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1.
Scand J Immunol ; 82(1): 55-62, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25833795

RESUMO

To study vitamin D (25OH D3 ) in relation to (i) microbial translocation (ii) systemic inflammation and (iii) blood lipid markers, in Caucasian, well-controlled HIV patients and healthy controls, plasma and serum samples from n = 97 male, HIV patients on HAART with immeasurable viral load (<20 copies/ml) since median 6.5 years and no concurrent inflammatory or infectious disease and n = 30 healthy controls were analysed for (i) LPS; (ii) sCD14, hsCRP, IL-4, IL-6, IL-10, IL-17, MCP-1 and IFN-γ; as well as (iii) blood lipids. Vitamin D levels were similarly distributed and equally low in both HIV patients and controls. There was no association between vitamin D levels and markers of microbial translocation, systemic inflammation or dyslipidemia. LPS levels were similar in both groups but HIV patients expressed higher levels of sCD14 and hsCRP, with HIV as an independent risk factor. HIV patients had higher cholesterol and Apo B levels. Notably, more HIV patients smoked and smoking was associated with lower vitamin D levels. In conclusion; these well-treated Caucasian HIV patients had similar vitamin D levels as healthy controls. However, despite perfect virological control, they exhibited slightly increased inflammatory markers and disturbed blood lipids. However, neither of these parameters were associated with low vitamin D levels but appeared to be linked to the HIV-disease per se. Thus, the rationale for vitamin D substitution as a way to improve microbial translocation and systemic inflammation is not fully supported in this HIV population.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Vitamina D/sangue , Adulto , Apolipoproteínas B/sangue , Biomarcadores/sangue , Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Citocinas/sangue , Dislipidemias/sangue , Humanos , Inflamação/sangue , Inflamação/imunologia , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Suécia , Carga Viral
2.
Int J STD AIDS ; 23(6): 455-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22807547

RESUMO

We report two instances of urethral-to-rectal transmission of Mycoplasma genitalium (MG) in men who have sex with men (MSM) couples. Such clear epidemiological correlation has to our knowledge not been published before. The urethral infections led to clinical symptoms, but the rectal infections did not. The rectum might serve as a reservoir for MG in MSM, but there is also some evidence from the literature that MG can cause proctitis. Our finding raises important questions about the role of MG as a pathogen among MSM. Any correlation with HIV transmission risk is currently unknown and needs further research.


Assuntos
Homossexualidade Masculina , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/transmissão , Mycoplasma genitalium/isolamento & purificação , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/transmissão , Humanos , Masculino , Doenças Retais/microbiologia , Comportamento Sexual , Doenças Uretrais/microbiologia
3.
AIDS Care ; 18(4): 407-14, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16809121

RESUMO

The purposes of the study were to measure adherence with antiretroviral therapy to dose, schedule, and dietary instructions in a sample of patients with HIV infection in Stockholm, Sweden, over a 2-year period and identify baseline predictors of the three types of adherence. The study cohort consists of 144 patients who completed at least six out of seven follow-up self-reported adherence questionnaires. Baseline self-administrated questionnaire examined socio-demographics, medication-related, psychological, cognitive, and social context factors and self-reported adherence. Biomedical data were obtained through patients' medical records. Summary dose, schedule, and dietary instructions adherence scores provided outcome measures reflecting 100% adherence across all time points or not 100% adherence during at least one measurement period. A total of 61% maintained consistent full-dose adherence throughout baseline and all follow-up visits and equivalent proportion of 100% schedule adherence was 39%. Among patients with dietary instructions, 37% retained consistent adherence at all visits. Only schedule adherence was predicted by baseline data; perceived pressures from medical staff to take HIV medications (OR 0.51, p < .05), life stress (OR 0.13, p < .01), ART health concerns (OR 0.19, p < .01), and ART prolongs one's life (OR 0.39, p < .05) predicted reduced schedule adherence over time. Perceived medication pressures from those close to the patient (OR 1.76, p < .05), post-traumatic stress disorder symptoms (OR 1.07 p<.01), and adherence self-efficacy (OR 3.50, p < .05) predicted positive schedule adherence over time. These results clearly illustrate difficulties in sustaining ART adherent behaviour, in particular schedule and dietary restrictions, over time and thus emphasizes the importance of multiple periodic assessments of all three types of adherence. Interventions aimed at improving schedule adherence should in particular focus on psychological and cognitive factors.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Adulto , Idoso , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Suécia
4.
AIDS Care ; 18(3): 246-53, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16546786

RESUMO

The purposes of the study were to measure adherence with antiretroviral therapy to dose, schedule, and dietary instructions in a sample of patients with HIV infection in Stockholm, Sweden, over a 2-year period and identify baseline predictors of the three types of adherence. The study cohort consists of 144 patients who completed at least six out of seven follow-up self-reported adherence questionnaires. Baseline self-administrated questionnaire examined socio-demographics, medication-related, psychological, cognitive, and social context factors and self-reported adherence. Biomedical data were obtained through patients' medical records. Summary dose, schedule, and dietary instructions adherence scores provided outcome measures reflecting 100% adherence across all time points or not 100% adherence during at least one measurement period. A total of 61% maintained consistent full-dose adherence throughout baseline and all follow-up visits and equivalent proportion of 100% schedule adherence was 39%. Among patients with dietary instructions, 37% retained consistent adherence at all visits. Only schedule adherence was predicted by baseline data; perceived pressures from those close to the patient to take HIV medications (OR 0.51, p<.05), life stress (OR 0.13, p 0.009), ART health concerns (OR 0.19, p 0.003), and ART prolongs one's life (OR 0.39, p 0.04) predicted reduced schedule adherence over time. Perceived medication pressures from medical staff (OR 1.76, p<.05), post-traumatic stress disorder symptoms (OR 1.07 p<.01), and adherence self-efficacy (OR 3.50, p<.05) predicted positive schedule adherence over time. These results clearly illustrate difficulties in sustaining ART adherent behaviour, in particular schedule and dietary restrictions, over time and thus emphasizes the importance of multiple periodic assessments of all three types of adherence. Interventions aimed at improving schedule adherence should in particular focus on psychological and cognitive factors.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Adulto , Idoso , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Suécia
5.
AIDS Res Hum Retroviruses ; 20(8): 860-70, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15320990

RESUMO

The aim of this study was to evaluate the immunological responses induced by DNA plasmids containing HIV regulatory genes administered in combination in HIV-1-infected patients with pretreatment with highly active antiretroviral treatment (HAART). The study is a double-blind, randomized, and placebo-controlled study, including 15 asymptomatic HIV-1-infected patients on stable HAART for at least 6 months and with plasma HIV RNA levels below 50 copies/ml. Ten patients received a combination of rev, tat, and nef intramuscularly (im) at weeks 0, 4, and 16 at increasing doses giving totals of 300 (100 x 3), 900 (300 x 3), and 1800 (600 x 3) micrograms DNA. Five patients received saline in the same amounts im. Antigen-specific cytotoxic T lymphocyte (CTL) levels were preserved or increased and new T lymphocyte proliferative responses were induced in the group immunized with the HIV DNA genes. No increase in antibody levels was noted. Despite a 10-fold higher vaccine dose, patients on HAART did not respond better to vaccination compared to non-HAART patients included in a previous study where the genes were administered separately. Combining the regulatory genes rev, tat, and nef in increasing doses may reduce the anticipated augmentation of HIV-specific T cell proliferative and CTL responses. Viral suppression did not seem to further improve the initial vaccine responses of patients with comparable CD4 levels.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/imunologia , Infecções por HIV/terapia , HIV-1 , Vacinas de DNA/imunologia , Vacinas contra a AIDS/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antígenos Virais/biossíntese , Terapia Antirretroviral de Alta Atividade , Método Duplo-Cego , Genes Virais , HIV-1/genética , HIV-1/imunologia , Humanos , Vacinas de DNA/administração & dosagem , Carga Viral
6.
HIV Med ; 4(2): 101-10, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12702130

RESUMO

OBJECTIVE: To study the impact of effective highly active antiretroviral therapy (HAART) on the preservation of long-term CD4 memory cells induced by vaccines in HIV-1-infected patients. METHODS: Thirty HIV-1-positive patients on HAART with undetectable viral load were randomized into three groups: 10 received HIV-1 rgp160 vaccine, 10 received tetanus vaccine and 10 patients were not immunized. As controls, 10 HIV-negative volunteers were immunized with tetanus vaccine. The results were compared with an rgp160 vaccine study performed before the era of HAART on patients with comparable CD4 levels. All patients were monitored for 2 years for T-cell proliferative responses, T-cell subset levels, serum IgG and viral load. RESULTS: After 1 year all patients immunized with rgp160 had strong T-cell responses to the rgp160 antigen. After 2 years this response was preserved in the HAART-treated group, but not in the rgp160 immunized non-HAART group, despite comparable CD4 levels. Recall effects of the CD4-specific responses towards other antigens were seen in the rgp160-immunized HAART group. CONCLUSION: Immunization with rpg 160 leads to positive effects on HIV-specific T-cell proliferative responses in patients both with and without HAART. Immune responses after immunization is better preserved in HAART-treated patients who have low viral amounts than in individuals with high viral load and no HAART despite comparable CD4 levels during 2 years' follow-up. Interruption of HAART with return of a high viral load might thus have negative effects on T-cell functions in the long term, even if CD4 levels are kept at clinically acceptable levels.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Infecções por HIV/imunologia , Infecções por HIV/terapia , HIV-1 , Adulto , Anticorpos Antivirais/sangue , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Terapia Combinada , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Seguimentos , HIV-1/genética , HIV-1/imunologia , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estatísticas não Paramétricas , Linfócitos T/imunologia , Toxoide Tetânico/administração & dosagem
7.
J Intern Med ; 252(6): 570-4, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12472919

RESUMO

Protease inhibitors used as therapy for HIV-1 infection have been associated with metabolic side-effects such as peripheral fat wasting, central adiposity, hyperlipidaemia and insulin resistance. This metabolic disorder is known as the lipodystrophy syndrome. This syndrome can be recognized by the early appearance of an increase in serum triglyceride, cholesterol and plasma-free fatty acid levels. Here, we describe an HIV-1 positive patient with the lipodystrophy syndrome in whom a decline in serum triglycerides was seen along with a significant improvement in glucose uptake following treatment with bezafibrate for 3 months. This improvement may be a consequence of the Randle effect, i.e. increased availability of plasma-free fatty acids is negatively correlated to glucose uptake. We also noted a significant improvement in endothelial-dependent flow-mediated dilatation after treatment with bezafibrate. This effect could result from the increased glucose uptake observed and a decrease in insulin resistance secondary to the lowered triglyceride levels by bezafibrate. We conclude that bezafibrate may be of clinical utility in the lipodystrophy syndrome, through its beneficial effects on insulin resistance, glucose uptake and endothelial dysfunction.


Assuntos
Bezafibrato/uso terapêutico , Glicemia/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Resistência à Insulina/fisiologia , Adulto , Artéria Braquial/efeitos dos fármacos , Endotélio Vascular , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Humanos , Masculino , Vasodilatação/efeitos dos fármacos
8.
Vaccine ; 20(15): 1988-93, 2002 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-11983260

RESUMO

Clinical and experimental studies of HIV-1 subcomponents were made in order to increase their immunogenicity. HIV subtype envelopes A, B and C have been compared and a detailed analysis made by peptides of the coreceptor-ligand interactions. We identified a direct interaction between HIV-1 envelope and a cellular receptor at the amino acid level. Both the viral subtype and its tropism appeared to influence inhibition of infection. Genetic immunization induced new cytotoxic responses while proteins appeared to efficiently boost previous responses. One HIV-1 subtype B antigen was strongly immunogenic in a human immunotherapeutic trial and permitted better survival at 2 years of the study in patients with poor prognosis.


Assuntos
Vacinas contra a AIDS/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp160 do Envelope de HIV/imunologia , HIV-1/classificação , Fragmentos de Peptídeos/metabolismo , Receptores CXCR4/metabolismo , Transferência Adotiva , Sequência de Aminoácidos , Animais , Apresentação de Antígeno , Ensaios Clínicos como Assunto , Reações Cruzadas , Método Duplo-Cego , Genes env , Anticorpos Anti-HIV/biossíntese , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/genética , HIV-1/imunologia , Humanos , Imunidade Celular , Vírus da Leucemia Murina/genética , Vírus da Leucemia Murina/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Estudos Prospectivos , Ligação Proteica , Estrutura Terciária de Proteína , Vírus Reordenados/imunologia , Receptores CXCR4/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Relação Estrutura-Atividade , Subpopulações de Linfócitos T/imunologia , Vacinação
9.
AIDS Res Hum Retroviruses ; 17(4): 277-86, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11242515

RESUMO

Both naive and memory T lymphocyte responses are lost during advanced HIV infection. Treatment with highly active antiretroviral therapy (HAART) is associated with an increase in T lymphocytes and a reduction in viral load. However, the viral response to HAART in patients with low levels of helper T lymphocytes and a high viral load is often not satisfactory. We investigated the capacity of long-term HAART to reconstitute the immune system in severely ill patients. A nonselected longitudinal patient population with high baseline viral levels and CD4(+) cells below 100 x 10(6)/liter were monitored for 2 years during HAART. Markers to estimate the therapeutic effects included viral levels and cell surface markers representing naive and memory T lymphocytes as well as activation markers, B cells, NK cells, and clinical events. After 2 years of treatment, viral load was reduced to undetectable levels in 55% (viral responders, vRs) and less than 1 log (median value) from baseline in 45% (viral low responders, vLRs). Elevated numbers of memory and naive CD4(+) and CD8(+) cells as well as a decrease in activation markers were seen in both vRs and vLRs. However, the magnitude was greater in vRs. No differences in the clinical outcome were observed between vRs and vLRs. We conclude that most patients, even in advanced stages of HIV disease, benefited from HAART. The magnitude of the response was related to good viral reduction, but even patients with poor viral reduction had a recovery of naive and memory CD4(+) and CD8(+) cells. Even a small reduction in viral load is thus of importance for health and potentially also for years of survival.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/fisiologia , RNA Viral/sangue , Adulto , Linfócitos B/imunologia , Feminino , Citometria de Fluxo , Infecções por HIV/virologia , Humanos , Memória Imunológica , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento , Carga Viral
10.
JAMA ; 284(14): 1806-13, 2000 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-11025833

RESUMO

CONTEXT: Numerous studies have demonstrated that hearing aids provide significant benefit for a wide range of sensorineural hearing loss, but no carefully controlled, multicenter clinical trials comparing hearing aid efficacy have been conducted. OBJECTIVE: To compare the benefits provided to patients with sensorineural hearing loss by 3 commonly used hearing aid circuits. DESIGN: Double-blind, 3-period, 3-treatment crossover trial conducted from May 1996 to February 1998. SETTING: Eight audiology laboratories at Department of Veterans Affairs medical centers across the United States. PATIENTS: A sample of 360 patients with bilateral sensorineural hearing loss (mean age, 67.2 years; 57% male; 78.6% white). INTERVENTION: Patients were randomly assigned to 1 of 6 sequences of linear peak clipper (PC), compression limiter (CL), and wide dynamic range compressor (WDRC) hearing aid circuits. All patients wore each of the 3 hearing aids, which were installed in identical casements, for 3 months. MAIN OUTCOME MEASURES: Results of tests of speech recognition, sound quality, and subjective hearing aid benefit, administered at baseline and after each 3-month intervention with and without a hearing aid. At the end of the experiment, patients ranked the 3 hearing aid circuits. RESULTS: Each circuit markedly improved speech recognition, with greater improvement observed for soft and conversationally loud speech (all 52-dB and 62-dB conditions, P

Assuntos
Auxiliares de Audição , Perda Auditiva Neurossensorial/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Percepção Auditiva , Estudos Cross-Over , Método Duplo-Cego , Feminino , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente
11.
Int J STD AIDS ; 11(7): 451-5, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10919487

RESUMO

The long-term effects of fat metabolism, storage and utilization in HIV-1 infected patients on highly active antiretroviral therapy (HAART) including a protease inhibitor are profound and cause increasing concern. The main importance of these lipid/metabolic disorders lies in their assumed contribution to an increased risk of coronary heart disease (CHD). In the general population increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor for CHD by itself as well as in combination with increased levels of cholesterol and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1 positive patients were screened for cardiovascular risk factors. The subjective perception of fat wasting and/or accumulation in different sites of the body, which was possible to evaluate in 235 patients on HAART and 73 treatment-naive patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high-density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of the patients on HAART, 42% (98/235) reported abnormal fat distribution as compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a) levels (> 700 mg/l) were more common among HAART patients as compared with naive, 14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not differ between patients with and without subjective perception of abnormal fat distribution. A significant number of the HAART patients had very high levels of Lp(a) and various combinations of increased lipid values associated with considerably increased risk for CHD. The elevation of Lp(a) did not relate to any other clinical or laboratory parameter than to LDL-cholesterol.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doenças Cardiovasculares/etiologia , Infecções por HIV/tratamento farmacológico , HIV-1 , Lipídeos/sangue , Adulto , Doenças Cardiovasculares/complicações , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Masculino , Fatores de Risco , Triglicerídeos/sangue
12.
J Virol ; 74(10): 4888-90, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10775629

RESUMO

Immunization with a recombinant glycoprotein 160 envelope immunogen derived from a virus of genetic subtype B induced strong specific T-helper cell responses in asymptomatic human immunodeficiency virus (HIV) carriers infected with subtypes B to G. This indicates that the HIV-specific T-helper immunity, which is the basis for development of antibodies and cytotoxic T lymphocytes, can be improved by both homologous and heterologous antigens. It also suggests that a particular immunogen can be effective against many different HIV strains.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas contra a AIDS/administração & dosagem , Reações Cruzadas , Proteína gp160 do Envelope de HIV/administração & dosagem , Proteína gp160 do Envelope de HIV/genética , Proteína gp160 do Envelope de HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , Humanos , Ativação Linfocitária , Vacinação , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
13.
Intervirology ; 43(4-6): 294-301, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11251385

RESUMO

OBJECTIVES: We evaluated whether DNA immunization with HIV-1 regulatory genes change natural killer (NK) effector cell activity. NK cells are the most important cells for the immediate host defense against virus-infected and tumor cells. We analyzed the NK activities of HIV-1-infected individuals against K562 cells (the classical assay) as well as against a CD4+ cell line with and without HIV-1 infection. CD4+ T lymphocytes are the main target cells for HIV-1 infection in vivo. Various proportions of the CD4+ T lymphocyte population carry the HIV-1 genome, produce virus and contribute to the systemic spread of HIV-1. METHODS: CD4+ cell lines were established through HTLV-1 transformation which made the cells susceptible to NK lysis. NK activity was then tested in a (51)Cr release assay. RESULTS: NK cells of asymptomatic HIV-infected individuals mediated considerable lytic activity against K562 cells as well as against the uninfected and HIV-1-infected CD4+ cell line, and so did the NK cells of HIV-1-infected patients on highly active antiretroviral treatment. CONCLUSION: DNA immunization with HIV-1-regulatory genes did not significantly change the NK effector cell activity.


Assuntos
Vacinas contra a AIDS/imunologia , Genes Reguladores/imunologia , Infecções por HIV/imunologia , Células Matadoras Naturais/imunologia , Vacinação , Vacinas de DNA/imunologia , Vacinas contra a AIDS/genética , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular Transformada , Infecções por HIV/tratamento farmacológico , HIV-1/genética , HIV-1/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos
15.
Int J STD AIDS ; 10(8): 514-21, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10471100

RESUMO

Forty asymptomatic HIV-infected individuals with CD4+ lymphocyte levels above 400x10(6)/l were immunized over 5 years with recombinant envelope glycoprotein gp160 (rgp160). After 5 years there was a trend towards more non-progressors in the immunized group as compared to the matched controls. Since immunizations could activate HIV, the first 6 immunizations were followed by 2 weeks of zidovudine or placebo, double-blind. The viral load did not change during the first 6 months and was not different from that of the matched controls after 5 years. The best effect on CD4+ lymphocyte development was seen in individuals with a high viral load randomized to rgp160+zidovudine and in individuals with a low viral load randomized to rgp160+placebo. We conclude that rgp160 is safe and results in temporarily improved CD4+ development. Concomitant antiviral treatment might be of benefit, especially in patients with a more advanced disease and can today be given with more effective combinations.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Proteína gp160 do Envelope de HIV/uso terapêutico , Soropositividade para HIV/terapia , HIV-1/imunologia , Imunoterapia , Vacinas Sintéticas/uso terapêutico , Zidovudina/uso terapêutico , Vacinas contra a AIDS/efeitos adversos , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Combinada , Interpretação Estatística de Dados , Método Duplo-Cego , Feminino , Proteína gp160 do Envelope de HIV/efeitos adversos , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , Humanos , Imunoterapia/efeitos adversos , Masculino , Fatores de Tempo , Vacinas Sintéticas/efeitos adversos , Zidovudina/efeitos adversos
16.
J Immunol ; 163(4): 2330-8, 1999 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10438897

RESUMO

Intensive chemotherapy is capable of reducing the viral load in HIV-1-infected individuals while infected cells are still present. A special property of DNA immunization is to induce both new CTL and Ab responses. We evaluated the possibility of inducing new immune responses in already infected individuals by means of DNA constructs encoding the nef, rev, or tat regulatory HIV-1 genes. Significant changes in viral loads and CD4+ counts were observed in four patients who started highly active antiretroviral treatment (HAART) during the immunization study. The DNA immunization induced Ag-specific T cell proliferation, which persisted up to 9 mo after the last DNA injection, and cytolytic activities but did not, by itself, reduce viral load. Increased levels of CTL precursor cells were induced in all nine DNA-immunized patients. The profile of IFN-gamma secretion observed when human PBMC were transfected with the nef, rev, and tat DNA resembled that found in the CTL activity (nef > tat > rev). Ab responses that occurred after immunizations were of a low magnitude. In accordance with the high IL-6 production induced by the nef DNA plasmid, IgG titers were highest in patients immunized with nef DNA. The initiation of HAART appears to contribute to the induction of new HIV-specific CTL responses, but by itself did not cause obvious re-induction of these activities.


Assuntos
Vacinas contra a AIDS/imunologia , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/imunologia , Infecções por HIV/terapia , HIV-1/imunologia , Vacinas de DNA/imunologia , Anticorpos Antivirais/biossíntese , Antígenos Virais/biossíntese , Contagem de Linfócito CD4/efeitos dos fármacos , Terapia Combinada , Citocinas/biossíntese , Testes Imunológicos de Citotoxicidade , Quimioterapia Combinada , Epitopos de Linfócito T/análise , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , HIV-1/efeitos dos fármacos , Humanos , Estudos Longitudinais , Ativação Linfocitária/efeitos dos fármacos , Contagem de Linfócitos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/imunologia , Células-Tronco/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Carga Viral
17.
AIDS ; 13(9): 1071-5, 1999 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-10397537

RESUMO

BACKGROUND: The two widely spread human polyomaviruses, BK virus (BKV) and JC virus (JCV) establish latency in the urinary tract, and can be reactivated in AIDS. JCV might cause progressive multifocal leucoencephalopathy, but although up to 60% of AIDS patients excrete BKV in the urine there have been few reports of BKV-related renal and/or neurological disease in AIDS. OBJECTIVE: To report on an AIDS patient with progressive renal and neurological symptoms involving the retina. DESIGN: Case report. SETTING: Venhälsan, Söder Hospital, Stockholm, Sweden. METHODS: The brain, eye tissue, cerebrospinal fluid, urine and peripheral blood mononuclear cells were analysed by nested PCR for polyoma-virus DNA. Macroscopical and microscopical examination were performed of the kidney and brain post mortem. Immunohistochemical stainings for the two BKV proteins, the VP1 and the agnoprotein, were performed on autopsy material and virus infected tissue culture cells. RESULTS: BKV could be demonstrated in the brain, cerebrospinal fluid, eye tissues, kidneys and peripheral blood mononuclear cells. CONCLUSION: During 6 years, approximately 400 cerebrospinal fluid samples from immunosuppressed individuals with neurological symptoms have been investigated by PCR for the presence of polyomaviruses. BKV DNA has, so far, only been found in the case reported here. Although reports of BKV infections in the nervous system are rare, there is now evidence for its occurrence in immunocompromised patients and the diagnosis should be considered in such patients with neurological symptoms and signs of renal disease. The diagnosis is simple to verify and is important to establish.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Vírus BK/isolamento & purificação , Encefalite Viral/virologia , Nefrite/virologia , Infecções por Papillomavirus/diagnóstico , Retinite/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Animais , Vírus BK/genética , Encéfalo/patologia , Encéfalo/virologia , DNA Viral/análise , Encefalite Viral/patologia , Humanos , Imuno-Histoquímica , Rim/patologia , Rim/virologia , Masculino , Nefrite/patologia , Infecções por Papillomavirus/virologia , Ratos , Infecções Tumorais por Vírus/virologia , Proteínas Virais/análise , Proteínas Virais Reguladoras e Acessórias
18.
Ophthalmology ; 106(1): 129-32, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9917793

RESUMO

OBJECTIVE: To report the clinical and histopathologic characteristics of BK virus (BKV) retinitis. DESIGN: Case report. TESTING: The clinical features of bilateral retinitis in a 29-year-old homosexual white male with the acquired immune deficiency syndrome (AIDS) included focal, mottled fundus pigmentation, and haloes, as documented by fundus photography. After death of the patient, the left eye was studied by light microscopic and immunohistochemical examination. The nested polymerase chain reaction (PCR) was used to detect viral deoxyribonucleic acid (DNA) in the right eye and other nonocular tissues. The specificity was then confirmed by restriction enzyme analysis. RESULTS: The retina of the left eye showed focal necrosis and contained cells with intranuclear staining for the BKV VP1 protein. In the right eye, BKV DNA was detected in the retina and other tissues by nested PCR. Autopsy showed that BKV infection was also present in the brain, kidneys, and peripheral blood mononuclear cells. CONCLUSIONS: A number of pathogens may cause retinitis in patients with AIDS. The authors have shown that BKV should be included among those pathogens and that some clinical features may suggest the presence of BKV retinitis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Vírus BK/genética , Proteínas do Capsídeo , Infecções Oculares Virais/diagnóstico , Infecções por Papillomavirus/diagnóstico , Retinite/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Capsídeo/metabolismo , DNA Viral/análise , Infecções Oculares Virais/metabolismo , Infecções Oculares Virais/virologia , Fundo de Olho , Humanos , Técnicas Imunoenzimáticas , Masculino , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Retinite/metabolismo , Retinite/virologia , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/virologia
19.
AIDS ; 12(16): 2193-202, 1998 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-9833861

RESUMO

BACKGROUND: The efficacy of highly active antiretroviral treatment (HAART) in HIV-1 disease may vary between nucleoside-naive and experienced patients as well as between patients with different viral phenotypes and in different stages of disease. OBJECTIVE: To investigate variables of importance for successful long-term viral suppression by analysing virological, clinical and immunological characteristics at initiation of protease inhibitor treatment on suppression of HIV RNA over 1 year. DESIGN: An open, non-randomized, observational clinical study. SETTING: Venhälsan, Department of Dermatovenereology, Söder Hospital, Stockholm, Sweden. PATIENTS: A total of 147 unselected advanced patients with known HIV-1 infection for a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996. INTERVENTIONS: All patients received HAART with at least two nucleoside analogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analogues for a mean of 39 months. MEASUREMENTS: CD4+ lymphocyte count, plasma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at baseline. Viral load and CD4+ lymphocyte count were determined every 3 months. RESULTS: Patients were analysed on an intention-to-treat basis. The mean CD4+ lymphocyte count at baseline was 170 x 10(6)/l and the median viral load was 68 600 copies/ml. Heterozygosity for the delta32 deletion of the CCR-5 gene (delta32/wt) was found in 27%. MT-2 positive virus (syncytium-inducing) was isolated in 46%. Logistic regression revealed that nucleoside analogue experience and baseline log10 HIV-1 RNA were the only factors independently related to plasma HIV-1 RNA levels below 500 copies/ml after 1 year of treatment, which was found in 69%. CONCLUSION: The virological outcome after 1 year of HAART was strongly correlated to prior treatment history and baseline viral load, whereas CD4+ lymphocyte count, CCR-5 genotype and viral biological phenotype had less influence. The long-term antiviral efficacy of HAART was lowest in individuals with previous nucleoside analogue treatment and a high baseline viral load. In these individuals an even more aggressive treatment should be considered.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Carga Viral , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Infecções por HIV/imunologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Estudos Longitudinais , Masculino , Inibidores de Proteases/uso terapêutico , RNA Viral/sangue , Análise de Regressão , Estatísticas não Paramétricas , Tropismo
20.
Cytometry ; 33(2): 115-22, 1998 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-9773871

RESUMO

Increased activation of CD8+ T cells, particularly increased expression of CD38 antigen, has been shown to strongly correlate with progression of human immunodeficiency virus-positive (HIV+) individuals to acquired immunodeficiency syndrome (AIDS) and death. As part of a study evaluating responses to a recombinant gp160 vaccine, we have used quantitative three-color flow cytometry (QFCM) to further investigate the relationships among several measures of lymphocyte activation/immunological status. Parameters evaluated included 1) absolute circulating counts for the major lymphocyte phenotypes (T, B, NK) and selected activated/regulatory subsets believed to have clinical value in the monitoring of patients with HIV infection; 2) level of CD38 expression (antibody-binding capacity [ABC]) on the lymphocyte subsets defined by CD8, CD38, and HLA-DR; and 3) serum levels of soluble CD8. CD8+DR+CD38+ counts were found to be markedly increased (approximately 10-fold) in HIV+ individuals, whereas CD4+CD45RA+ counts were markedly decreased (approximately 5-fold). We confirmed previous reports that CD38 expression on CD8 T cells (here reported as CD38 ABC) are increased in asymptomatic HIV+ individuals as compared with healthy controls, and further found that CD38 ABC was elevated approximately 2-fold on CD8+DR+ cells as compared with CD8+DR- cells in healthy controls, and almost 2-fold further elevated on CD8+DR+ cells in HIV+ individuals compared with CD8+DR+ cells in healthy controls. In agreement with previous studies, we found increased serum CD8 levels (sCD8) and increased CD8+DR+ counts in asymptomatic HIV+ individuals. However, when sCD8 was expressed relative to CD8+DR+ cell counts (RsCD8), this index was found to be significantly decreased in HIV+ individuals. Although CD38 ABC on CD8+DR+ cells showed no correlation with sCD8, it was significantly correlated with RsCD8 in both HIV+ and HIV- individuals. Absolute lymphocyte counts were strongly correlated with both CD38 ABC and RsCD8 in HIV+ individuals. However, CD4 counts were correlated with CD38 ABC (but not RsCD8) in HIV+ patients and with RsCD8 (but not CD38 ABC) in HIV-controls. Our results suggest that QFCM is significant in understanding the role of CD8+DR+CD38+ cells in processes such as lymphocyte homeostasis and HIV-induced CD4-cell depletion.


Assuntos
Antígenos de Diferenciação/biossíntese , Infecções por HIV/sangue , Ativação Linfocitária , NAD+ Nucleosidase/biossíntese , Subpopulações de Linfócitos T/imunologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Vacinas contra a AIDS , Adulto , Antígenos CD/análise , Antígenos de Diferenciação/análise , Contagem de Linfócito CD4 , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , NAD+ Nucleosidase/análise , Subpopulações de Linfócitos T/metabolismo
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