Faculty Bibliography

OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis. DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU

The current recommendation for the duration of treatment of patients infected with chronic hepatitis C virus (HCV) genotype 1 is 48 weeks; however, the standard regimen of peginterferon plus ribavirin bears significant adverse effects, which make completion of treatment exceedingly difficult. Reported here are 2 cases of HIV-HCV-coinfected genotype-1 patients who discontinued treatment early (after 3 and 8 weeks) because of adverse effects yet had a sustained virologic response with undetectable HCV viral loads at follow-up

Coinfection of hepatitis C virus (HCV), hepatitis B virus (HBV), and HIV is common due to shared modes of transmission. These coinfections accelerate the course of chronic liver disease and facilitate progression to cirrhosis and hepatocellular carcinoma. The viral interactions between these viruses are complex, and their treatment may be challenging for clinicians

The life expectancy of HIV seropositive persons is approaching the life expectancy of those who are uninfected with HIV. Hepatitis C virus (HCV) infection has emerged as a worldwide epidemic. Given the similar transmission route between HCV and HIV, there has been an explosion in the number of individuals infected with both viruses. Because of the successful introduction of antiretroviral therapy, patients are more susceptible to new opportunistic infections such as HCV. HCV leads to a more rapid progression to end-stage liver disease in patients with HIV, and the morbidity and mortality related to HCV in co-infected patients is on the rise. Therefore, it has become imperative to treat both HIV and HCV in co-infected patients. The primary goal of HCV therapy is permanent eradication of the virus. Secondary goals include reduction in hepatic fibrosis progression, development of decompensated cirrhosis, and hepatocellular carcinoma. Early studies using standard interferon-alfa for the treatment of HCV in co-infected individuals were discouraging, as poor outcomes, high discontinuation rates, and severe adverse events were observed. The current standard of care for treatment of HCV is pegylated-interferon and ribavirin. New studies have recently demonstrated a higher sustained virologic response rate and a better adverse event profile than previously reported in co-infected patients. As a result, we recommend considering all co-infected patients for HCV therapy while watching closely for unique treatment-related toxicities. The treatment of HCV in co-infected patients should be a high priority for all providers

Because the life expectancy of patients infected with HIV has been prolonged, liver diseases have assumed far greater importance as a cause of morbidity and mortality in these patients. Given the shared risks of transmission, patients who have HIV often are coinfected with hepatotrophic viruses such as hepatitis C and hepatitis B. Further, antiretroviral therapy (ART) used by patients who have HIV is often hepatotoxic, contributing to liver damage. With increasing immunosuppression caused by AIDS, patients who have HIV have to deal with these issues and the increased risk of infection with opportunistic viral, fungal, bacterial, and protozoal pathogens. In addition, steatosis and lipodystrophy now are recognized more commonly in patients who have HIV, particularly in the setting of ART. Thus, understanding of liver diseases in the setting of HIV infection becomes an important focus in caring these individuals. There have been numerous advances in the treatment of liver disease in patients who have HIV, particularly in treating viral hepatitis C and B. This article reviews various liver manifestations in patients who have HIV and the recent advances in diagnostic and therapeutic options

OBJECTIVES: This study assessed the rates and course of depressive symptomatology and neurocognitive deficits in hepatitis C virus (HCV) patients undergoing interferon treatment, and explored possible predictors of depression and neurocognitive deficits. DESIGN: In order to obtain objective assessments of depression, and to evaluate cognitive impairment, a 72-week prospective study, comprising 48 weeks of treatment and 24 weeks of post-treatment follow-up was utilized. METHODS: A total of 50 HCV patients were assessed at baseline, and 14 times during pegylated interferon plus ribavirin treatment. Patients were also assessed on four timepoints after the termination of treatment. All patients have previously been treated for hepatitis C infection with interferon and were judged to be treatment resistant in these treatments. Depression was assessed using the Center for Epidemiological Studies Depression (CES-D) questionnaire, and patients were interviewed regarding problems with memory, attention and concentration. RESULTS: Eighty-two per cent of interferon-treated patients developed severe enough depressive symptoms to meet the CES-D criteria for possible major depressive disorder (MDD). Possible MDD onset was most frequent by the first week of treatment, and almost all possible MDD cases were observed by week 8. More severe depressive symptoms at baseline were associated with higher depressive symptoms during interferon treatment. Thirty per cent of patients complained about cognitive problems. In half of these patients cognitive impairments were still reported after the termination of treatment. There was no association between depression during interferon treatment and subjective cognitive complaints. CONCLUSIONS: The findings suggest that depression and cognitive impairments are frequent and persistent side-effects of interferon treatment in treatment-resistant patients

BACKGROUND: Survival in HIV infection has improved dramatically in the last decade due to antiretroviral therapy (ART). Due to shared routes of transmission, HCV is found in approximately 30% of HIV infected patients. HCV infection has emerged as a major issue in this population as manifest by a major increase in liver-related mortality. ART-associated hepatotoxicity has been demonstrated to occur more frequently in co-infected individuals and may be severe or fatal in some instances. Thus treatment of HCV has become a priority in HIV infected individuals. OBJECTIVES: The main aims of this review are to summarise and illustrate the current evidence based management of anti-HCV therapy in HIV-infected patients. METHODS: A systematic review of the literature was performed using Pubmed and Medline searches. CONCLUSION: All HIV-infected patients should be screened for HCV infection via anti-HCV antibody and HCV RNA polymerase chain reaction. If HCV infection is present, treatment should be considered in those patients with evidence of liver inflammation and fibrosis. Recent studies have demonstrated the safety and efficacy of anti-HCV therapy in HIV-infected individuals with pegylated interferon and ribavirin combination therapy. HCV genotype is predictive of response to therapy and increasing the duration of therapy to 48 weeks has proven to be more effective in patients with genotypes 2 and 3. HCV treatment with interferon based therapy is associated with many unique side effects and toxicities in this population of which the clinician must be aware