Background
Patients with HIV and low CD4 counts starting antiretroviral therapy (ART) are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death.
Methods
To investigate the clinical impact of IRIS in adults with HIV and CD4 counts below 100 cells/µL starting ART, we designed an international, prospective, observational study in United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We used Cox models to investigate associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48.
Results
We enrolled 506 participants, 39.3% of whom were women. Median age was 37 years (IQR 31-45) and CD4 T cell count was 29 cells/µL (IQR 11-56). Within 6 months of ART initiation, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at study start were at higher risk of IRIS (HR 1.2, p=0.004). IRIS was independently associated with increased risk of death even after adjustment for known risk factors (HR 3.2, P=0.031). In addition, being female (P=0.004), having lower BMI (P=0.003), higher WBC (P=0.005) and higher D-dimer levels (P=0.044) were also significantly associated with increased risk of death. Decision tree analysis identified hemoglobin less than 8.5 g/dL as highly predictive of IRIS and CRP>106 µg/ml and BMI < 15.6 kg/m2 as predictive of death .
Conclusions
For patients with HIV and severe immunosuppression who are initiating ART, baseline low BMI and hemoglobin, and high CRP and D-dimer may be clinically useful predictors of IRIS and death risk.
To determine the etiology of bloodstream infections (BSIs) in hospitalized patients >/=15 years old in Thailand, prospectively enrolled, consecutive febrile (>/=38 degrees C) patients were admitted to one hospital during February-April 1997. After a patient history was taken and a physical examination was performed, blood was obtained for comprehensive culture and human immunodeficiency virus (HIV) testing. Of 246 study patients, 119 (48%) had BSIs, and 182 (74%) were infected with HIV. The 2 most common pathogens were Cryptococcus neoformans and Mycobacterium tuberculosis (30 and 27 patients, respectively). HIV-positive patients were more likely than HIV-negative patients to have mycobacteremia (57/182 vs. 0/64, P<. 0001), fungemia (38/182 vs. 2/64, P<.001), or polymicrobial BSIs (19/182 vs. 0/64, P<.002). Clinical predictors of BSIs included HIV infection, chronic diarrhea, lymphadenopathy, or splenomegaly. Mortality was higher among patients with than those without BSIs (P<. 001). Cohort-based microbiologic studies are critically important to diagnose emerging pathogens and to develop algorithms for empirical treatment of BSIs in developing countries.
Coadministration of rifampicin with fluconazole caused significant changes in the pharmacokinetic parameters of fluconazole. Long-term monitoring for recurrence rates of cryptococcal meningitis is required to assess the clinical significance of this interaction.
Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin.
Survival from the time of AIDS diagnosis to death was determined retrospectively among Thai patients (> or = 13 years old) who attended a public tertiary care infectious disease hospital in a suburb of Bangkok, Thailand, from February 1987 through February 1993. An AIDS diagnosis was based on the 1987 Centers for Disease Control (CDC) definition, except Penicillium marneffei infection was included as an AIDS-defining condition. Of 329 AIDS patients, 152 (46.2%) had died. The median age at diagnosis was 31.5 years (range, 18-74) 306 patients (93.0%) were males. Reported risk categories were heterosexual contact (55.2%), injecting drug use (IDU, 22.6%), male homosexual or bisexual contact (9.5%), and unidentified risk or other (12.7%). Median survival time (Kaplan-Meier) for all patients was 7.0 months; 1-year survival probability was 39.2% (95% confidence interval [CI] = 31.5-46.9%). Cox's proportional hazards model showed three factors associated with survival: age, reported risk category, and presenting diagnosis. Patients aged 26 to 35 years survived longer (median survival time, 10.6 months; relative hazard [RH] = 0.61, 95% CI = 0.44-0.85, referent: others), as did patients in sexual risk categories (median survival time, 7.3 months; RH = 0.59, 95% CI = 0.40-0.78, referent: IDU and other categories). A single presenting diagnosis of extrapulmonary tuberculosis was also associated with longer survival (median survival time, 19.9 months, RH = 0.55, 95% CI = 0.35-0.86, referent: other diagnoses). AIDS patients in the early phase of the epidemic in Bangkok have much shorter survival times than patients in developed countries, in part perhaps because they are often diagnosed late in the course of HIV infection. Increased attention should be given to the early diagnosis and treatment of these patients.
The aim of this study was to investigate safety and impact of temporary external lumbar drainage for continuous release of cerebrospinal fluid among patients with HIV-associated cryptococcal meningitis and elevated intracranial pressure (ICP). We conducted a retrospective cohort study among patients with cryptococcal meningitis in whom temporary external lumbar drains were placed to reduce intractable elevated ICP between January 2002 and December 2005. Patients were followed for three months after the procedure. Among 601 HIV-infected patients with cryptococcal meningitis, 54 (8.9%) underwent lumbar drain placement. Of these patients, mean age was 33 years and 80% were males. The median duration of an indwelling lumbar drain was seven days. There were 61 placement procedures among 54 patients, totalling to 473 device-days of observation. Overall incidence of secondary bacterial infections was 6.3 per 1000 device-days, and three (4.9%) of 61 catheters became secondarily infected with nosocomially acquired bacteria. All three drains were removed and appropriate antibiotics were given. There was no difference in median duration of placement between infected and uninfected drains (six days vs. seven days, P=0.572). The overall mortality rate was 5.6% in this cohort of 54 patients. In conclusion, the incidence of nosocomial infection of external lumbar drains is low. In resource-limited settings, the use of temporary external lumbar drainage is a safe and effective management strategy for intractable elevated ICP in HIV-infected patients with cryptococcal meningitis.
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