Guided Internet-delivered cognitive behavioural treatment for insomnia: a randomized trial.

BACKGROUND: Insomnia is a prevalent problem with a high burden of disease (e.g. reduced quality of life, reduced work capacity) and a high co-morbidity with other mental and somatic disorders. Cognitive behavioural therapy (CBT) is effective in the treatment of insomnia but is seldom offered. CBT delivered through the Internet might be a more accessible alternative. In this study we examined the effectiveness of a guided Internet-delivered CBT for adults with insomnia using a randomized controlled trial (RCT). METHOD: A total of 118 patients, recruited from the general population, were randomized to the 6-week guided Internet intervention (n = 59) or to a wait-list control group (n = 59). Patients filled out an online questionnaire and a 7-day sleep diary before (T0) and after (T1) the 6-week period. The intervention group received a follow-up questionnaire 3 months after baseline (T2). RESULTS: Almost three-quarters (72.9%) of the patients completed the whole intervention. Intention-to-treat (ITT) analysis showed that the treatment had statistically significant medium to large effects (p < 0.05; Cohen's d between 0.40 and 1.06), and resulted more often in clinically relevant changes, on all sleep and secondary outcomes with the exception of sleep onset latency (SOL) and number of awakenings (NA). There was a non-significant difference in the reduction in sleep medication between the intervention (a decrease of 6.8%) and control (an increase of 1.8%) groups (p = 0.20). Data on longer-term effects were inconclusive. CONCLUSIONS: This study adds to the growing body of literature that indicates that guided CBT for insomnia can be delivered through the Internet. Patients accept the format and their sleep improves.

Acceptance and tolerability of an adjuvanted nH1N1 vaccine in HIV-infected patients in the Cologne-Bonn cohort.

OBJECTIVE: To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. METHOD: 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg) during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. RESULTS: In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25%) reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%), swelling 96 (20%), redness 54 (11%), fever 48/475 (10%), muscle/joint ache 173 (36%), headache 127 (27%), and fatigue 210 (44%). Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (>50 copies/mL). No correlation was noted for CD4 cell count, age, gender or ethnicity. - In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75%) accepted, while 136 (25%) rejected. Main reasons for rejection were: Negative media coverage (35%), indecisiveness with preference to wait until a later date (23%), influenza not seen as personal threat (19%) and scepticism towards immunization in general (10%). CONCLUSION: A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in the three study centres. No severe adverse events were reported. The tolerability was in most parts comparable to general population. Acceptance rate towards influenza vaccination was high (75%). Those refusing the immunization mentioned negative media coverage as the major influence on their decision.

Transmission of human immunodeficiency virus I drug resistance - a case report. What are the clinical implications?

The success of first-line antiretroviral therapy can be challenged by the acquisition of primary drug resistance. Here we report a case where baseline genotypic resistance testing detected resistance conferring nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-associated mutations, but no primary mutations for protease inhibitor (PI). Subsequent PI-based HAART with boosted saquinavir led to virological treatment success with persistently undetectable viral load. After treatment simplification from saquinavir to an atazanavir based PI-therapy and no change in backbone therapy rapid virological breakthrough occurred. Retrospective analysis displayed preexisting gag cleavage site mutations which may have reduced the genetic barrier in a clinical relevant manner in combination with the already existing NRTI resistance mutations. Alternatively, this effect could be explained with a different antiviral potency for the respective PIs used.

Determination of nevirapine in plasma by GC-MS.

Here we describe a simple, stable, and specific gas chromatography-mass spectrometry (GC-MS) method for the determination of nevirapine in plasma. After precipitation of proteins, the non-nucleoside reverse transcriptase inhibitor nevirapine was extracted with dichloromethane. For the determination and quantification of nevirapine, 1 microL of the organic layer was injected onto the GC-MS system. Linear calibration curves were obtained with BIRH 0414BS as internal standard in a range from 0.01 to 15 microg/mL. Intra- and inter-day accuracy and precision of this method were good with an accuracy between 96-109% and a precision between 2-8% across the therapeutic range of nevirapine. GC-MS proved to be a valid alternative to high-performance liquid chromatography and liquid chromatography-MS.

SEN Virus infection in HIV/HCV coinfected patients.

BACKGROUND: Chronic Hepatitis C Virus (HCV) infection is currently one of the most relevant coinfections in HIV positive patients. The influence of SEN Virus (SENV) on the outcome of HCV therapy in HIV/HCV coinfected patients who underwent combination therapy with pegylated interferon (PEG-IFN) and ribavirin is unclear. METHODS: SENV DNA was determined by polymerase chain reaction in 67 HIV/HCV coinfected patients, 77 HIV monoinfected patients, 95 treatment naive HCV monoinfetcted patients, and 122 healthy blood donors. Quantitative analysis was done for SENV H DNA. RESULTS: SENV DNA was detected in 8 of 67 (12%) HIV/HCV coinfected patients, in 9 of 77 (11.7%) HIV monoinfected patients, in 21 of 95 (22%) HCV monoinfected patients, and 12 of 122 (9.8%) healthy blood donors. HIV monoinfected patients showed the highest mean SENV H DNA level. The mean SENV H DNA was significantly lower in HIV/HCV coinfected patients compared to all other groups. The sustained virological response rates to combination therapy of HCV in HIV/HCV coinfected patients did not differ between patients with detectable SENV 5/8 (62.5%) and without SENV 28/59 (47.5%; p = 0.47). We found no significant difference in SENV H DNA pretreatment levels between nonresponders and responders to combination therapy (112 +/- 144 copies vs. 8 +/- 7 copies/ml; p = 0.27). CONCLUSION: Coinfection with HCV may reduce SENV H replication in HIV positive patients and results in significantly lower SENV H DNA levels in HIV/HCV coinfected patients. SENV infection has no influence on the outcome of HCV combination therapy in HIV/HCV coinfected patients.

CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature.

In the context of emerging resistance to antiretroviral agents in HIV medicine, the development of new drugs classes with a novel mechanism of action remains essential. The CCR5 co-receptor antagonists inhibit fusion of HIV with the host cell by blocking the interaction between the gp-120 viral glycoprotein and the CCR5 chemokine receptor. So far, four CCR5 antagonists have entered clinical evaluation, of which three are currently still in different stages of clinical assessment. In this review we compare the clinical efficacy in phase I and II as well as the long-term tolerability, pharmacokinetics and interactions of these new antiretroviral drugs entering HIV practice. Being the first CCR5 antagonist to be investigated in clinical trials, aplaviroc showed initial potent antiviral activity. However, after the occurrence of severe hepatotoxicity in several patients, its development had to be stopped in October 2005. The second CCR5 antagonist, maraviroc, has displayed promising results in phase I, II and III studies, showing a significantly greater decline in HIV RNA and CD4 cell increase compared to placebo, with no clinically relevant differences in safety profile and tolerability. The expanded access program for maraviroc was opened in June 2007 in several European countries. The FDA approved the use of maraviroc for antiretroviral therapy of HIV on the 7th of august, 2007. Finally, the third CCR5 antagonist vicriviroc also showed long-term potent viral activity in phase II studies as long as it was boosted with low-dose ritonavir, with no significant differences in grade 3 and grade 4 adverse effects compared to placebo. The phase II clinical trial amongst ART experienced individuals who received Ritonavir-boosted vicriviroc 10-15 mg qd was unblinded early because of the unexpected occurrence of malignant lymphoma and adenoma. However, no further malignancies occurred in the extended follow-up evaluation of this drug until today. Vicriviroc is currently entering phase III evaluation. Pharmacokinetics of maraviroc and vicriviroc may be influenced by coadministration of CYP3A4-inhibitors and -inducers, since both substances are metabolised primarily by the CYP3A4 system. This requires dose adjustments when combined with for instance protease inhibitors (with the exception of tipranavir/r), efavirenz, ketoconazole or rifampin. Concerns have risen about possible class-specific long-term adverse effects of CCR5 antagonists, particularly with regard to hepatotoxicity or malignancy. The pooled data from phase II and III however, so far show no new or added toxicity risk for maraviroc or vicriviroc compared to the respective placebo arms of the trials. Extended follow-up of the vicriviroc trials showed no further case of malignancy, reassuring the overall good tolerability profile of the drug so far.

The relation between coping, social support and psychological and somatic symptoms among torture survivors in Nepal.

BACKGROUND: Little is known about the relation between coping, social support, and psychological and somatic symptoms among survivors of torture living outside the West. METHOD: In a population-based dataset of 315 tortured Bhutanese refugees, univariate and multivariate relationships between coping and social support and symptoms were estimated. These relationships were verified in a second sample of 57 help-seeking Nepalese torture survivors. RESULTS: A relationship was observed between the total number of coping strategies used and anxiety and depression. Negative coping, in contrast to positive coping, was related to all symptom outcome measures. Received social support was stronger related to symptoms than perceived social support. The findings from the first sample were replicated in the second sample. CONCLUSION: We found hypothesized relationships between coping, social support, and psychological and somatic symptoms among survivors of torture living in Nepal. The findings from this study confirm the importance of understanding specific types of coping and social support to develop intervention programmes for torture survivors in Non-western settings.