Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection

Context  Plasma human immunodeficiency virus (HIV) RNA level predicts HIV disease progression, but the extent to which it explains the variability in rate of CD4 cell depletion is poorly characterized. Objective  To estimate the proportion of variability in rate of CD4 cell loss predicted by presenting plasma HIV RNA levels in untreated HIV-infected persons. Design  Repeated-measures analyses of 2 multicenter cohorts, comprising observations beginning on May 12, 1984, and ending on August 26, 2004. Analyses were conducted between August 2004 and March 2006. Setting  Two cohorts of HIV-infected persons: patients followed up at 4 US teaching medical institutions or participating in either the Research in Access to Care for the Homeless Cohort (REACH) or the San Francisco Men's Health Study (SFMHS) cohorts and participants in the Multicenter AIDS Cohort Study (MACS) cohort. Participants  Antiretroviral treatment–naive, chronically HIV-infected persons (n = 1289 and n = 1512 for each of the 2 cohorts) untreated during the observation period (6 months) and with at least 1 HIV RNA level and 2 CD4 cell counts available. Approximately 35% were nonwhite, and 35% had risk factors other than male-to-male sexual contact. Main Outcome Measures  The extent to which presenting plasma HIV RNA level could explain the rate of model-derived yearly CD4 cell loss, as estimated by the coefficient of determination (R²). Results  In both cohorts, higher presenting HIV RNA levels were associated with greater subsequent CD4 cell decline. In the study cohort, median model–estimated CD4 cell decrease among participants with HIV RNA levels of 500 or less, 501 to 2000, 2001 to 10 000, 10 001 to 40 000, and more than 40 000 copies/mL were 20, 39, 48, 56, and 78 cells/µL, respectively. Despite this trend across broad categories of HIV RNA levels, only a small proportion of CD4 cell loss variability (4%-6%) could be explained by presenting plasma HIV RNA level. Analyses using multiple HIV RNA measurements or restricting to participants with high HIV RNA levels improved this correlation minimally (R², 0.09), and measurement error was estimated to attenuate these associations only marginally (deattenuated R² in the 2 cohorts, 0.05 and 0.08, respectively). Conclusions  Presenting HIV RNA level predicts the rate of CD4 cell decline only minimally in untreated persons. Other factors, as yet undefined, likely drive CD4 cell losses in HIV infection. These findings have implications for treatment decisions in HIV infection and for understanding the pathogenesis of progressive immune deficiency.      

Conservative treatment as an option in the management of pancreatic pseudocyst

BACKGROUND: Management of pancreatic pseudocysts is associated with considerable morbidity (15-25%). Traditionally, pancreatic pseudocysts have been drained because of the perceived risks of complications including infection, rupture or haemorrhage. We have adopted a more conservative approach with drainage only for uncontrolled pain or gastric outlet obstruction. This study reports our experience. PATIENTS AND METHODS: A consecutive series of 36 patients with pancreatic pseudocysts were treated over an 11-year period in one district general hospital serving a population of 310,000. This study group comprised of 19 men and 17 women with a median age of 55 years (range, 10-88 years). Twenty-two patients had a preceding attack of acute pancreatitis whilst 12 patients had clinical and radiological evidence of chronic pancreatitis. The aetiology comprised of gallstones (16), alcohol (5), trauma (2), tumour (2), hyperlipidaemia (1) and idiopathic (10). RESULTS: All patients were initially managed conservatively and intervention, either by radiological-assisted external drainage or cyst-enteric drainage (by surgery or endoscopy), was only performed for persisting symptoms or complications. Patients treated conservatively had 6 monthly follow-up abdominal ultrasound scans (USS) for 1 year. Fourteen of the 36 patients (39%) were successfully managed conservatively, whilst 22 patients required intervention either by percutaneous radiological drainage (12), by endoscopic cystogastrostomy (1) or by open surgical cyst-enteric anastomosis (9). Median size of the pancreatic pseudocysts in the 14 patients managed conservatively (7 cm) was nearly similar to that of the 22 patients requiring intervention (8 cm). The most common indications for invasive intervention in the 22 patients were persistent pain (16), gastric outlet obstruction (4), jaundice (1) and dyspepsia with weight loss (1). Although one patient required surgery for persistent pain, no other patients required urgent or scheduled surgery for complications of untreated pancreatic pseudocysts. Two of the 12 patients treated by percutaneous radiological drainage had recurrence of pancreatic pseudocysts requiring surgery. Two patients developed an intra-abdominal abscess following cyst-enteric drainage of pancreatic pseudocysts and one patient had a pulmonary embolism. On the mean follow-up of 37.3 months, one patient with alcoholic pancreatitis died 5 months after surgical cyst-enteric bypass. CONCLUSIONS: These results suggest that many patients with pancreatic pseudocysts can be managed conservatively if presenting symptoms can be controlled.