Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA

<p>Abstract</p> <p>Background</p> <p>Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT.</p> <p>Methods</p> <p>In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression.</p> <p>Results</p> <p>In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections.</p> <p>More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery.</p> <p>Conclusion</p> <p>These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain.</p> <p>Trial registration</p> <p>NCT00000869</p

fMRI Evidence for a Dual Process Account of the Speed-Accuracy Tradeoff in Decision-Making

Background: The speed and accuracy of decision-making have a well-known trading relationship: hasty decisions are more prone to errors while careful, accurate judgments take more time. Despite the pervasiveness of this speed-accuracy tradeoff (SAT) in decision-making, its neural basis is still unknown. Methodology/Principal Findings: Using functional magnetic resonance imaging (fMRI) we show that emphasizing the speed of a perceptual decision at the expense of its accuracy lowers the amount of evidence-related activity in lateral prefrontal cortex. Moreover, this speed-accuracy difference in lateral prefrontal cortex activity correlates with the speedaccuracy difference in the decision criterion metric of signal detection theory. We also show that the same instructions increase baseline activity in a dorso-medial cortical area involved in the internal generation of actions. Conclusions/Significance: These findings suggest that the SAT is neurally implemented by modulating not only the amount of externally-derived sensory evidence used to make a decision, but also the internal urge to make a response. We propose that these processes combine to control the temporal dynamics of the speed-accuracy trade-off in decisionmaking

Delays in Protease Inhibitor Use in Clinical Practice

OBJECTIVE: To determine the clinical factors associated with delayed protease inhibitor initiation. DESIGN: Chart review and telephone survey. SETTING: General medicine practice at an academic medical center in Boston, Mass. PATIENTS: One hundred ninety patients living with HIV and a viral load of more than 10,000 copies/ml. MEASUREMENTS AND MAIN RESULTS: The main outcome measurement was time to first protease inhibitor prescription after first elevated HIV viral load (>10,000 copies/ml). In this cohort, 190 patients had an elevated viral load (median age 39; 87% male; 12% history of injection drug use; 63% AIDS; 53% with depression; 17% history of pneumocystis pneumonia; 54% CD4 <200). In Cox proportional hazards modeling, significant univariate correlates for delayed protease inhibitor initiation were higher CD4 cell count (hazard ratio [HR] 2.38 for CD4 200–500 compared with <200, 95% confidence interval [CI] 1.59, 3.57; and HR 8.33 for CD4> 500; 95% CI 2.63, 25.0), higher viral load (HR 0.43 for each 10-fold increase; 95% CI 0.31, 0.59), injection drug use (HR 2.08; 95% CI 1.05, 4.17), AIDS (HR 0.24; 95% CI 0.15, 0.36), and history of pneumocystis pneumonia (HR 0.32; 95% CI 0.21, 0.49). In multivariate models adjusted for secular trends in protease inhibitor use, factors significantly associated with delay of protease inhibitor initiation (p < .05) were higher CD4 cell count (for CD4 200–500, HR 2.63; 95% CI 1.61, 4.17; for CD4> 500, HR 11.11; 95% CI 3.57, 33.33), higher viral load (HR 0.66 for each 10-fold increase; 95% CI 0.45, 0.98), history of pneumocystis pneumonia (HR 0.57; 95% CI 0.37, 0.90), history of depression (HR 1.49; 95% CI 1.03, 2.13), and history of injection drug use (HR 2.70; 95% CI 1.35, 5.56). CONCLUSIONS: HIV-infected patients with higher CD4 cell counts or a history of depression or history of injection drug use have significant and lengthy delays of protease inhibitor therapy. Although some delays may be clinically appropriate, enhancement of provider and patient education might prove beneficial. Further research should examine reasons for delays in protease inhibitor initiation and their appropriateness