Ioana Bica

Increasing Mortality Due to End-Stage Liver Disease in Patients with Human Immunodeficiency Virus Infection

Highly active antiretroviral therapy has decreased human immunodeficiency virus (HIV)-associated mortality; other comorbidities, such as chronic liver disease, are assuming greater importance. We retrospectively examined the causes of death of HIV-seropositive patients at our institution in 1991, 1996, and 1998-1999. In 1998-1999, 11 (50%) of 22 deaths were due to end-stage liver disease, compared with 3 (11.5%) of 26 in 1991 and 5 (13.9%) of 36 in 1996 (P=.003). In 1998-1999, 55% of patients had nondetectable plasma HIV RNA levels and/or CD4 cell counts of >200 cells/mm(3) within the year before death. Most of the patients that were tested had detectable antibodies to hepatitis C virus (75% of patients who died in 1991, 57.7% who died in 1996, and 93.8% who died in 1998-1999; P=NS). In 1998-1999, 7 patients (31.8%) discontinued antiretroviral therapy because of hepatotoxicity, compared with 0 in 1991 and 2 (5.6%) in 1996. End-stage liver disease is now the leading cause of death in our hospitalized HIV-seropositive population.

Daptomycin-Resistant, Methicillin-Resistant Staphylococcus aureus Bacteremia

We describe a patient who developed daptomycin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) during an episode of presumed septic thrombophlebitis of the portal vein. Although daptomycin is an alternative agent for treatment of drug-resistant gram-positive bacterial infections, development of resistance during prolonged use may occur with MRSA bacteremia from a persistent focus.

Use of Complementary and Alternative Therapies by Patients With Human Immunodeficiency Virus Disease in the Era of Highly Active Antiretroviral Therapy

BACKGROUND Complementary and alternative medical therapies (CAM) are popular with patients who are human immunodeficiency virus (HIV) seropositive, despite effective drug treatments, potential drug interactions, and overlapping toxicities. OBJECTIVE To determine rates and correlates of ingested and noningested CAM use, and to examine temporal changes in the rates of ingested CAM use during the introduction of highly active antiretroviral therapy (HAART). DESIGN Cross-sectional analysis with repeated measures from a cohort study, with the study visit as the unit of analysis. SETTING Eastern Massachusetts and Rhode Island. PARTICIPANTS Adults who are HIV seropositive followed semiannually (n = 642) in Nutrition for Healthy Living (NFHL) study. MEASUREMENTS Rates of ingested and noningested CAM use were assessed by interview every 6 months between 1995 and 1999. RESULTS Ingested CAM use was reported at 60% of visits. Between 1995 and 1999, HAART use increased from 0% to 70%, and ingested CAM use decreased from 71% to 52%. In multivariate analyses, users of ingested complementary therapies were more likely to be gay men (prevalence ratio [PR] 1.40, 95% confidence interval [CI] 1.23-1.58; p < 0.0001), at least high school educated (PR 1.37, 95% CI 1.12-1.68, p = 0.002), and with secure housing (PR 0.75, 95% CI 0.61-0.92; p = 0.007). Even in the lowest risk group (less educated, nongay males with insecure housing), CAM use rates were 27% (95% CI 21%-34%). There was no association between HAART and CAM use. CONCLUSIONS CAM therapies complement, rather than replace, HAART. Even among poorly educated, nongay male patients with insecure housing, rates of ingested CAM use were substantial. Physicians should routinely ask about ingested CAM therapy use and become knowledgeable about potential hazards.

Acute Hepatitis C Virus Infection in Incarcerated Injection Drug Users

BACKGROUND The Centers for Disease Control and Prevention has emphasized the need for interventional programs regarding hepatitis C virus (HCV) infection for injection drug users, the group of persons who are at highest risk of acquiring acute infection. METHODS We designed a pilot study to assess the feasibility of identifying injection drug users with acute HCV infection in correctional and detoxification facilities. On-site medical providers were educated regarding risk factors and signs and symptoms of infection and were instructed to refer all patients with hepatitis to our specialty clinic. RESULTS Over a 30-month period, 21 patients received a diagnosis of acute hepatitis C, 3 received a diagnosis of hepatitis B, and 1 received a diagnosis of hepatitis A. Of the 21 patients with acute hepatitis C, 19 were identified in the prison setting shortly after incarceration. Of the 17 patients who were observed serially (mean duration of observation, 6.3 months), 8 had spontaneous virologic clearance. Early therapy with pegylated interferon was initiated for 5 patients with persistent viremia and led to a sustained virologic response in 2 individuals. All patients agreed to undergo human immunodeficiency virus counseling and testing, as well as to receive immunization for hepatitis A and B. CONCLUSIONS Incarceration presents a unique opportunity to identify injection drug users with acute HCV infection, to initiate counseling regarding other bloodborne pathogens, and to facilitate immunizations and HCV treatment.

Metabolic Syndrome Predicts All-Cause Mortality in Persons with Human Immunodeficiency Virus

We examined the association between metabolic syndrome (MS) and its individual defining criteria on all-cause mortality in human immunodeficiency virus (HIV)-infected persons. We used data from 567 HIV-infected participants of the Nutrition for Healthy Living study with study visits between 9/1/2000 and 1/31/2004 and determined mortality through 12/31/2006. MS was defined using modified National Cholesterol Education Program guidelines. Cox proportional hazards for all-cause mortality were estimated for baseline MS status and for its individual defining criteria. There were 83 deaths with median follow-up of 63 months. Baseline characteristics associated with increased risk of mortality were: older age in years (univariate hazard ratio [HR] 1.04, p<0.01), current smoking (HR 1.99, p=0.02), current heroin use (HR 1.97, p=0.02), living in poverty (HR 2.0, p<0.01), higher mean HIV viral load (HR 1.81, p<0.01), and having a BMI <18 (HR 5.84, p<0.01). For MS and its criteria, only low HDL was associated with increased risk of mortality on univariate analysis (HR 1.84, p=0.01). However, metabolic syndrome (adjusted HR 2.31, p=0.02) and high triglycerides (adjusted HR 3.97, p<0.01) were significantly associated with mortality beyond 36 months follow-up. MS, low HDL, and high triglycerides are associated with an increased risk of mortality in HIV-infected individuals.

Delivering Therapy for Hepatitis C Virus Infection to Incarcerated HIV-Seropositive Patients

The increase in morbidity and mortality due to end-stage liver disease has fueled recent guidelines that recommend consideration of treatment for hepatitis C in human immunodeficiency virus (HIV)-infected patients. Unfortunately, studies indicate that few patients coinfected with HIV and hepatitis C virus (HCV) are treated for their underlying hepatitis because of ongoing substance abuse, depression, chaotic lifestyles, homelessness, and perceived nonadherence. The structured environment of the prison system enables clinicians to provide complicated therapies for HCV to HIV-infected patients in combination with substance abuse programs. Furthermore, adherence to and adverse effects of therapy can be closely monitored. Offering treatment for HCV infection during incarceration to HIV-seropositive persons is highly efficient and targets underserved minority patients who have limited access to care in the community.

Difficulty Swallowing and Lack of Receipt of Highly Active Antiretroviral Therapy Predict Acute Weight Loss in Human Immunodeficiency Virus Disease

In human immunodeficiency virus (HIV) disease, symptoms of underlying illness may promote weight loss through decreased caloric intake, increased metabolic needs, or nutrient malabsorption. We evaluated disease symptoms as predictors of acute weight loss (i.e., loss of > or =5% of weight). HIV-infected men and women (n=415) were telephoned every 5 weeks to obtain information about weight and recent symptoms. Weight change between each pair of consecutive calls (telephone intervals, 2814) was calculated. Acute weight loss occurred across 4.5% of intervals and among 24% of individuals. Patients reported > or =1 symptom before 58% of telephone intervals. The most common symptoms or symptom complexes before intervals were diarrhea (21% of patients), anorexia (17%), upper respiratory symptoms (16%), skin symptoms (12%), and abdominal pain (12%). Trouble swallowing (6%) and oral symptoms (7%) were less common. Risk of acute weight loss was significantly increased when oral symptoms or trouble swallowing were present, and it was decreased when highly active antiretroviral therapy (HAART) was used or when diarrhea was not present. Even when HAART is being administered, clinicians should remain vigilant regarding weight loss, oral symptoms, and trouble swallowing.

Managing Symptomatic Drug-Induced Liver Injury in HIV—Hepatitis C Virus—Coinfected Patients: A Role for Interferon

BACKGROUND Human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV) coinfection are at increased risk for drug-induced liver injury (DILI) compared with patients with HIV infection alone. The mechanism underlying this observation is unknown. We hypothesized that interferon (IFN) would induce biochemical improvement through its anti-inflammatory properties and thereby facilitate the reintroduction of antiretroviral therapy (ART) in patients with DILI. METHODS Patients with symptomatic DILI were referred for evaluation; biopsy of a liver sample was performed for all patients, except 1 with clinical cirrhosis. RESULTS Twelve patients with acquired immunodeficiency syndrome and symptomatic grade 3/4 hepatotoxicity received treatment with IFN and ribavirin (RBV). Seven of these patients had a history of recurrent DILI. The mean baseline CD4(+) T cell counts and HIV RNA levels were 124 cells/mm(3) and 115,369 copies/mL, respectively. Biopsies of liver samples demonstrated significant necroinflammation (mean grade, 10.3) and fibrosis (mean stage, 2.9). Three patients continued to receive ART when they began treatment with IFN-RBV; 9 reinitiated ART within an average of 12 weeks (range, 4-20 weeks) of HCV treatment initiation. All patients attained marked improvement in aminotransferases and continued to receive ART treatment during a mean follow-up regimen of 26.5 months, with subsequent virologic suppression and immunologic reconstitution (mean CD4(+) cell count increase, 251/mm(3)). However, only 1 patient maintained HCV suppression after completion of treatment with IFN-RBV. CONCLUSIONS In patients with symptomatic DILI, treatment with IFN-ribavirin (RBV) led to decreases in aminotransferase levels, which enabled the reinitiation of ART. The beneficial effects of IFN-based therapy may be modulated through the suppression of proinflammatory cytokines, even in virologic nonresponders. Herein, we propose a novel mechanism for DILI, whereby HCV- and HIV-associated inflammatory mediators induce liver injury synergistically.