No subjects with low CD4 cell counts and a lack of reactive EIA were PCR positive for HTLV-2. Therefore, a negative EIA result can confidently discharge HTLV-2 infection in HIV-infected patients with severe immunosuppression, whereas PCR should be performed for subjects with a reactive HTLV EIA which is not further confirmed by WB.

Infection with human T lymphotropic virus type I in organ transplant donors and recipients in Spain.

Human T-cell lymphotropic virus (HTLV) antibody screening is not recommended uniformly before transplantation in Western countries. In the year 2001, the first cases of HTLV-I infection acquired through organ transplantation from one asymptomatic carrier were reported in Europe. All three organ recipients developed a subacute myelopathy shortly after transplantation. This report rose the question about whether to implement universal anti-HTLV screening of all organ donors or selective screening of donors from endemic areas for HTLV-I infection should be carried out. A national survey was conducted thereafter in which anti-HTLV antibodies were tested in 1,298 organ transplant donors and 493 potential recipients. None was seropositive for HTLV-I and only one recipient, a former intravenous (i.v.) drug user, was found to be infected with HTLV-II. In a different survey, HTLV screening was conducted in 1,079 immigrants and 5 (0.5%) were found to be asymptomatic HTLV-I carriers. All came from endemic areas for HTLV-I infection. No cases of HTLV-II infection were found among immigrants. These results support the current policy of mandatory testing of anti-HTLV antibodies in Spain only among organ transplant donors coming from HTLV-I endemic areas or with a highly suspicion of HTLV-I infection.

Molecular epidemiology of HTLV-2 infection among intravenous drug users in Spain.

BACKGROUND: HTLV-2 infection is prevalent among intravenous drug users (IDUs), which often are coinfected with HIV-1. Two main subtypes, HTLV-2a and -2b, have been described among European IDUs, with a characteristically geographic distribution: IIa in northern Europe and IIb in the south. Although frequent traveling within Europe might have favoured a wide dissemination of diverse HTLV-2 variants, HTLV-2b was so far the only subtype reported in Spain. OBJECTIVE: To investigate the current molecular epidemiology of HTLV-2 in Spain. STUDY DESIGN: Twenty-six new HTLV-2 strains isolated from IDUs over the last 11 years in different geographic regions were examined. The HTLV LTR region (620bp) was sequenced and phylogenetic analyses were performed. Endonuclease restriction sites were examined to further characterize the HTLV-2 subgroup. RESULTS: All 26 individuals infected with HTLV-2 showed viruses belonging to the HTLV-2 b4 clade and were closely related to the previously reported HTLV-2 Spanish and Italian IDU isolates. CONCLUSIONS: HTLV-2 subtype b4 continues to be the only HTLV-2 subgroup recognized so far in Spain and no introduction of other HTLV-2 variants has occurred over the last 11 years.

[Rate of infection by blood-borne viruses in active heroin users in 3 Spanish cities]. / Prevalencia de infección por virus de transmisión parenteral en consumidores actuales de heroína de 3 ciudades españolas.

BACKGROUND AND OBJECTIVE: The objective of this paper was to determine the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) and human T lymphotropic virus (HTLV) infections in active heroin users in Spain. SUBJECTS AND METHOD: A cross-sectional study was carried out in 440 heroin users in three different urban areas of Spain: Barcelona, Madrid, and Seville. Specimens were analyzed for the presence of anti-HIV, anti-HCV, anti-HBc, and anti-HTLV antibodies. RESULTS: The rate of anti-HIV antibodies was 20% (CI 95%, 16.3-23.7%); anti-HBc: 21.4% (CI 95%, 17.5-25.2%); anti-HCV: 59.1% (CI 95%, 54.5-63.7%); and anti-HTLV (HTLV-II in all cases): 3.4% (CI 95%, 1.7-5.1%). Barcelona and Madrid had similar rates for each virus, yet these were lower in Seville especially with regard to HCV (Barcelona: 59.7% [CI 95%, 53.1-66.3%]; Madrid: 63.8% [CI 95%, 56.7-70.9%]; Seville: 41.8% [CI 95%, 28.8-54.9%]). CONCLUSIONS: HCV is the most prevalent infection among active heroin users in Spain. The rate of infection by blood-borne viruses is higher in Madrid and Barcelona than in Seville (notably for HCV), most likely due to a lower rate of intravenous users in this city.

Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection.

BACKGROUND: It is unclear whether resistance to immunologic damage in long-term non-progressors (LTNP) will last indefinitely or whether it merely represents the extreme of a Gaussian distribution, and therefore progression will occur eventually. PATIENTS AND METHODS: A cohort of 19 LTNP was established in 1997. Plasma viraemia and CD4 cell counts were measured two to three times each year until 2003. Analyses of nef and vpr viral genes, CCR5 genotypes, co-receptor tropism, viral replication capacity, and immunological parameters were performed. RESULTS: Twelve subjects (non-progressors, NP) showed stable CD4 cell counts over the 6-year follow-up, while seven (slow progressors, SP) showed a trend towards progressive CD4 cell depletion; however, only three SP experienced significant CD4 cell count declines. All SP had detectable plasma HIV-RNA (median 1118 copies/ml). In contrast, five of 12 NP had always undetectable viraemia. Only one patient showed a deletion in nef. The vpr R77Q change was recognized in seven patients. All patients were infected with R5 viruses. The virus replicative capacity was reduced in all tested individuals (range 5-93%). None of the patients was homozygous for the delta-32 CCR5 genotype, which was found in heterozygosis in three. CD8 T-cell activation was low in all but three individuals, all of whom had detectable viraemia and showed progressive CD4 cell depletion. Cytotoxic T lymphocyte responses were similar to those found in a control group of HIV progressors. CONCLUSIONS: A substantial proportion of LTNP show low-level virus replication and progressive loss of CD4 T cells over time. Progressive immunologic damage seems to be directly associated with some degree of virus replication and T-cell activation.

[HIV-2 and HTLV-I/II infections in Spain]. / Infecciones por VIH-2 y HTLV-I/II en España.

Up to December 2002, a total of 56, 566 and 109 cases of human T-lymphotropic virus type 1 (HTLV-I), HTLV-II and human immunodeficiency virus type 2 (HIV-2) infection, respectively, were identified in Spain. Most HTLV-I- and HIV-2-infected subjects were immigrants from endemic areas or Spaniards who had traveled to, or had sexual contacts with natives from, these areas. In contrast, HTLV-II infection was mainly limited to Spanish intravenous drug users (IDU) who were frequently coinfected with HIV-1. Among HTLV-I-infected patients, 12 developed subacute myelopathy and 4 adult T-cell leukemia. As for the HIV-2-positive subjects, only 20 (18.3%) developed AIDS. There was no evidence of an increase in the incidence of HIV-2 and HTLV-I infections over time. In contrast, HTLV-II infection has spread in recent years among the HIV-1-positive IDU population in prisons, with a rate of 18% in some regions of Spain. Nevertheless, the prevalence of HTLV-II infection in HIV-1-positive IDU outpatients is still low (4.7%).