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1.
J Pediatric Infect Dis Soc ; 9(2): 228-231, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30753640

RESUMO

The reduction in human immunodeficiency virus (HIV) transmission through breastmilk with maternal combination antiretroviral therapy (cART) has led many pregnant women living with HIV and healthcare providers to question exclusive formula feeding in resource-rich settings. Here, we describe cART prophylaxis in 3 breastfed infants whose mothers had sustained virologic suppression; all 3 of these infants remained uninfected.


Assuntos
Antirretrovirais/uso terapêutico , Aleitamento Materno , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Recursos em Saúde , Humanos , Lactente , Masculino , Adesão à Medicação , Ontário
2.
Gene Ther ; 21(2): 175-87, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24305417

RESUMO

Current human immunodeficiency virus type I (HIV) gene therapy strategies focus on rendering HIV target cells non-permissive to viral replication. However, gene-modified cells fail to accumulate in patients and the virus continues to replicate in the unmodified target cell population. We have designed lentiviral vectors encoding secreted anti-HIV proteins to protect both gene-modified and unmodified cells from infection. Soluble CD4 (sCD4), a secreted single chain variable fragment (sscFv(17b)) and a secreted fusion inhibitor (sFI(T45)) were used to target receptor binding, co-receptor binding and membrane fusion, respectively. Additionally, we designed bi- and tri-functional fusion proteins to exploit the multistep nature of HIV entry. Of the seven antiviral proteins tested, sCD4, sCD4-scFv(17b), sCD4-FI(T45) and sCD4-scFv(17b)-FI(T45) efficiently inhibited HIV entry. The neutralization potency of the bi-functional fusion proteins sCD4-scFv(17b) and sCD4-FI(T45) was superior to that of sCD4 and the Food and Drug Administration-approved fusion inhibitor T-20. In co-culture experiments, sCD4, sCD4-scFv(17b) and sCD4-FI(T45) secreted from gene-modified producer cells conferred substantial protection to unmodified peripheral blood mononuclear cells. In conclusion, continuous delivery of secreted anti-HIV proteins via gene therapy may be a promising strategy to overcome the limitations of the current treatment.


Assuntos
Fármacos Anti-HIV/farmacologia , Antígenos CD4/farmacologia , Terapia Genética/métodos , Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Lentivirus/genética , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/farmacologia , Produtos Biológicos/farmacologia , Antígenos CD4/genética , Linhagem Celular Tumoral , Vetores Genéticos/administração & dosagem , Células HEK293 , Humanos , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/farmacologia , Estados Unidos , United States Food and Drug Administration
3.
J Adolesc Health ; 25(5): 358-66, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10551667

RESUMO

PURPOSE: The purposes of this study were: (a) to identify human immunodeficiency virus (HIV) prevalence in Toronto street youth through paired blood and saliva specimens; (b) to identify the HIV risk and prevention behaviors of street involved youth; and (c) to identify demographic or other factors that may contribute to the risk of street youth becoming infected with HIV/acquired immunodeficiency syndrome (AIDS) in the future. METHODS: This was a cross-sectional convenience study of street-involved youth aged 14-25 years. The youth participated in interviews to identify HIV-related knowledge and personal risk and preventive behaviors. Following interviews, they were asked to provide a saliva sample, blood spot, or both. They could refuse one or both samples without jeopardizing their involvement or receiving an honorarium. Two males were the only participants who declined to provide a sample. RESULTS: Fifteen of 695 (2.2%) youth tested positive for HIV infection. All were male, ranging in age from 18 to 25 years. Same and opposite sex, intravenous (IV) drug use, prostitution, and incarceration were risk factors associated with positive HIV test results. The rate of HIV infection was seven times greater for the group 20 years of age and older (20-25) compared to the younger group aged 14-9 years. The proportion testing positive for HIV from small cities, towns, and rural communities in Ontario was 40%; yet, they represented 21% of the study population. Most (57%) youth had been on their own for no more than 3 years and had moved frequently. Nearly two thirds (60%) had stayed in hostels or homeless shelters in the previous 6 months. CONCLUSION: Street youth in Canada are at high risk of HIV infection with their risk increasing with age. Unprotected (same and opposite) sex, IV drug use, prostitution and incarceration were linked to their HIV infections. The high level of mobility identified by street youth challenges governments, communities, and public health officials to develop appropriate prevention strategies and to carefully monitor the spread of HIV infection in this vulnerable population.


Assuntos
Infecções por HIV/epidemiologia , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pessoas Mal Alojadas/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Ontário/epidemiologia , Prevalência , Fatores de Risco , Saliva/virologia , População Urbana
4.
Am J Ophthalmol ; 127(5): 550-8, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10334348

RESUMO

PURPOSE: To describe the ocular and systemic features of children with cytomegalovirus retinitis and their disease outcomes. METHODS: Review of all cases of cytomegalovirus retinitis diagnosed or treated at a tertiary care pediatric hospital during a 10-year period. RESULTS: Nine immunocompromised children younger than 16 years were diagnosed as having cytomegalovirus retinitis. The underlying causes of immunocompromise were severe combined immunodeficiency syndrome (n = 2), severe combined immunodeficiency syndrome after bone marrow transplantation (n = 1), acquired immunodeficiency syndrome (AIDS) (n = 2), AIDS and previous bone marrow transplantation for leukemia (n = 1), immunosuppressive therapy after renal transplantation (n = 1), chemotherapy for leukemia (n = 1), and congenital cytomegalovirus infection (n = 1). Five children (56%) had symptomatic extraocular cytomegalovirus infection. Only two children reported visual symptoms with cytomegalovirus retinitis at initial examination. Cytomegalovirus retinitis was bilateral in eight children (89%) and involved the posterior pole in at least one eye of all nine children. Four children (44%) died within 10 months of being diagnosed with cytomegalovirus retinitis. The remaining five children were alive, with follow-up ranging from 14 to 70 months. Successful bone marrow transplantation in one child and discontinuation of immunosuppressive medications in two children improved systemic immune function and permitted discontinuation of anticytomegaloviral therapy. CONCLUSION: Pediatric cytomegalovirus retinitis is often asymptomatic and bilateral and involves the posterior pole at initial examination. Recovery of systemic immune function may occur in some children. Evaluation of children at risk and prompt treatment of cytomegalo. virus retinitis are important to prevent long-term visual morbidity.


Assuntos
Retinite por Citomegalovirus/complicações , Síndromes de Imunodeficiência/complicações , Terapia de Imunossupressão , Adolescente , Antivirais/uso terapêutico , Criança , Pré-Escolar , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/mortalidade , Retinite por Citomegalovirus/patologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Taxa de Sobrevida , Resultado do Tratamento , Acuidade Visual
5.
AIDS ; 12(14): 1785-91, 1998 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-9792379

RESUMO

OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged < 13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radioimmunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: The study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/l, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.01 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Eritropoetina/sangue , Infecções por HIV/sangue , Zidovudina/uso terapêutico , Anemia/prevenção & controle , Bahamas , Canadá , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Hemoglobinas/análise , Humanos , Lactente , Masculino , Insuficiência Renal/sangue
6.
AIDS ; 12(14): 1785-91, Oct. 1, 1998.
Artigo em Inglês | MedCarib | ID: med-1379

RESUMO

OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged <13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radio-immunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: Ths study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/I, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.001 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.(Au)


Assuntos
Criança , Pré-Escolar , Estudo Comparativo , Feminino , Humanos , Masculino , Lactente , Fármacos Anti-HIV/uso terapêutico , Eritropoetina/sangue , Zidovudina/uso terapêutico , Infecções por HIV/sangue , Bahamas , Canadá , Estudos Transversais , Hemoglobinas/análise , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/sangue , Anemia/prevenção & controle
7.
J Clin Microbiol ; 36(7): 2096-8, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9650972

RESUMO

We have developed small-volume (50 or 250 microl)-format branched-DNA assays for human immunodeficiency virus type 1 (HIV-1) RNA for use with specimens in which the volume is limited and/or a high viral load is anticipated. These formats exhibited good correlation with the standard 1-ml format; high specificity, reproducibility, and linearity; and no significant difference in the quantification of HIV-1 subtypes.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , RNA Viral/sangue , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , DNA Viral , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga Viral
8.
Pharmacotherapy ; 17(6): 1198-209, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9399602

RESUMO

Polypharmacy is commonly encountered in human immunodeficiency virus (HIV)-positive patients, and the risk and frequency of drug-drug interactions are significant in this patient population. Most HIV-positive patients receive the antiretroviral drug zidovudine (3'-azido-3'-deoxythymidine, ZDV), the first drug to be approved for the treatment of HIV. Many drug interactions with ZDV have already been reported. As HIV pharmacotherapy becomes more complex, the potential for drug-drug interactions is likely to increase significantly.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Zidovudina/efeitos adversos , Animais , Fármacos Anti-HIV/uso terapêutico , Interações Medicamentosas , Humanos , Farmacocinética , Zidovudina/uso terapêutico
9.
Pediatr AIDS HIV Infect ; 8(1): 15-22, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11361507

RESUMO

OBJECTIVE: To review the impact of routine follow-up cranial computed tomography (CT) scans on the management of children with human immunodeficiency virus (HIV) infection. DESIGN: Longitudinal data collected from 58 HIV-infected children followed in one center for mean of 3.8 +/- 1.8 years. SETTING: HIV/AIDS pediatric program following over 90% of the identified HIV-infected children in one region in Canada. RESULTS: The baseline CT scans showed intracranial abnormalities in 35 of 58 children (60%). In five children with basal ganglia calcifications (BGC) without cerebral atrophy, there has not been progressive encephalopathy. For the 43 children who had serial CT scans for routine follow-up, 34 (79%) had changes in the scans that were concordant with the clinical assessment. In all but five children with progressive ventricular and sulcal dilatation on CT scan, there was simultaneous clinical evidence of encephalopathy. Those five children were already on antiretroviral therapy, and therapy was not changed in response to the CT scan findings. CONCLUSION: Baseline CT scans provide useful diagnostic and prognostic information. Further research is needed to evaluate the role of cranial CT imaging in the management of pediatric HIV encephalopathy.


Assuntos
Complexo AIDS Demência/diagnóstico por imagem , Assistência ao Convalescente/métodos , Tomografia Computadorizada por Raios X , Complexo AIDS Demência/etiologia , Complexo AIDS Demência/prevenção & controle , Adolescente , Criança , Pré-Escolar , Hemofilia A/complicações , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Estudos Longitudinais , Prognóstico , Reprodutibilidade dos Testes , Reação Transfusional
10.
Arch Pediatr Adolesc Med ; 150(11): 1186-92, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8904861

RESUMO

OBJECTIVES: To identify immunosuppressed children who are at risk of cytomegalovirus (CMV) retinitis developing and to evaluate the use of laboratory results for identifying this risk. DESIGN: Prospective cohort and retrospective case-control series. SETTING: University hospital pediatric referral center. PATIENTS: Fifty-six consecutive immunocompromised children (ie, the prospective group) with laboratory evidence consistent with acute or recently acquired CMV infection, which was defined as CMV cultured from the blood, urine, nasopharynx, or biopsy specimen, recent seroconversion, a 4-fold increase in the CMV antibody titer, or an antibody titer of 1:512 or greater. Ninety-three immunocompromised children (ie, the retrospective group) with acute CMV or previous CMV exposure, which was defined as a CMV titer of 1:4 or greater and less than 1:512. MAIN OUTCOME MEASURE: Occurrence of CMV retinitis. RESULTS: Cytomegalovirus retinitis developed in 3 children in the prospective group and in 4 children in the retrospective group. The causes of immunosuppression were severe combined immunodeficiency syndrome (n = 2), severe combined immunodeficiency syndrome status post bone marrow transplantation (n = 1), acquired immunodeficiency syndrome (n = 1), and acquired immunodeficiency syndrome status post bone marrow transplantation for leukemia (n = 1), renal transplantation (n = 1), and chemotherapy for leukemia (n = 1). Cytomegalovirus retinitis was associated with a positive CMV culture result from the urine (P = .03) or nasopharynx (P < .001) in the retrospective group. In the retrospective group, one child with congenital CMV infection and CMV retinitis was excluded from analysis because laboratory tests for CMV were not obtained prior to ganciclovir therapy. CONCLUSIONS: Cytomegalovirus retinitis is uncommon in children compared with adults; it occurred in 5% of the children in our series. A screening ophthalmologic examination should be considered in immunocompromised children with positive CMV laboratory results, particularly positive results of urine or nasopharynx cultures.


Assuntos
Retinite por Citomegalovirus/diagnóstico , Hospedeiro Imunocomprometido , Adolescente , Anticorpos Antivirais/análise , Estudos de Casos e Controles , Criança , Citomegalovirus/imunologia , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/imunologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Estudos Prospectivos
11.
AIDS ; 10(11): 1191-8, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8883579

RESUMO

OBJECTIVE: We examined the effect of HIV infection on src-family protein tyrosine kinase (PTK) activity to determine if alterations in src-family PTK activity could contribute to the HIV-related chronic immune system activation observed in patients infected with HIV. METHODS: Jurkat, a CD4+ human T lymphocyte cell line was infected with HIV IIIB. Kinase activity was determined by in vitro immune complex kinase assays using antibodies specific for the src-family PTKs, p56lck, p59fyn and p60c-src expressed in T lymphocytes. PTK protein and total phosphotyrosine levels were assessed by Western blotting. The role of the gp120-CD4-Lck interaction in HIV-related PTK activation was determined using gp 120-treated Jurkat cells and HIV-infection of JCaM 1.6 cells, a Jurkat-derived cell line that lacks p56lck. RESULTS: Cells infected with HIV for 24 h exhibited increased levels of total tyrosine phosphorylation and enhanced src-family PTK activity without altered levels of expression of src-family kinases. The activity of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family PTK activation was not a function of the gp120-CD4-Lck interaction and occurred in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and activation of the HIV genome is not required. CONCLUSIONS: HIV-related activation of src-family PTK is a response of the cell to early stages of the virus life cycle, possibly either membrane fusion or viral uncoating. These results indicate that endogenous src-family PTKs may play a role in HIV-related immune activation and dysfunction. Moreover, activation of src-family PTK may be a mechanism used by the virus to facilitate some aspect of its own life cycle.


Assuntos
HIV-1/fisiologia , Quinases da Família src/metabolismo , Catálise , Ativação Enzimática , Proteína gp120 do Envelope de HIV/metabolismo , Transcriptase Reversa do HIV/metabolismo , Humanos , Células Jurkat , Cinética , Fosfotirosina/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-8673550

RESUMO

The Commonwealth of the Bahamas has one of the highest rates of acquired immunodeficiency syndrome (AIDS) in the English-speaking Caribbean. A seroprevalence study of pregnant women attending antenatal clinics in New Providence in 1990-91 showed that of 3,914 pregnant women tested, 2.9% were human immunodeficiency virus (HIV) infected. Women born in the Bahamas constituted 79.2% of the women tested; 17.7% were born in Haiti. The rate of HIV infection was 2.5% in the Bahamian women as compared with 4.5% in those born in Haiti. The highest incidence was in women aged 25-34 years and in women who had multiple pregnancies. There was a significant association with a history of crack cocaine use by the Bahamian women. There was also a significant association between a lack of education and HIV infection in this group. There was a lower rate of condom use among women with less education and also among women in common-law relationships, but the association of lack of condom use and HIV infection did not reach statistical significance.


Assuntos
Infecções por HIV/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Bahamas/epidemiologia , Preservativos/estatística & dados numéricos , Cocaína Crack , Escolaridade , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/etiologia , Haiti/etnologia , Humanos , Incidência , Jamaica/etnologia , Abuso de Maconha/complicações , Estado Civil , Paridade , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Prevalência , Fatores de Risco , Fumar/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Sífilis/complicações , Estados Unidos/etnologia
13.
Artigo em Inglês | MedCarib | ID: med-3174

RESUMO

The Commonwealth of the Bahamas has one of the highest rates of acquired immunodeficiency syndrome (AIDS) in the English-speaking Caribbean. A seropositive study of the pregnant women attending antenatal clinics in New Providence in 1990-91 showed that of 3,914 pregnant women tested, 2.9 percent were human immunodeficiency virus (HIV) infected. Women born in the Bahamas constituted 79.2 percent of the women tested; 17.7 percent were born in Haiti. The rate of HIV infection was 2.5 percent in the Bahamian women as compared with 4.5 percent in those born in Haiti. The highest incidence was in women aged 25-34 years and in women who had multiple pregnancies. There was a significant association with a history of crack cocaine use by the Bahamian women. There was also a significant association between a lack of education and HIV infection in this group. There was a lower rate of condom use among women with less education and also among women in common-l


Assuntos
Humanos , Feminino , Adolescente , Adulto , Gravidez , Infecções por HIV/epidemiologia , Infecções por HIV/etiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/etiologia , Distribuição por Idade , Preservativos/estatística & dados numéricos , Cocaína Crack , Escolaridade , Anticorpos Anti-HIV/sangue , Incidência , Abuso de Maconha , Estado Civil , Paridade , Prevalência , Fatores de Risco , Tabagismo/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Sífilis/complicações , Estados Unidos/etnologia , Bahamas/epidemiologia , Haiti/epidemiologia , Jamaica/etnologia
14.
J Infect Dis ; 172(5): 1375-9, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7594682

RESUMO

Studies examining specific antibodies directed against antigenic components of human immunodeficiency virus (HIV), as potential markers of progression to AIDS, have reported inconsistent results. We used reflectance densitometry and survival analysis to determine whether single quantitative measures of HIV-specific antibodies predicted progression to AIDS in a prospective cohort of 159 HIV-infected homosexual men. Lowered baseline levels of p24 antibody and p24/gp41 antibody ratio were independent predictors of progression to AIDS and retained statistical significance after simultaneously controlling for CD4:CD8 ratio, age, use of zidovudine, and clinical symptoms. Quantitative measures of p24 antibody and p24/gp41 antibody ratio warrant further study with regards to their clinical application as markers of HIV disease progression.


Assuntos
Síndrome de Imunodeficiência Adquirida/fisiopatologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/fisiopatologia , Soropositividade para HIV/fisiopatologia , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Fatores Etários , Análise de Variância , Bissexualidade , Relação CD4-CD8 , Progressão da Doença , Seguimentos , Proteína do Núcleo p24 do HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , Soropositividade para HIV/sangue , Soropositividade para HIV/imunologia , Homossexualidade Masculina , Humanos , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Fatores de Tempo , Zidovudina/uso terapêutico
15.
AIDS Res Hum Retroviruses ; 11(2): 249-56, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7742039

RESUMO

The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , Apoptose/imunologia , Antígenos HIV/imunologia , HIV-1/imunologia , Linfócitos T/imunologia , Síndrome de Imunodeficiência Adquirida/fisiopatologia , Células Cultivadas , Citotoxicidade Imunológica/efeitos dos fármacos , Antígenos HIV/farmacologia , Humanos , Interleucina-2/farmacologia , Proteínas Recombinantes/farmacologia , Linfócitos T/efeitos dos fármacos
16.
Viral Immunol ; 7(2): 81-95, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7848511

RESUMO

CTL activity against HIV-1 antigens expressed on HLA-A-matched EBV-transformed B target cells was detected in 33% (6/18) of freshly isolated PBMC (FPBMC) from patients in the early stages of HIV-1 infection (CDCII). No CTL activity was detected in FPMBC in patients with AIDS (CDCIV). However, the presence of CTL activity did not correlate with the expression of CTL activation markers. A dual-color flow cytometric examination revealed that the CD8+ lymphocytes bearing the memory (CD29) and activation (S6F1) surface molecules increased in number as the HIV-1 infection progressed. This functional and phenotypic discrepancy in memory CD8+ lymphocytes suggests that the memory CD8+ lymphocytes have lost cytotoxic function and become "paralyzed" as the HIV disease progresses. Incubation of PBMC of HIV(+) patients with rIL-2 reactivated predominantly HIV-specific CTL. However, rIL-2 stimulation also activated a "polyclonal or polyreactive" cytotoxic function. The reactivation of CTL function is rIL-2 dosage dependent and the amount of rIL-2 required for reactivation is associated with the severity of the disease. HIV antigen specific CTL in HIV(+) patients can be selectively expanded by HIV antigen stimulation in the presence of rIL-2. These results suggest that the in vivo IL-2 deficiency occurring in HIV-1 infection may be responsible in part for the "paralysis" of HIV specific CTL activity. Such activity can be rescued nonspecifically by exogenous rIL-2 stimulation and expanded specifically by HIV-1 antigen stimulation.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Ativação Linfocitária/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Superfície/imunologia , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica/imunologia , Citometria de Fluxo , Antígenos HIV/imunologia , Antígenos HLA-A/imunologia , Humanos , Memória Imunológica/imunologia , Imunofenotipagem , Interleucina-2/imunologia , Proteínas Recombinantes/imunologia
17.
Ann Epidemiol ; 3(3): 272-80, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8275200

RESUMO

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.


Assuntos
Bissexualidade , Homossexualidade , Transtornos Relacionados ao Uso de Substâncias , Síndrome de Imunodeficiência Adquirida/prevenção & controle , Síndrome de Imunodeficiência Adquirida/transmissão , Adulto , Consumo de Bebidas Alcoólicas , Estudos de Coortes , Humanos , Masculino , Fatores de Risco
18.
Can J Infect Dis ; 4(6): 333-40, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22346469

RESUMO

Pneumocystis carinii pneumonia (PCP) is associated with significant mortality and morbidity among infants infected with human immunodeficiency virus (HIV). The preferred prophylaxis strategy for such infants is a subject of debate. Medical decision analysis was used to determine the preferred strategy for primary PCP prophylaxis among asymptomatic HIV-infected infants less than one year of age, and to determine the thresholds at which different variables influence decision making. Utility measures (health state preference values) were used to determine whether prophylaxis should be given to all, some or no infants. In this regard, some infants would receive prophylaxis if baseline CD4 counts are fewer than 1500 cells/mm(3). The results suggest that the preferred option is to give prophylaxis to all asymptomatic HIV-infected infants despite CD4 counts, if the risk of PCP is equal to or greater than 25%. However, if the risk of PCP is less than 25%, prophylaxis is recommended for those infants with CD4 counts of fewer than 1500 cells/mm(3). The results complement current guidelines regarding PCP prophylaxis for HIV-infected infants.

19.
J Clin Epidemiol ; 45(3): 245-53, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1569421

RESUMO

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Soropositividade para HIV , Sorodiagnóstico da AIDS , Adulto , Relação CD4-CD8 , Estudos de Coortes , Proteína do Núcleo p24 do HIV/isolamento & purificação , Humanos , Ativação Linfocitária , Masculino , Análise Multivariada , Análise de Regressão , Comportamento Sexual , Parceiros Sexuais , Subpopulações de Linfócitos T
20.
Int J Epidemiol ; 21(1): 131-5, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1544744

RESUMO

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.


Assuntos
Síndrome de Imunodeficiência Adquirida/epidemiologia , Soroprevalência de HIV , Adulto , Estudos de Coortes , Humanos , Modelos Logísticos , Masculino , Ontário/epidemiologia , Probabilidade , Estudos Soroepidemiológicos
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