Increase in Non-AIDS Related Conditions as Causes of Death among HIV-Infected Individuals in the HAART Era in Brazil

Background. In 1996, Brazil became the first developing country to provide free and universal access to HAART. Although a decrease in overall mortality has been documented, there are no published data on the impact of HAART on causes of death among HIV-infected individuals in Brazil. We assessed temporal trends of mortality due to cardiovascular diseases (CVD), diabetes mellitus (DM) and other conditions generally not associated with HIV-infection among persons with and without HIV infection in Brazil between 1999 and 2004. Methodology/Principal Findings. Odds ratios were used to compare causes of death in individuals who had HIV/AIDS listed on any field of the death certificate with those who did not. Logistic regression models were fitted with generalized estimating equations to account for spatial correlation; co-variables were added to the models to control for potential confounding. Of 5,856,056 deaths reported in Brazil between 1999 and 2004 67,249 (1.15%) had HIV/AIDS listed on the death certificate and non-HIV-related conditions were listed on 16.3% in 1999, Increasing to 24.1% by 2004 (p<0.001) The adjusted average yearly increases were 8% and 0.8% for CVD (p<0.001), and 12% and 2.8% for DM (p<0.001), for those who had and kiki not have HIV/AIDS listed on the death certificate respectively. Similar results were found for these conditions as underlying causes of death. Conclusions/Significance. In Brazil between 1999 and 2004 conditions usually considered not to be related to HIV-infection appeared to become more likely causes of death over time than reported causes of death among individuals who had HIV/AIDS listed on the death certificate than in those who did not. This observation has important programmatic implications for developing countries that are scaling-up access to antiretroviral therapy. © 2008 Pacheco et al

Antiretroviral Therapy, Renal Function among HIV-Infected Tanzanian, Adults, HIV/AIDS, .

Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting. We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4(+) T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs). In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR <90 mL/min/1.73 m(2)) decreased from 131/171 (76.6%) at the time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001). Moderate dysfunction (eGFR<60 mL/min/1.73 m(2)) decreased from 21.1% at antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not associated with renal dysfunction at follow-up. Mild and moderate renal dysfunction were common in this cohort of HIV-infected adults initiating antiretroviral therapy, and both significantly improved after a median follow-up time of 2 years. Our work supports the renal safety of antiretroviral therapy in African adults with mild-moderate renal dysfunction, suggesting that these regimens do not lead to renal damage in the majority of patients and that they may even improve renal function in patients with mild to moderate renal dysfunction

Development of Non-Natural Flavanones as Antimicrobial Agents

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non-natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 µg/mL in E. coli when combined with the inhibitor Phe-Arg-ß-naphthylamide, and MICs of 30 µg/mL in S. cerevesiae and 30 µg/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells

Widening of Socioeconomic Inequalities in U.S. Death Rates, 1993–2001

Background: Socioeconomic inequalities in death rates from all causes combined widened from 1960 until 1990 in the U.S., largely because cardiovascular death rates decreased more slowly in lower than in higher socioeconomic groups. However, no studies have examined trends in inequalities using recent US national data. Methodology/Principal Findings: We calculated annual age-standardized death rates from 1993–2001 for 25–64 year old non-Hispanic whites and blacks by level of education for all causes and for the seven most common causes of death using death certificate information from 43 states and Washington, D.C. Regression analysis was used to estimate annual percent change. The inequalities in all cause death rates between Americans with less than high school education and college graduates increased rapidly from 1993 to 2001 due to both significant decreases in mortality from all causes, heart disease, cancer, stroke, and other conditions in the most educated and lack of change or increases among the least educated. For white women, the all cause death rate increased significantly by 3.2 percent per year in the least educated and by 0.7 percent per year in high school graduates. The rate ratio (RR) comparing the least versus most educated increased from 2.9 (95 % CI, 2.8–3.1) in 1993 to 4.4 (4.1–4.6) in 2001 among white men, from 2.1 (1.8–2.5) to 3.4 (2.9–3–9) in black men, and from 2.6 (2.4–2.7) to 3.8 (3.6–4.0) in white women. Conclusion: Socioeconomic inequalities in mortality are increasing rapidly due to continued progress by educated whit