Isoniazid preventive therapy and 4-year incidence of pulmonary tuberculosis among HIV-infected Thai patients.

SETTING: Human immunodeficiency virus (HIV) clinics at two Thai tertiary care medical centres. OBJECTIVES: To evaluate the efficacy of tuberculin skin test (TST) guided isoniazid preventive therapy (IPT) in combination with antiretroviral therapy (ART) in the prevention of tuberculosis (TB). DESIGN: A 4-year prospective comparative study of patients at two HIV clinics: one performed TST at enrolment and, if positive, prescribed IPT (IPT group), while the other did not perform TST (non-IPT group). RESULTS: There were 200 patients included in each group. Baseline characteristics and drop-out rates were similar in both groups. The incidence of pulmonary TB over 4 years was not significantly different between the IPT and non-IPT groups (0.80 cases vs. 1.76 per 100 person-years [py], P = 0.13). However, the incidence of pulmonary TB in the non-IPT group was significantly higher during the first 6 months (8.60 vs. 0 cases/100 py, P = 0.01) and among patients with initial CD4 < 200 cells/l (9.41 vs. 0 cases/100 py, P = 0.02). The survival analyses demonstrated a protective effect of IPT (x(2) = 3.66, P = 0.04) for early TB. CONCLUSIONS: Benefit of IPT plus ART was evident only in the first 6 months of care. These findings suggest that TST-guided IPT should be routinely provided for HIV-infected patients after initial entry into medical care.

Detection by microneutralization of antibodies against avian influenza virus in an endemic avian influenza region.

Detection by microneutralization of low-titre antibodies (anti-H5 micro-NT titre ≤ 1:80) against avian influenza virus (H5N1) is usually taken to be a false-positive result. In this prospective study of 242 intensive-care unit patients admitted for severe community-acquired pneumonia, the prevalence of low-titre anti-H5 micro-NT was 2.4%. Prior exposure to poultry was the sole independent risk factor for these low-titre antibodies (adjusted OR 42.41; 95% CI 22.45-64.51; p <0.001). We suggest that low anti-H5 micro-NT titres be interpreted in conjunction with plausible poultry, environmental and human exposure to H5N1.

Intrathecal colistin for drug-resistant Acinetobacter baumannii central nervous system infection: a case series and systematic review.

Treatment limitations exist for drug-resistant Acinetobacter baumannii central nervous system (CNS) infection. We conducted a retrospective study and systematic literature review to identify patients with drug-resistant A. baumannii CNS infection who received primary or adjunct intrathecal or intraventricular (IT/IVT) colistin. In a case series of seven Thai patients and 17 patients identified in the literature, clinical and microbiological cure rates with IT/IVT colistin therapy were 83% and 92%, respectively. Three patients (13%) developed chemical ventriculitis and one (4%) experienced treatment-associated seizures. Death was associated with delayed IT/IVT colistin therapy compared to survival (mean time from diagnosis to IT/IVT colistin, 7 vs. 2 days; p 0.01). The only independent predictor of mortality was the severity of illness (APACHE II score > 19, adjusted odds ratio 49.5; 95% CI 1.7-1428.6; p 0.02). This case series suggests that administration of primary or adjunctive IT/IVT colistin therapy was effective for drug-resistant A. baumannii CNS infection.

Assessment of risk for pulmonary tuberculosis after non-reactive tuberculin skin testing among patients with HIV infection in a resource-limited setting.

SUMMARY: A cross-sectional study of 350 patients with HIV-1 infection was conducted to identify risks for pulmonary Mycobacterium tuberculosis (TB) after non-reactive two-step tuberculin skin tests (TST). Among 219 patients (62.6%) with non-reactive TST, independent risks for active pulmonary TB were prior known TB exposure (adjusted odds ratio [aOR] = 16.00, 95% confidence interval [CI] = 2.00-26.36, P = 0.008), CD4 <100 cells/microL (aOR = 2.50, 95% CI = 1.30-6.50, P = 0.04) and less than secondary-school education (aOR = 2.60, 95% CI = 1.50-6.90, P = 0.02). Our findings suggest that further diagnostic work-up for pulmonary TB is warranted among patients with HIV infection, non-reactive TSTs and either prior known TB exposure, CD4 counts <100 cells/microL or limited formal education.

Secure antiretroviral therapy delivery in a resource-limited setting: streamlined to minimize drug resistance and expense.

BACKGROUND: We report the design and analysis of a streamlined approach to the delivery of antiretroviral therapy (ART) that minimized risk for emergence of ART drug resistance (ART-DR) in a resource-limited setting. METHODS: The algorithm of care for persons with HIV comprised generic, fixed-dose, twice-daily stavudine, lamivudine and nevirapine (GPO-VIR), scheduled and unannounced pill counts and measurement of viral load at months 6 and 18 after initiation of ART. We evaluated adherence as measured by pill counts, HIV suppression and programmatic costs. RESULTS: Over a 4-year period, 214 of 330 patients (64.8%) were enrolled; baseline median CD4 count was 84 cells/microL. At month 1, nine patients (4.2%) discontinued GPO-VIR because of skin rash. At month 6, 199 patients (93%) achieved viral load < or =400 HIV-1 RNA copies/mL, with current alcohol use the sole predictor of treatment failure [adjusted Relative Risk (aRR)=1.67; 95% confidence interval=1.05-2.48; P<0.001]. Most patients (97%) with HIV suppression at month 6 had viral loads < or =50 copies/mL at month 18; all had > or =75% visit compliance and 192 (98%) had > or =75% adherence measured by pill counts. The estimated annual costs were $111.92 per patient for the pill counts, home visits and viral load measurement. CONCLUSIONS: Secure ART delivery, while minimizing risk for non-adherence and ART-DR, is clinically and economically feasible in this resource-limited setting.

Antiretroviral drug resistance among antiretroviral-naïve persons with recent HIV infection in Thailand.

OBJECTIVES: To evaluate the prevalence and patterns of antiretroviral (ARV) drug resistance (ARV-DR) among ARV drug-naïve, recently infected persons with HIV in the 4-year interval (2003-2006) after the inception of the National Access to ARV Programme for People who have AIDS in Thailand. METHODS: Cross-sectional study of patients with recent HIV infection for HIV risks, ARV-DR risks and baseline ARV-DR. RESULTS: Seven of the 305 patients (2%) had baseline ARV-DR. Via contract tracing, all seven patients with transmitted ARV-DR identified sexual partners with prior ARV treatment failure and had documented low (<75%) ARV adherence. Annual ARV-DR increased from 0 to 5.2% (P=0.06) between 2003 and 2006. CONCLUSIONS: Report of sexual partners with potential HIV and ARV drug exposures can prompt baseline ARV-DR testing of at-risk individuals, while behavioural interventions for adherence and safer sex are refined to minimize the emergence of resistance to generic, fixed-dose combination stavudine, lamivudine and nevirapine (GPO-VIR) therapy.

Clostridium difficile: emergence of hypervirulence and fluoroquinolone resistance.

Clostridium difficile is a well-known cause of sporadic and healthcare-associated diarrhea. Multihospital outbreaks due to a single strain and outbreaks associated with antibiotic selective pressure, especially clindamycin, have been well documented. Severe cases and fatalities from C. difficile are uncommon. The recent global emergence of a hypervirulent strain containing binary toxin (Toxinotype III ribotype 027), with or without deletion in a regulatory gene (tcdC gene), together with high-level resistance to third generation fluoroquinolones, has been associated with increased morbidity and mortality. Although the defective regulatory gene locus is associated with increased toxin production in vitro, the in vivo significance of this mutation and of the binary toxin remains undefined. To date, treatment strategies have not evolved in response to the emergence of this hypervirulaent strain. We provide a critical, quantitative summary of the evolving clinical and molecular epidemiology of C. difficile along with implications relevant to future treatment strategies.

Non-neoformans cryptococcal infections: a systematic review.

Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age > or =45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.

Vancomycin-resistant enterococcal bloodstream infections on a hematopoietic stem cell transplant unit: are the sick getting sicker?

Patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients are at high risk for bacterial bloodstream infections (BSI) owing to resistant organisms. Data describing the outcomes of vancomycin-resistant enterococcal (VRE) BSI in this patient population are limited. We performed a retrospective cohort study of all cases of VRE BSI that occurred between February 1996 and December 2002 on the Leukemia/HSCT unit at Barnes-Jewish Hospital. There were 68 episodes of VRE BSI in 60 patients with acute (53%) or chronic (8%) leukemia, non-Hodgkin's lymphoma (22%) or other malignant hematologic disorders (17%). A total of 13, 32 and 32% were recipients of autologous, related and matched-unrelated transplants, respectively. Forty-two of allograft recipients had active acute graft-versus-host disease (GVHD) and 32% chronic GVHD. Only 57% were neutropenic, 52% had refractory/relapsed malignancy and 60% had end organ dysfunction with a median APACHE II score of 17. Median survival after VRE BSI was 19 days. Pneumonia, receipt of anti-fungal drugs and low APACHE II score at the time of the VRE BSI remained significant risk factors for death on multivariable analysis. Our analysis suggests that in patients with hematological malignancies or HSCT, VRE may not have the behavior of a virulent pathogen. VRE BSI may simply be a marker of these patients' already existing critical medical condition.

The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy.

The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple composite measure of self-reported antiretroviral therapy (ART) adherence, was compared to a standard three-day self-reported adherence measure among participants in a longitudinal, prospective cross-site evaluation of 12 adherence programs throughout the United States. The CASE Adherence Index, consisting of three unique adherence questions developed for the cross-site study, along with a three-day adherence self-report were administered by interviews every three months over a one-year period. Data from the three cross-site adherence questions (individually and in combination) were compared to three -day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence Index correlated strongly with the three-day self-reported adherence data (p < 0.001) and was more strongly associated with HIV outcomes, including a 1-log decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA < 400 copies/ml (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report when predicting CD4 count status. Participants with a CASE Index score >10 achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41 cell increase for those with scores < or =10 (p < 0.05). The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical settings.

Women with HIV infection: a model of university-based care, training and research.

The growth of human immunodeficiency virus type-1 (HIV) infection among women in the USA has been coincident with an international momentum to better address the specific health care needs of women. This paper provides an overview of a demonstration model for comprehensive HIV care of adolescent and adult women in an academic setting. The paper contains a descriptive summary of a university-based demonstration model of comprehensive care for women with HIV infection. During 1997-1998, there were 279 urban and rural Midwest adolescent and adult women with HIV infection in care at this model programme. Medical care encompassed subspecialty HIV care, obstetrical and gynaecological care, primary care of non-HIV comorbidities, mental health assessments and family planning in a safe, university-based environment. For 279 women during the two-year period, health services included the detection and treatment of sexually transmitted diseases (56%) and cervical dysplasia (35%), perinatal care (12%) and screening and referral for substance abuse treatment (30%). There was no mother-to-child HIV transmission among 33 pregnant women enrolled in the Center prior to delivery, and transmission by three of nine women enrolled after delivery. Only 167 (60%) women were compliant with biannual medical visits during 1997-1998. Integral to the health services delivery was the provision of ancillary support services intended to enhance optimal medical care for this cohort of women. This university-based model of care also incorporated HIV provider training and formative HIV research. Structured medical and public health experiential learning opportunities occurred for medical and social work students, medicine residents, infectious diseases fellows, nurses and other professional health care workers. Clinical investigations of adolescent and adult women have complemented care and training, with funded research in HIV medication adherence and health services research. In follow-up, 71% of these women remained active in care in 1999. Retention of vulnerable populations in care may be a big challenge over the next decade, despite the availability of potent antiretroviral therapies.

Acute flaccid paralysis syndrome associated with echovirus 19, managed with pleconaril and intravenous immunoglobulin.

We describe a 39-year-old woman who had undergone bilateral lung and renal transplantation and who was admitted to the hospital with acute onset of flaccid paralysis of the left leg due to echovirus 19 infection. The patient was treated with pleconaril and intravenous immunoglobulin, which correlated with clinical and laboratory evidence of improvement.

Evaluation of zinc bacitracin capsules versus placebo for enteric eradication of vancomycin-resistant Enterococcus faecium.

Patients who are colonized with enteric vancomycin-resistant Enterococcus faecium (VREF) are a major reservoir for transmission of and infection with this organism. In a randomized, controlled study to assess the effectiveness of high-dose bacitracin in the eradication of enteric VREF, 12 patients who were colonized with VREF were randomized to receive placebo (n=6) or orally administered zinc bacitracin (n=6) for 10 days. Posttreatment perirectal or stool cultures indicated that after 3 weeks, VREF had been eradicated from the stool of only 2 (33%) of 6 patients in each group. Of the 8 remaining patients who were still VREF-positive at 3 weeks after treatment, 5 (62%) had later evidence of spontaneous enteric eradication at 8 weeks. Further testing of VREF isolates revealed that a significant number (n=22, 76%) were resistant to bacitracin and that patients may have been colonized with multiple different VREF strains. Although bacitracin was not effective in the enteric eradication of VREF, the high rates of spontaneous eradication suggest that other host and environmental factors are more important in achieving long-term suppression or elimination of VREF colonization.

Women's HIV transmission risk perceptions and behaviors in the era of potent antiretroviral therapies.

The availability of potent antiretroviral medications has raised new concerns regarding continued HIV transmission risk behavior among seropositive persons. Relatively little is known about how women with HIV perceive secondary transmission risk in the context of HIV treatment advances. This study describes sexual risk perceptions and behaviors of 80 women enrolled in HIV outpatient care in 1999. Participants completed structured interviews assessing sexual risk perceptions, attitudes regarding severity of HIV disease, sources of HIV prevention information, and sexual practices during the previous 6 months. Medical histories including 6-month cumulative incidence of sexually transmitted diseases (STDs) were obtained from a clinic database. Thirty-five percent of the sample had engaged in unprotected intercourse or had been diagnosed with an STD in the past 6 months. Only 5% of women believed that medication-related reductions in viral load signify safer sex is unimportant, but 15% indicated they practice safer sex less often since the advent of new HIV treatments and 40% believed AIDS is now a less serious threat. These data suggest women's perceptions of diminished disease severity may be more influential than beliefs regarding diminished infectivity. Study results have implications for framing prevention messages for women and suggest that close integration of secondary prevention and clinical HIV services may be beneficial.

Acquisition of vancomycin-resistant enterococci during scheduled antimicrobial rotation in an intensive care unit.

Scheduled rotation of treatment of gram-negative antimicrobial agents has been associated with reduction of serious gram-negative infections. The impact of this practice on other nosocomial infections has not been assessed. The purpose of this study was to determine if scheduled antimicrobial rotation reduced rates of acquisition of enteric vancomycin-resistant enterococci (VRE) among 740 patients admitted to an intensive care unit (ICU). The preferred gram-negative agent was ceftazidime during rotation 1 and ciprofloxacin during rotation 2. Unadjusted VRE acquisition rates were 8.5 cases per 1000 ICU days and 11.7 cases per 1000 ICU days during rotations 1 and 2, respectively (P<.01). However, scheduled antimicrobial rotation of ceftazidime with ciprofloxacin had no effect on the risk of acquiring VRE in the ICU after adjustment for known risk factors. Independent predictors of acquisition of VRE were enteral feedings, higher colonization pressure, and increased duration of anaerobic therapy. Our findings can confirm no additional beneficial or adverse effect on VRE acquisition among ICU patients as a result of this practice.

Finding the underserved: directions for HIV care in the future.

The demographic, behavior, and background characteristics of 4,804 participants in 17 national demonstration projects for HIV medical and/or psychosocial support services were coded for an index of "service need" or possible under-representation in the traditional healthcare system. Fifteen items were coded including status as a person of color, lack of private insurance, unemployment/disability, problem drinking, crack cocaine use, heroin use, other illicit drug use, less than 12 years of education, criminal justice system involvement, children requiring care while the patient receives services, sex work, being the sex partner of an injection drug user, unstable housing, primary language not English, and age less than 21 or over 55 years. Most (87.7%) of the program participants had four or more of these factors present. Through CHAID modeling, those groups with the highest levels of service need and vulnerability were identified. These data suggest that these projects, designed to attract and serve individuals potentially underrepresented in the health services system, had in fact achieved that goal. Implications of the changing demographics of the HIV epidemic for the health service delivery system are discussed.

Sources influencing patients in their HIV medication decisions.

The authors surveyed 202 patients (54.5% male; 62.4% African American) enrolled at St. Louis HIV clinics to identify the importance of various sources of influence in their HIV medication decisions. Physicians were the most important source for 122 (60.4%) respondents, whereas prayer was most important for 24 respondents (11.9%). In multivariate tests controlling for CD4 counts, Caucasian men were more likely than Caucasian women and African Americans of both genders to select a physician as the most important source. African Americans were more likely than Caucasians to mention prayer as the most important source. Caucasians and those rating physicians as the most important source were more likely to be using antiretroviral medications. Respondents identified multiple important influences-hence the potential for conflicting messages about HIV medications. These findings have implications for health education practices and behavioral research in the medical setting.