Impact of hepatitis C virus coinfection on response to highly active antiretroviral therapy and outcome in HIV-infected individuals: A Nationwide Cohort Study
ABSTRACT Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among Danish patients with HIV-1 infection.
This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR results [443 patients [16%]]), HCV negative (consistent negative HCV serological test results [2183 patients [80%]]) and HCV-U (never tested for HCV [108 patients [4%]]). The study end points were viral load, CD4+ cell count, and mortality.
Compared with the HCV-negative group, overall mortality was significantly higher in the HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9-3.0), as was liver disease-related mortality (mortality rate ratio, 16; 95% CI, 7.2-33). Furthermore, patients in the HCV-positive group had a higher risk of dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count.
HIV-HCV-coinfected patients are compromised in their response to highly active antiretroviral therapy. Overall mortality, as well as mortality from liver-related and acquired immunodeficiency syndrome-related causes, is significantly increased in this patient group.
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ABSTRACT: Survival among HIV-infected patients markedly improved with the introduction of highly active antiretroviral therapy (HAART). Easier to take and more effective HAART options have improved the one-year virologic success rate among naive patients. Numerous studies have shown that initiating HAART and restoration of CD4 cells positively impact survival. There are only a few evaluations that have been carried out on the changes in survival among patients who are severely immunosuppressed. We evaluated survival among a cohort of veterans with CD4<100 cells/mm(3) (CD4 < 100) in three time periods reflecting early, mid, and recent HAART. Using the HIV clinic database, all patients with CD4 < 100 seen between 1996 and 2004 were identified (n=394). Patients entered Cohorts 1 (n=219), 2 (n=72), and 3 (n=103) in 1996-1998, 1999-2001, and 2002-2004, respectively. Data on demographics, AIDS-defining illnesses, co-morbidities, treatment, CD4, and viral load (VL) were abstracted. Survival analysis controlling for the above variables was performed and odds ratios with 95% confidence intervals were calculated. Rate of virologic suppression was higher for Cohort 2 when compared to Cohort 1 (63% vs. 46%, p<0.05), but lower for Cohort 3 when compared to Cohort 2 (49%, p<0.05). Survival at one year was high for Cohorts 1 and 2 (92-95%), but significantly lower in Cohort 3 (80%). On logistic regression analysis and for the whole cohort, HAART use, achieving a CD4 > 200 and VL<400 were independent predictors of survival. Older age at cohort entry and having a diagnosis of lymphoma, Mycobacterium avium complex infection, coronary artery disease, or renal insufficiency were negative predictors. In the most recent HAART period 2002-2004, one year survival after CD4 < 100 significantly decreased in spite of availability of specialized HIV clinical and support services and antiretrovirals. Our results suggest that more than better drugs are needed for improving survival among certain patient populations with advanced immunosuppression.AIDS Care 07/2010; 22(7):886-94. DOI:10.1080/09540120903499162 · 1.60 Impact Factor
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ABSTRACT: Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference -46.0 cells/microL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population.Alcoholism Clinical and Experimental Research 05/2007; 31(5):829-36. DOI:10.1111/j.1530-0277.2007.00381.x · 3.31 Impact Factor
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ABSTRACT: A large number of transmission transactions is expected to take place with the introduction of competition into the electricity industry. These transactions need to be evaluated ahead of their scheduling time to check their feasibility with regard to the system conditions at the time of scheduling. Transmission system operators would have to honor and execute only transactions as far as the system design and system operating conditions permit. This paper describes a method for determining the available transfer capability (ATC) between any two locations in transmission system (single-area or multi-area) under a given set of system operating conditions. The method is then used to assess the feasibility of simultaneous bilateral transactions with regard to the system economic dispatch and transmission system constraints. Transactions will be classified into feasible and infeasible. Feasible transactions can be accommodated without violating the system economic dispatch and transmission network constraints. Infeasible transactions violate transmission network constraints and cannot be accommodated fully without altering the system economic dispatch. The assessment method provides information on where and how much generation is to be rescheduled in order to accommodate an infeasible transaction. Such information will be useful in deciding whether a particular infeasible transaction is worth serving or not. The IEEE Reliability Test System is used to illustrate the assessment method.Power Engineering Society 1999 Winter Meeting, IEEE; 01/1999