RESUMEN
OBJECTIVES: To determine a quantitative herpes simplex virus (HSV) DNA threshold in lower respiratory tract specimens that correlates with positive viral culture and clinical outcomes. METHODS: Bronchoalveolar lavage and bronchial wash samples from 53 HSV culture-positive and 61 culture-negative matched controls were tested using HSV-1 and HSV-2 quantitative polymerase chain reaction (qPCR). RESULTS: Median viral culture turnaround time was 21.8 days and 9.9 days for culture-negative and culture-positive specimens, respectively. Using an HSV-1 viral load threshold of 1.62 × 103 copies/mL, there was 93% agreement with viral culture. An HSV-1 viral load ≥1.3 × 104 copies/mL was associated with worse clinical outcome compared to a viral load <1.3 × 104 copies/mL (hazard ratio [HR] = 4.27, P = .017), and there was a trend of worse outcome compared to patients with undetectable HSV-1 DNA (HR = 1.60, P = .056). CONCLUSIONS: qPCR has clinical utility for rapid accurate identification of HSV-1 in lower respiratory tract specimens.
Asunto(s)
Herpes Simple/diagnóstico , Herpesvirus Humano 1/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Infecciones del Sistema Respiratorio/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Femenino , Herpes Simple/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Receptores de Trasplantes , Adulto JovenRESUMEN
BACKGROUND: We evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection. METHODS: Cryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured in plasma, whereas T-cell activation levels, defined as the frequencies of CD4 and CD8 T cells coexpressing HLA-DR and CD38, were measured in peripheral blood mononuclear cells. RESULTS: D-dimer levels were significantly lower at viral suppression (P = 0.031), whereas CRP and sCD14 levels remained similar to pre-ART levels. At viral suppression, levels of the soluble markers did not correlate with each other. CD4 T-cell counts pre-ART tended to modestly correlate with levels of D-dimer (r = 0.35; P = 0.058) and CRP (r = 0.33; P = 0.078). At 36 weeks after treatment interruption (week 72), D-dimer levels returned back to pre-ART levels. However, CD8 T-cell activation was significantly lower than pre-ART levels (35.8% at week 0 vs 28.9% at week 72; P = 0.004). CONCLUSIONS: Among the A5217 participants who started ART within the first 6 months of HIV infection, high levels of sCD14 and CRP remain similar to pre-ART levels, suggesting that immune damage occurring in the initial stages of infection persists despite short-term virologic suppression.
Asunto(s)
Antirretrovirales/uso terapéutico , Biomarcadores/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Inflamación/patología , ADP-Ribosil Ciclasa 1/análisis , Adulto , Coagulación Sanguínea , Proteína C-Reactiva/análisis , Linfocitos T CD4-Positivos/química , Linfocitos T CD8-positivos/química , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Antígenos HLA-DR/análisis , Humanos , Receptores de Lipopolisacáridos/sangre , Activación de Linfocitos , Masculino , Glicoproteínas de Membrana/análisis , Plasma/química , Resultado del TratamientoRESUMEN
Despite the success of combination antiretroviral therapy (cART), a latent viral reservoir persists in HIV-1-infected persons. Unfortunately, endogenous cytotoxic T lymphocytes (CTLs) are unable to control viral rebound when patients are removed from cART. A "kick and kill" strategy has been proposed to eradicate this reservoir, whereby infected T cells are induced to express viral proteins via latency-inducing drugs followed by their elimination by CTLs. It has yet to be determined if stimulation of existing HIV-1-specific CTL will be sufficient, or if new CTLs should be primed from naïve T cells. In this review, we propose that dendritic cells (DCs), the most potent antigen presenting cells, act as dog trainers and can induce T cells (the dogs) to do magnificent tricks. We propose the hypothesis that an HIV-1 cure will require targeting of naïve T cells and will necessitate "teaching new dogs new tricks" while avoiding activation of potentially dysfunctional endogenous memory CTLs (letting the sleeping dogs lie).