Background Early virological response (VR) to enfuvirtide-based salvage regimens at week 12 has been described as a predictor of long-term therapeutic success. The relationship between enfuvirtide ...plasma exposure and VR has not yet been investigated in the clinical setting. Our aim was to investigate the role of enfuvirtide plasma exposure as a determinant of early VR in the clinical setting. Methods Forty-two multidrug-experienced patients starting a salvage enfuvirtide-based regimen were prospectively evaluated over a 12 week period. HIV-RNA levels and enfuvirtide Ctrough were regularly measured. VR was considered as achievement of viral load (VL) undetectability and/or a decrease of more than 1 log at week 12. Results Optimized background score (OBS) and enfuvirtide Ctrough concentrations were associated with VL decrease at week 12. An OBS ≥2 and enfuvirtide Ctrough >2100 ng/mL were associated with VR. The pharmacokinetic/pharmacodynamic (PK/PD) analysis confirmed this exposure–response relationship both in the total population and in different groups according to OBS <2 or ≥2. Higher estimates of IC50 were calculated for the OBS <2 group when compared with the OBS ≥2 group (7551 versus 2330 ng/mL, respectively), without a marked difference in I0 (0.31 versus 0.21 log) and Imax (−2.64 versus −3.33 log). Conclusions Enfuvirtide plasma exposure and OBS were found to significantly influence the magnitude and rate of early VR. The PK/PD modelling of enfuvirtide concentrations was different in our clinical setting, compared with previous data obtained under trial conditions. Therefore, optimization of enfuvirtide plasma exposure could deserve further evaluation as a determinant of therapeutic response in HIV-positive patients.
Abstract Objective: To assess whether the clinical course of HIV infection has changed from 1985 to 1995. Design: Cohort study. Setting: Infectious diseases clinic. Subjects: 285 patients recruited ...from September 1985 to January 1995 with ≤12 months between the dates of their last seronegative and first seropositive test result and with first follow up visit in the six months after seroconversion and at least 12 months' follow up. Patients were grouped according to the date of seroconversion. Main outcome measures: Time to CD4 cell count of <500, 400, and 200 x 106 cells/l and clinical outcome defining AIDS; variation in cell count per day between consecutive visits, and ratio between this variation and time from estimated date of seroconversion at each visit. Results: The groups were similar in age, number with acute primary HIV infection, CD4 cell count at intake, and cell count at the beginning of antiretroviral treatment; they differed in sex ratio, risk factors for HIV, probability of CD4 cell decline to <500, 400, and 200x106 cells/l, and risk of developing AIDS. Acute infection, seroconversion after December 1989, and serum ß2 microglobulin >296 nmol/l were independent predictors of poor clinical course. The speed of CD4 cell decline, expressed as cell variation divided by the number of days between consecutive visits, increased with more recent seroconversion (P=0.02). Ratio between the speed of CD4 cell decline and time from estimated date of seroconversion at each visit was also higher in the patients who seroconverted after December 1989. Conclusions: The faster disease progression and the higher speed of CD4 cell decline at early stages in the patients with recently acquired HIV infection suggest changes in the clinical course of HIV infection. Key messages Interest in possible changes in the course of HIV infection has recently increased Previous research has shown no clear trend for changes in CD4 cell count by interval after HIV seroconversion Results from a large and heterogeneous cohort of patients who seroconverted between September 1985 and January 1995 showed that the patients who seroconverted after December 1989 had a higher probability of decline in CD4 cell count and progression to AIDS than did patients who had seroconverted before this date The overall rate of decline in CD4 cell count was higher in patients who seroconverted after December 1989; 180 days after seroconversion the rate was highest in those who seroconverted after December 1989, and 360 days after seroconversion it was highest in those who seroconverted after December 1989 and before January 1991 Repeated monitoring within the first months after HIV seroconversion is needed to identify those patients who could benefit from early antiretroviral treatment
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To retrospectively determine whether the application of thermal ablation to recurrent and advanced head and neck cancer (HNC) could allow for local tumor control.
From 2002 to 2014, 22 patients (17 ...men and 5 women; mean age, 64 y; age range, 42-88 y) with unresectable HNC lesions treated with thermal ablation were evaluated. Patients were followed at 3 and 6 months after treatment, every 6 months for 5 years, and yearly thereafter with computed tomography and/or magnetic resonance imaging. The mean follow-up period was 32.2 months (range, 3-51 mo).
Three of 22 patients with primary lesions are still alive; two of these patients were treated with radiofrequency (RF) ablation and one was treated with microwave (MW) ablation. Of the 19 remaining patients, four were treated with MW ablation and 15 were treated with RF ablation. Imaging revealed partial response in eight patients, and complete response was observed in the remaining 14. There were two major complications after ablation treatment. The mean survival time was 32.9 months ± 3.205 (standard error; 95% confidence interval CI, 26.6-39.2 mo). The survival time for MW ablation cases (36 mo ± 5.185; 95% CI, 25.8-46.16 mo) was longer than for RF ablation (32.2 mo ± 3.911; 95% CI, 24.5-39.8 mo), although the CI overlap between the groups is large.
Percutaneous thermal ablation is a promising alternative treatment for local control of incurable HNC.
Between march 1994, the seroconversion to HBV associated to the seroconversion to HIV was investigated in 120 HIV seroconverters drawn from 2368 i.v. drug misusers screened for HIV, HBV and STDs. ...Among the 185 individuals susceptible to HIV and HBV at intake (41/120 HIV seroconverters and 144/364 HIV-negative controls), HBV seroconversion was associated with the seroconversion to HIV (p = 0.006) and history of more than 3 sexual partners per year (p = 0.000). Only the history of more than 3 partners per year remained associated with the HBV seroconversion in the conditional regression. The associated seroconversion to HIV and HBV was linked to the short period of i.v. drug injections (p = 0.032), history of more than 3 partners per year (p = 0.000) and more than 3 i.v. drug injections per day (p = 0.016). Compared to the seroconverters to HBV alone, the seroconverters to HBV and HIV were likely to have higher frequency of i.v. drug injection per day on univariate (p = 0.031) and multivariate analysis (p = 0.024). The seroconverters to both the viruses differed from the seroconverters to HIV alone in the year of drug use (p = 0.048). The multivariate analysis confirmed only the association with high frequency of injection per day (p = 0.033). Higher risk of HIV seroconversion from the debut of i.v. drug use was observed in the subjects with concurrent HBV seroconversion (Log-Rank test: p = 0.0008).
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Early treatment in primary HIV infection represents a chance to suppress viral replication both in plasma and in sanctuary sites, and to reconstitute the immune system, at least partly, with a ...theoretical benefit on the natural history of the disease. In order to decide whether to initiate highly aggressive antiretroviral therapy in a patient soon after infection, a physician has to take into account the short- and long-term side-effects of these drugs.
We enrolled 134 newly human immunodeficiency virus type 1 (HIV-1)-infected subjects in a prospective study to determine the natural history of the infection and evaluate the risk of developing AIDS ...after acute primary HIV-1 infection (API). Twenty-three patients were observed during an acute primary HIV-1 infection, and 111 were asymptomatic seroconverters. Acute primary HIV-1 infection was more frequently observed in subjects who had acquired the infection through sexual transmission. Intravenous drug users were rarely affected and presented with milder symptomatology. Patients observed with an acute primary HIV-1 infection had a significantly higher risk of developing AIDS than asymptomatic seroconverters (68% at 56 months vs. 20% at 66 months; p = 0.026). Low CD4+ cell counts at the onset of acute illness and delayed seroconversion in enzyme-linked immunosorbent assay (ELISA) were associated with evolution to AIDS in acute seroconverters (p = 0.03 and 0.02, respectively). During the follow-up, patients with an acute illness were more likely to show an early fall of CD4+ cell counts below 200/microliters than asymptomatic seroconverters. The results of this follow-up study suggest the opportunity to study antiviral treatment protocols in patients with API as a possible measure to control disease progression.
To investigate the relationship between cytokine serum levels, peripheral blood lymphocyte subsets and clinical picture in acute primary HIV-1 infection.
Absolute number/microliters total ...lymphocytes, CD4+, CD8+ and natural killer (NK) cells, as well as serum levels of soluble CD8 receptor, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, beta 2-microglobulin and 5'-neopterin were determined in 15 patients with acute primary HIV-1 infection, 16 asymptomatic HIV-1-seropositive individuals and 18 HIV-1-seronegative individuals at risk for HIV-1 infection.
Acute primary HIV-1 infection was characterized by significant CD4+ lymphocytopenia with low IL-2 serum concentrations, and by high absolute number of circulating CD8+ and NK cells, with elevated serum levels of soluble CD8 receptor, IL-1 beta, IFN-gamma and 5'-neopterin. Follow-up of acute seroconverters showed a significant decrease in NK cell counts and IL-1 beta levels, with an increase of IL-6.
In acute primary HIV-1 infection, significant alteration of cytokine release, possibly induced by viral antigens, could be responsible for both clinical picture and activation of cytotoxic cells through abnormal mechanisms.
Patients were included in the analysis if they had a positive result of an HIV test preceded by a negative result within 12 months, a measurement of their CD4 cell count within six months of their ...positive HIV test result, and at least 12 months' follow up after entry (presumably the estimated date of seroconversion). Because patients infected with HIV often attend clinics only when their immune system is compromised and they begin to experience symptoms, the last of these criteria may have selectively excluded patients with a slower progression of disease and decline in CD4 cell counts from the group of patients who seroconverted more recently. ...the suggestion that only the first year of follow up should be considered implies a reliance primarily on the viral load, which is information that we had for only some of the patients.
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