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1.
AIDS ; 24(1): 35-43, 2010 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-19779318

RESUMO

OBJECTIVES: To determine whether oral HIV-1 exposure incites a persistent systemic anti-HIV-1 response in exposed uninfected individuals of discordant couples of men who have sex with men, and whether this response associates with HIV-1 exposure measured by viral load in the HIV-positive partners. METHODS: Plasma were collected from exposed uninfected individuals (n = 25), HIV-positive partners (n = 25) and low-risk controls (n = 22). A peripheral blood mononuclear cells-based neutralization assay was used to test these samples against three primary HIV-1 isolates. Self-reported questionnaires described routes of HIV-1-exposure, and clinical records documented viral loads in HIV-positive partners. RESULTS: At enrollment, plasma samples from seven of 25 exposed uninfected individuals neutralized at least two of the three HIV-1 isolates. No samples from the 22 controls neutralized any HIV-1 isolate (P = 0.01). Of these seven exposed uninfected individuals, six retained neutralization capacity during follow-up. Neutralization capacity among exposed uninfected individuals associated with the highest measured viral load of their respective partners (P = 0.01) and also time since highest viral load (P = 0.02). Purified plasma immunoglobulin (Ig) A1-mediated neutralization was observed in six of the seven samples, whereas none of the IgA1-depleted plasma samples neutralized HIV-1. The neutralizing IgA1 was not HIV envelope specific as detected by ELISA and western blot. CONCLUSION: Orally exposed uninfected men who have sex with men can mount neutralizing anti HIV-1 activity in plasma, mediated primarily by non-HIV envelope-specific IgA1. Neutralization was associated with previous measured highest viral load in the HIV-positive partner, as well as time elapsed since the peak viral load. Neutralization also persisted over time in spite of a continuous low viral exposure.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Imunoglobulina A/imunologia , Carga Viral/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-HIV/biossíntese , Infecções por HIV/virologia , Soronegatividade para HIV/imunologia , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , Homossexualidade Masculina , Humanos , Imunidade nas Mucosas/imunologia , Masculino , Mucosa Bucal/imunologia , Mucosa Bucal/virologia , Parceiros Sexuais , Inquéritos e Questionários
2.
AIDS ; 23(3): 329-33, 2009 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-19114861

RESUMO

OBJECTIVE: To determine whether oral sexual exposure to HIV-1 (HIV) results in HIV-neutralizing activity in saliva of uninfected men who have sex with infected men? DESIGN: Saliva samples were collected from HIV IgG seronegative men (n = 25) whose male partners were HIV infected and from low-risk healthy controls (n = 22) and analyzed for HIV-neutralizing capacity. METHODS: The presence of neutralizing activity in saliva was tested in a peripheral blood mononuclear cell-based assay using primary HIV isolates. Self-reporting questionnaires described the individuals' sexual behaviors and routes of possible HIV exposure. RESULTS: Of 25 exposed, uninfected individuals (EUI), 21 reported receptive unprotected oral intercourse, whereas three of the 25 reported unprotected anal receptive intercourse. Whole saliva from both EUI and low-risk healthy controls contained HIV-neutralizing activity. However, a significant difference was seen when analyzing the salivary IgA1 fraction: 13 of 25 EUI neutralized HIV, whereas none of the 22 controls had this capacity. The neutralizing capacity of the EUI males persisted during 2 years of follow-up. CONCLUSION: Unprotected oral sex evokes a salivary IgA1-mediated HIV-neutralizing response that persists over time during continuous exposure in uninfected male partners of infected men.


Assuntos
Anticorpos Anti-HIV/biossíntese , Infecções por HIV/imunologia , HIV-1/imunologia , Homossexualidade Masculina , Comportamento Sexual , Adulto , Estudos de Coortes , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Imunidade nas Mucosas , Imunoglobulina A/biossíntese , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Saliva/imunologia , Sexo sem Proteção
3.
Scand J Infect Dis ; 36(1): 40-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15000558

RESUMO

Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir-based ART in 29 patients who have been followed for 28 months thereafter. Virologic failure occurred within 3 months in 21% (6/29) of the patients, and abacavir hypersensitivity in 1 individual. The remaining 22 patients continue to have HIV RNA < 50 copies/ml after 28 months with a CD4 increase from 605 +/- 265 x 10(6)/l to 798 +/- 366 x 10(6)/l (p < 0.001). All virologic failing patients had been on long-term unsuccessful nucleoside reverse transcriptase inhibitor (NRTI) therapy before PI-ART as compared to 32% (7/22) of the virologic non-failing patients (p < 0.01). The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). The LDL cholesterol and triglyceride values decreased and the HDL cholesterol increased after the switch to abacavir-based ART (p < 0.01, p < 0.05, p < 0.05, respectively). In conclusion, viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V1181 RT mutation, persisting despite long term viral control. The selection process for patients suitable for treatment simplification to abacavir-based ART should contain a detailed antiretroviral treatment history.


Assuntos
Didesoxinucleosídeos/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Mutação , DNA Polimerase Dirigida por RNA/genética , Inibidores da Transcriptase Reversa/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Probabilidade , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Método Simples-Cego , Estatísticas não Paramétricas , Falha de Tratamento , Carga Viral , Replicação Viral/efeitos dos fármacos
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