METHODS: PubMed, LILACS and Google Scholar were searched for randomized or non-randomized trials enrolling patients with suspected or confirmed dengue where CP extract was compared, as a treatment measure, against standard treatment. Recovery of platelet counts as well as other clinical indicators of favourable outcome (duration of hospital stay, prevention of plasma leakage, life threatening complications, and mortality) were assessed.
RESULTS: Nine studies (India-6, Pakistan-1, Indonesia-1, Malaysia-1) met the inclusion criteria. Seven studies showed an increase in platelet counts in patients receiving CP extract, while one study showed no significant difference between the two groups, and direct comparison was not possible in the remaining study. Serious adverse events were not reported. CP extract may reduce the duration of hospital stay (mean difference - 1.98 days, 95% confidence interval - 1.83 to - 2.12, 3 studies, 580 participants, low quality evidence), and cause improvement in mean platelet counts between the first and fifth day of treatment (mean difference 35.45, 95% confidence interval 23.74 to 47.15, 3 studies, 129 participants, low quality evidence). No evidence was available regarding other clinical outcomes.
CONCLUSIONS: The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome. Current evidence is insufficient to comment on the role of CP extract in dengue. There is a need for further well designed clinical trials examining the effect of CP on platelet counts, plasma leakage, other serious manifestations of dengue, and mortality, with clearly defined outcome measures.
METHODS: Five graph models were fit using data from 1574 people who inject drugs in Hartford, CT, USA. We used a degree-corrected stochastic block model, based on goodness-of-fit, to model networks of injection drug users. We simulated transmission of HCV and HIV through this network with varying levels of HCV treatment coverage (0%, 3%, 6%, 12%, or 24%) and varying baseline HCV prevalence in people who inject drugs (30%, 60%, 75%, or 85%). We compared the effectiveness of seven treatment-as-prevention strategies on reducing HCV prevalence over 10 years and 20 years versus no treatment. The strategies consisted of treatment assigned to either a randomly chosen individual who injects drugs or to an individual with the highest number of injection partners. Additional strategies explored the effects of treating either none, half, or all of the injection partners of the selected individual, as well as a strategy based on respondent-driven recruitment into treatment.
FINDINGS: Our model estimates show that at the highest baseline HCV prevalence in people who inject drugs (85%), expansion of treatment coverage does not substantially reduce HCV prevalence for any treatment-as-prevention strategy. However, when baseline HCV prevalence is 60% or lower, treating more than 120 (12%) individuals per 1000 people who inject drugs per year would probably eliminate HCV within 10 years. On average, assigning treatment randomly to individuals who inject drugs is better than targeting individuals with the most injection partners. Treatment-as-prevention strategies that treat additional network members are among the best performing strategies and can enhance less effective strategies that target the degree (ie, the highest number of injection partners) within the network.
INTERPRETATION: Successful HCV treatment as prevention should incorporate the baseline HCV prevalence and will achieve the greatest benefit when coverage is sufficiently expanded.
FUNDING: National Institute on Drug Abuse.
METHODS: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012.
RESULTS: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%.
CONCLUSIONS: In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some "real world" data.