Assuntos
Síndrome da Imunodeficiência Adquirida/etiologia , Vacina Antipólio de Vírus Inativado , Síndrome da Imunodeficiência Adquirida/epidemiologia , Corticosteroides/antagonistas & inibidores , Soronegatividade para HIV , Humanos , Masculino , Modelos Biológicos , Pneumonia por Pneumocystis/induzido quimicamenteRESUMO
Human immunodeficiency virus type 1 (HIV1) RNA was quantitated in the plasma of HIV1-seropositive patients using a simplified guanidinium-based extraction technique, reverse transcriptase (RT) and the polymerase chain reaction (PCR). Plasma samples were obtained from 15 HIV1-seronegative individuals and 38 HIV1-seropositive patients. Following the extraction of RNA from plasma using "RNAzol", HIV1 RNA was reverse-transcribed using random hexamers, amplified by PCR and then detected by solution oligonucleotide hybridization. Of the 15 HIV1-seronegative individuals, 14 were negative for HIV1 RNA by RT-PCR. One high-risk patient who was HTLV-I-seropositive but HIV1-seronegative was found to be positive for HIV1 RNA by RT-PCR. All 38 HIV1-seropositive patients were positive for HIV1 RNA by this technique. The HIV1 RNA levels in plasma varied from 800 to 500,000 copies/ml. Patients with advanced clinical disease tended to have HIV1 RNA levels above 25,000 copies/ml. In patients studied serially, an increase in plasma HIV1 RNA correlated with a progressive decline in CD4+ T cells and a deteriorating clinical course. The simplified quantitative RT-PCR assay for HIV1 RNA provides a useful tool for the evaluation and management of HIV disease.
Assuntos
Infecções por HIV/virologia , HIV-1/isolamento & purificação , Reação em Cadeia da Polimerase , RNA Viral/sangue , Progressão da Doença , Genes gag , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Soronegatividade para HIV , Soropositividade para HIV/sangue , Soropositividade para HIV/virologia , HIV-1/genética , Humanos , RNA Viral/efeitos dos fármacos , Sensibilidade e Especificidade , Transcrição Gênica , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: Promotion of cell-mediated immunity appears to be an important goal in the control of HIV infection. Topical dinitrochlorobenzene (DNCB) stimulates systemic cell-mediated immunity via the induction of cutaneous delayed-type hypersensitivity. OBJECTIVE: Our goal was to evaluate the clinical and immunologic effects of chronic DNCB application in a group of 24 HIV-infected patients. METHODS: We observed the patients for a mean of 28 months (range, 14 to 44 months). Of the 24 patients, 13 continued weekly DNCB application throughout the study (the compliant group), and 11 discontinued DNCB use after a mean of 10.9 months (the noncompliant group). RESULTS: Two of the 13 compliant patients progressed to AIDS; none of these patients died. In contrast, AIDS developed in 5 of the 11 noncompliant patients and four of these patients died. Analysis of lymphocyte subsets revealed significant increases in natural killer cells and activated/cytotoxic CD8 T-cell subsets in the compliant group. In contrast, these cellular immune-related lymphocyte subsets decreased in the noncompliant subjects. Although CD4 T-cell levels decreased in both groups, there was a significantly greater drop in the noncompliant patients. CD8+CD38+ T cells increased significantly in both groups. CONCLUSION: Chronic DNCB application appears to have a beneficial clinical and immunomodulatory effect in HIV-infected patients.
Assuntos
Dinitroclorobenzeno/uso terapêutico , Infecções por HIV/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Antígenos CD/análise , Relação CD4-CD8 , Citometria de Fluxo , Infecções por HIV/tratamento farmacológico , Humanos , Imunidade Celular , Subpopulações de Linfócitos , Masculino , Cooperação do PacienteRESUMO
Although mass vaccination programs have resulted in the eradication of a number of human infectious diseases, vaccine contamination has been a persistent concern. In particular, it is now known that the early polio vaccines were contaminated with at least one monkey virus, SV40. The transfer of monkey viruses to man via contaminated vaccines is particularly relevant to the acquired immunodeficiency syndrome (AIDS), since the causative agent of AIDS, human immunodeficiency virus (HIV), is thought to be derived from a simian precursor virus. Furthermore, human infection with this virus appears to be a relatively recent event. We hypothesize that the AIDS pandemic may have originated with a contaminated polio vaccine that was administered to inhabitants of Equatorial Africa from 1957 to 1959. The mechanism of evolution of HIV from this vaccine remains to be determined.
Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , Chlorocebus aethiops/microbiologia , Surtos de Doenças , Contaminação de Medicamentos , Vacina Antipólio de Vírus Inativado/efeitos adversos , Acidentes , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/história , Animais , Células Cultivadas/microbiologia , Cricetinae , República Democrática do Congo/epidemiologia , HIV-1/isolamento & purificação , História do Século XX , Humanos , Macaca/microbiologia , Neoplasias Experimentais/microbiologia , Vacina Antipólio de Vírus Inativado/história , Vacina Antipólio Oral/efeitos adversos , Vacina Antipólio Oral/história , Síndrome de Imunodeficiência Adquirida dos Símios/microbiologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Vírus 40 dos Símios/isolamento & purificação , Vírus 40 dos Símios/patogenicidade , ZoonosesAssuntos
Dinitroclorobenzeno/uso terapêutico , Infecções por HIV/tratamento farmacológico , Administração Cutânea , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Dinitroclorobenzeno/administração & dosagem , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Pele/efeitos dos fármacos , Pele/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologiaRESUMO
Dendritic cells, the primary antigen presenting cells of the human immune system, are heavily infected with human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS). Dinitrochlorobenzene (DNCB) is a contact sensitizing agent that acts as a potent immune modulator of dendritic cells. In this pilot study, we examined the safety and efficacy of topical DNCB application in patients with early HIV disease. Topical DNCB was well tolerated by these patients, with an adverse reaction rate of 10%. CD4+ T-cell counts remained stable with repeated DNCB use. In contrast, CD8+ T-cell counts and natural killer cells increased significantly following DNCB sensitization. This increase in CD8+ T-cell and natural killer cell subsets was accompanied by a decrease in HIV replication, as measured by serum HIV RNA levels. Based on this pilot study, we conclude that topical DNCB is safe in early HIV disease and may decrease viral load via a systemic effect on dendritic cells, CD8+ T-cells and natural killer cells. These results require confirmation in larger controlled trials.
Assuntos
Dinitroclorobenzeno/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Administração Cutânea , Administração Tópica , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Dinitroclorobenzeno/administração & dosagem , Dinitroclorobenzeno/efeitos adversos , Infecções por HIV/imunologia , HIV-1/genética , Humanos , Células Matadoras Naturais/imunologia , Masculino , Projetos Piloto , RNA Viral/análise , Linfócitos T Reguladores/imunologia , Replicação ViralRESUMO
Recent studies suggest that antigen-presenting cells (dendritic cells) may play a key role in the pathogenesis of human immunodeficiency virus (HIV) infection. This observation makes new immunomodulatory treatment strategies desirable. Topical dinitrochlorobenzene (DNCB) is discussed as a possible treatment modality in the context of its proven therapeutic uses and its immunomodulatory effect on dendritic cells. DNCB may be a safe, inexpensive, and widely available treatment option for HIV disease.