Victoria Jiménez

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.

High rate of proV47A selection in HIV-2 patients failing lopinavir-based HAART.

We describe the emergence of the proV47A mutation in three out of five HIV-2-infected individuals failing lopinavir/ritonavir-based HAART. The appearance of such mutated variants resulted in high levels of phenotypic resistance to lopinavir, cross-resistance to indinavir, amprenavir, and hypersusceptibility to saquinavir. A search in HIV-2 databases revealed that proV47A is present in 8.6% of protease inhibitor (PI)-experienced patients but absent in all PI-naive patients. Its selection may be a common mutational pathway for developing resistance to lopinavir/ritonavir in HIV-2.

Viral Response to Antiretroviral Therapy in a Patient Coinfected with HIV Type 1 and Type 2

Clinical experience with the treatment of human immunodeficiency virus (HIV) type 2 (HIV-2) infection is limited, and even more scarce is information on therapy for patients coinfected with HIV type 1 (HIV-1) and HIV-2. Here, we describe the outcome for a coinfected patient in whom infection with both viruses was successfully controlled at the start of antiretroviral therapy, but for whom HIV-2 infection escaped control after a treatment simplification change while HIV-1 remained undetectable.

Prevalencia de infección por virus de transmisión parenteral en consumidores actuales de heroína de 3 ciudades españolas

Fundamento y objetivo Determinar la prevalencia de infeccion por el virus de la inmunodeficiencia humana (VIH), virus de la hepatitis B (VHB), hepatitis C (VHC) y virus linfotropico humano de celulas T (HTLV) en consumidores actuales de heroina Sujetos y metodo Estudio transversal sobre 440 heroinomanos de Barcelona, Madrid y Sevilla, en los que se investigo la presencia de anticuerpos frente al VIH, VHC, VHB y HTLV Resultados La prevalencia global de anticuerpos anti-VIH fue del 20% (intervalo de confianza [IC] del 95%, 16,3–23,7%); anti-VHB, 21,4% (IC del 95%, 17,5–25,2%); anti-VHC, 59,1% (IC del 95%, 54,5–63,7%), y anti-HTLV (todos HTLV-II positivos), 3,4% (IC del 95%, 1,7–5,1%). En Barcelona y Madrid encontramos un porcentaje similar de infeccion para cada virus; sin embargo, en Sevilla las prevalencias fueron menores, en especial para el VHC (Barcelona: 59,7% [IC del 95%, 53,1–66,3%]; Madrid: 63,8% [IC del 95%, 56,7–70,9%], y Sevilla: 41,8% [IC del 95%, 28,8–54,9%]) Conclusiones La infeccion por el VHC fue la mas prevalente, y mayor en Barcelona y Madrid que en Sevilla, probablemente por la menor utilizacion en esta ciudad de la via parenteral

Seroreversion of HIV antibodies in patients with prolonged suppression of viraemia under HAART.

Prolonged virus suppression in chronically HIV-infected patients could hypothetically lead to antibody seroreversion. Eighty-four HIV-positive individuals with undetectable viraemia for longer than 5 years under HAART were examined. Only one individual, who had initiated HAART shortly after primary HIV infection, showed seroreversion. In contrast, the cure of hepatitis C virus (HCV) with interferon in 25 controls led to the loss of HCV antibodies in most cases. This information indirectly reflects that whereas HCV may be eradicable HIV is not.

Influence of Human T Cell Lymphotropic Virus Type 2 Coinfection on Virological and Immunological Parameters in HIV Type 1–Infected Patients

BACKGROUNDnHuman 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.nnnMETHODSnImmunological 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.nnnRESULTSnLower 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.nnnCONCLUSIONSnHTLV-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?

ABSTRACT A total of 175 human immunodeficiency virus (HIV)-positive intravenous drug users (IDU) with CD4 cell counts of <200 cells/μl were matched with 175 HIV-positive IDU with CD4 cell counts of >500 cells/μl. 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/μl. 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.

Molecular Characterization of Human T Cell Leukemia Virus Type 1 Subtypes in a Group of Infected Individuals Diagnosed in Portugal and Spain

Over the past decade, Portugal and Spain received large numbers of immigrants from HTLV-1 endemic areas. Our aim was to investigate the diversity of subtypes circulating in these two countries and the introduction of new variants. We performed a molecular analysis of HTLV-1 strains in patients diagnosed since 1998. LTR and env proviral sequences from 26 individuals were analyzed to generate phylogenetic trees along with reference HTLV-1 subtypes from several geographic origins. Epidemiological and clinical data were recorded. Most subjects were immigrants (57.7%) from South America and Africa. All isolates belonged to the cosmopolitan A subtype. Most carried the transcontinental subgroup A, but five subjects carried subgroup D and one carried subgroup C, previously unreported in Europe. HTLV strains showed separate clusters linked to the patients geographic origin. Although subjects with HTLV-1 infection tend not to be engaged in high-risk practices, silent dissemination of a broad diversity of HTLV-1 viruses may still occur.