RESUMO
BACKGROUND: HIV-1(+) individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+) T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression. METHODOLOGY/PRINCIPAL FINDINGS: CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+) individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+) patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years. CONCLUSIONS: Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.
Assuntos
Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Linfócitos T/patologia , Linfócitos T/virologia , Timo/imunologia , Timo/virologia , Adulto , Idoso , Proliferação de Células , Feminino , Seguimentos , Antígenos HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Especificidade da Espécie , Linfócitos T/imunologia , Fatores de Tempo , Proteínas Virais/imunologiaRESUMO
Restoration of the immune system following HAART is not without its adverse effects. We describe a case of severe cutaneous ulceration secondary to cytomegalovirus (CMV) infection in an HIV-1-seropositive man following the initiation of HAART in the absence of active CMV retinitis and discuss the likely mechanisms associated with its development.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , Dermatopatias Virais/complicações , Úlcera Cutânea/etiologia , Adulto , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Dermatopatias Virais/tratamento farmacológico , Dermatopatias Virais/patologia , Úlcera Cutânea/tratamento farmacológicoAssuntos
Fármacos Anti-HIV/efeitos adversos , Sonhos , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Transtornos do Sono-Vigília , Adulto , Quimioterapia Combinada , HIV-1 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Despite major advances in HIV research, eradication of HIV from the body is not yet possible. However, current antiretroviral (ARV) therapy can achieve disease control via viral suppression below the limits of detection of currently available assays. This has led to a marked decline in morbidity and mortality associated with the development of opportunistic infections and malignancies. Since viral suppression appears to be the most achievable goal of current therapy, there arises a need for new and more potent ARV agents in order to maintain viral suppression. Many of the currently available protease inhibitors (PIs) have a high protein-binding ability, short plasma half-life [1] and pharmacokinetic interactions with food or other drugs [2]. This can result in sub-optimal plasma drug concentrations, which may allow the virus to break through and replicate, leading to the development of resistant mutants [1]. Lopinavir/ritonavir (LPV/r; Kaletra, Abbott Laboratories) is a new PI consisting of a co-formulation of lopinavir and low-dose ritonavir. The sub-therapeutic dose of ritonavir (a potent cytochrome P450 [CYP] 3A4 inhibitor) inhibits the metabolism of lopinavir, resulting in higher lopinavir concentrations than when lopinavir is administered alone [3]. This pharmacokinetic interaction is associated with a high lopinavir trough level:wild type median effective concentration (EC(50)) ratio and good general tolerability when compared with other currently licensed PIs [4]. The concept of pharmacokinetic enhancement - boosting - is not new as ritonavir has previously been utilised in this context with other PIs. The relationship between plasma and intracellular drug levels has yet to be clarified. What has been ascertained from pharmacokinetic studies thus far is the correlation between ARV trough plasma concentrations (C(min)) and virological outcome [5,6]. LPV/r exemplifies how the pharmacokinetic profile of a drug can be modified to attain sufficient C(min) to suppress pheno- and genotypically resistant viral strains, as well as provide a pharmacological barrier to the emergence of resistance [7]. LPV/r reduces pill-burden and aids compliance, as shown by encouraging results in the treatment of both ARV-naive and -experienced patients.