Nina Singh

Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus : prospective assessment with implications for enhancing compliance

Non-compliance with therapy is a significant problem, particularly when the disease process is chronic and therapeutic regimens are employed for prolonged periods. We assessed the prevalence and variables associated with compliance with antiretroviral therapy in patients with human immunodeficiency virus infection, by means of a longitudinal observational study of 46 patients aged 23 to 68 years, with human immunodeficiency virus infection, followed at the Pittsburgh VA Medical Center. Data on demographics, medical status, physical functioning (Karnofsky performance scores), CD4 lymphocyte count, depression (Beck depression inventory), coping (inventory of coping with illness scale scores), and psychological and emotional stress (profile of mood states scale scores), were prospectively assessed on all patients at baseline and every 6 months. Compliance was assessed at 6 and 12 months: patients taking > or = 80% of antiretroviral therapy were considered compliant. Overall, 63% of patients were compliant with antiretroviral therapy. Age, education, employment, religious support, and perceived quality of life did not correlate with compliance. By univariate analysis, lack of prior intravenous drug use was significantly associated with compliance (p = 0.01). Compliant patients had significantly better adaptive coping (p = 0.03), and less depression (p = 0.04). By multivariate analysis, black race was significantly associated with non-compliance independent of intravenous drug use and educational status. History of prior opportunistic infection (which presumably heightens the perceived severity of illness) (p = 0.02), and lesser psychological disturbance scores (p = 0.02) were associated with compliance. Compliance was observed despite the greater number of prescription medications taken by compliant patients (p = 0.04). At 12 months, Karnofsky scores were better in compliant patients (p = 0.02), although mortality was not different. Besides identifying predictors of compliance, our data suggest that symptoms of depression and psychological stress be sought in patients with non-adherence.

Mycobacterium tuberculosis Infection in Solid-Organ Transplant Recipients: Impact and Implications for Management

Tuberculosis is a serious opportunistic infection in transplant recipients. On the basis of the compilation of published reports in the literature, the incidence of Mycobacterium tuberculosis infection in organ transplant recipients worldwide ranged from 0.35% to 15%. Nonrenal transplantation (P = .004), rejection within 6 months before the onset of tuberculosis (P = .02) and type of primary immunosuppressive regimen (P = .007) were predictors of M. tuberculosis infection occurring within 12 months after transplantation. Thirty-three percent (155) of 476 transplant patients with tuberculosis had disseminated infection; receipt of OKT3 or anti-T cell antibodies (P = .005) was a significant predictor of disseminated tuberculosis. Overall, the mortality rate among 499 patients was 29%; disseminated infection (P = .0003), prior rejection (P = .006), and receipt of OKT3 or anti-T cell antibodies (P = .0013) were significant predictors of mortality in patients with tuberculosis. Clinically significant hepatotoxicity due to isoniazid occurred in 2.5%, 4.5%, and 41% of renal, heart and lung, and liver transplant recipients, respectively. The diagnosis and effective management of tuberculosis after transplantation warrant recognition of the unique epidemiological and clinical characteristics of tuberculosis in transplant recipients.

Invasive aspergillosis in transplant recipients

Infections and rejection have long been the leading causes of morbidity and mortality in transplant recipients. Although recent advances in immunosuppression, prophylaxis, and treatment of infections such as cytomegalovirus have resulted in improved outcome in transplant recipients, invasive aspergillosis remains a scourge of transplantation medicine. Invasive aspergillosis has a mortality in this patient population of up to 90% and accounts for 10%-15% of all deaths of transplant recipients in the first year after transplant. Of more than 20,000 transplant recipients who have been reported, incidence of invasive aspergillosis has ranged from 0.7% in kidney transplant recipients to 8.4% in lung transplant recipients. Definite risk factors for development of invasive aspergillosis exist, including delayed engraftment and severe graft-versus-host disease in bone marrow transplant recipients and poor graft function, cytomegalovirus infection, and renal failure in solid-organ transplant recipients. Although a number of prophylactic regimens are in widespread use, none has been shown conclusively to reduce the incidence of invasive aspergillosis. Reducing environmental exposure to Aspergillus, early diagnosis of the infection by means of antigen detection in serum, and use of high-resolution computed tomography are alternatives to use of prophylaxis but have not been systematically evaluated. New treatment options include early surgical intervention in cases of localized disease; lipid preparations of amphotericin, itraconazole, or voriconazole; and immunotherapy with G-CSF or GM-CSF and interferon-gamma.

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

Background. The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. Methods. Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. Results. Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30–1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12–0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16–0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. Conclusions. Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Opportunistic Mycelial Fungal Infections in Organ Transplant Recipients: Emerging Importance of Non-Aspergillus Mycelial Fungi

To determine the spectrum and impact of mycelial fungal infections, particularly those due to non-Aspergillus molds, 53 liver and heart transplant recipients with invasive mycelial infections were prospectively identified in a multicenter study. Invasive mycelial infections were due to Aspergillus species in 69.8% of patients, to non-Aspergillus hyalohyphomycetes in 9.4%, to phaeohyphomycetes in 9.4%, to zygomycetes in 5.7%, and to other causes in 5.7%. Infections due to mycelial fungi other than Aspergillus species were significantly more likely to be associated with disseminated (P=.005) and central nervous system (P=.07) infection than were those due to Aspergillus species. Overall mortality at 90 days was 54.7%. The associated mortality rate was 100% for zygomycosis, 80% for non-Aspergillus hyalohyphomycosis, 54% for aspergillosis, and 20% for phaeohyphomycosis. Thus, non-Aspergillus molds have emerged as significant pathogens in organ transplant recipients. These molds are more likely to be associated with disseminated infections and to be associated with poorer outcomes than is aspergillosis.

Infections Due to Scedosporium apiospermum and Scedosporium prolificans in Transplant Recipients: Clinical Characteristics and Impact of Antifungal Agent Therapy on Outcome

BACKGROUND Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients. METHODS The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Maranon [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non-transplant recipients with scedosporiosis who were described in the literature. RESULTS Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P=.045), to have an earlier onset of infection (P=.007), to be neutropenic (P<.0001), and to have fungemia (P=.04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P=.002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P=.08). Presence of disseminated infection (OR, 0.20; P=.03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P=.02) independently predicted a better survival in this model. CONCLUSIONS Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

Trends in the Epidemiology of Opportunistic Fungal Infections: Predisposing Factors and the Impact of Antimicrobial Use Practices

In the past decade, the frequency of opportunistic fungal infections has increased, and the spectrum of fungal pathogens has changed. The increasing number of susceptible hosts, the introduction of newer modalities for hematopoietic stem cell transplantation, the evolution of organ transplantation practices, the use of novel immunosuppressive agents, and current antimicrobial prophylactic strategies have likely contributed to the changing epidemiology of invasive mycoses. The introduction of azoles more than a decade ago has had a profound impact on curtailing candidal infections. However, a dramatic increase in azole-resistant Candida species and mold infections has been documented. The trends in time of onset, spectrum, and frequency of infections due to invasive molds and opportunistic yeasts are unique for different fungi and vary between subsets of immunocompromised hosts. This review discusses the implications of these trends for guiding judicious use of antimicrobial prophylactics and for unraveling the pathophysiological basis of fungal infections.

Adherence of human immunodeficiency virus-infected patients to antiretroviral therapy.

The impact of demographic, psychosocial, and medical regimen-related variables on adherence of 123 human immunodeficiency virus (HIV)-infected patients to antiretroviral therapy was assessed by means of refill methodology. Satisfaction with social support (P = .029), problem-focused coping (P = .027), and active-behavioral coping (P = .011) correlated significantly with adherence, whereas loss of motivation (P = .006), hopelessness (P = .16), and avoidant coping (p = .015) correlated with nonadherence. At the 6-month follow-up, the mean CD4 cell count differed significantly among adherent versus nonadherent patients (a mean increase of 78/mm3 vs. a mean decrease of 5/mm3; P = .018). Adherence did not correlate with the number of antiretroviral medications consumed per day (mean, 3.0 vs. 2.5). Non-Caucasian patients were more likely to be nonadherent than Caucasian patients (relative risk, 2.5; 95% confidence interval, 1.2-5.3; P = .013); this difference was not explained by age, education, employment, income, history of intravenous drug use, or medical regimen. Non-Caucasian patients, however, were less satisfied with their social support (P = .04) and informational support (P = .016) and were more likely to utilize emotion-focused coping (P = .01). Thus, satisfaction with social support and coping style significantly impacted adherence and likely accounted for the observed racial difference in adherence among HIV-infected patients.

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management

BACKGROUND Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.

Quality of life in patients with human immunodeficiency virus infection: impact of social support, coping style and hopelessness.

We aimed to determine whether the quality of life (QOL) in the patients infected with human immunodeficiency virus (HIV) infection was influenced by satisfaction with social support, coping style and hopelessness. One hundred and thirty-eight HIV-infected patients were prospectively studied in this multicentre, longitudinal study. The QOL was assessed by Medical Outcome Study Health Survey SF-36, social support by Sarason Social Support Questionnaire, hopelessness by Beck Hopelessness Scale, and coping by Billing and Moos Inventory of coping with illness. The QOL did not correlate with age, sex, race, HIV risk factor, education or marital status. Employment (P = 0.0001), higher income (P = 0.03), satisfaction with social support (P = 0.04), regardless of the source of that support, and problem-focused coping (P = 0.03) were associated with a significantly better QOL, while, emotion-focused coping (r = -0.19, P = 0.04), avoidant coping (r = 0.40, P = 0.0001), hopelessness (r = -0.64, P = 0.0001) and AIDS (P = 0.09) were predictors of poorer QOL. Physical functioning correlated positively with employment (P = 0.0001), and inversely with AIDS (P = 0.0002), hopelessness (P = 0.03), avoidant coping (P = 0.03), and age (P = 0.10). At 6 months follow up, QOL score had changed in 20% of the patients; older age (P = 0.01), and lesser satisfaction with social support (P = 0.15) were associated with a decline in QOL, while adherence with antiretroviral therapy (P = 0.006) was associated with an increase in QOL score. Seven of 138 patients died during follow up; these patients had significantly lower QOL at baseline than all other patients (P = 0.003). Interventions to alleviate hopelessness, maladaptive coping, and enhancement of satisfaction with social support may improve overall QOL in HIV-infected patients. Older patients with HIV were less satisfied with their social support, were more likely to utilize unhealthy coping styles, and experienced a greater decline in QOL over time.