Chylomicron particle size and number, factor VII activation and dietary monounsaturated fatty acids.

This study evaluated the effects of substituting dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) on postprandial chylomicron (triacylglycerol (TAG), apolipoprotein B-48 (apo B-48) and retinyl ester (RE)), chylomicron particle size and factor VII (FVII) response when subjects were given a standard meal. In a controlled sequential design, 51 healthy young subjects followed an SFA-rich diet (Reference diet) for 8 weeks after which half of the subjects followed a moderate MUFA diet (n=25) and half followed a high MUFA diet (n=26) for 16 weeks. Fasting lipoprotein and lipid measurements were evaluated at baseline and at 8-week intervals during the Reference and MUFA diets. In 25 of the subjects (n=12 moderate MUFA, n=13 high MUFA), postprandial responses to a standard test meal containing RE and 13C-tripalmitin were investigated at the end of the Reference and the MUFA diet periods. Although there were no differences in the postprandial lipid markers (TAG, RE, 13C-TAG) on the two diets, the postprandial apo B-48 response (incremental area under the curve (IAUC)) was reduced by 21% on the moderate MUFA diet (NS) and by 54% on the high MUFA diet (P<0.01). The postprandial peak concentrations of apo B-48 were reduced by 33% on the moderate MUFA diet (P<0.01) and 48% on the high MUFA diet (P<0.001). Fasting values for factor VII activity (FVIIc), activated factor VII (FVIIa) or factor VII antigen (FVIIag) did not differ significantly when subjects were transferred from Reference to MUFA diets. However, the postprandial increases in coagulation FVII activity (FVIIc) were 18% lower and of activated FVII (FVIIa) were 17% lower on the moderate MUFA diet (NS). Postprandial increases in FVIIc and FVIIa were 50% (P<0.05) and 29% (P<0.07) lower on the high MUFA diet and the area under the postprandial FVIIc response curve (AUC) was also lower on the high MUFA diet (P<0.05). Significantly higher ratios of RE:apo B-48 (P<0.001) and 13C-palmitic acid:apo B-48 (P<0.01) during both MUFA diets suggest that the CMs formed carry larger amounts of dietary lipids per particle, reflecting an adaptation to form larger lipid droplets in the enterocyte when increased amounts of dietary MUFAs are fed. Smaller numbers of larger chylomicrons may explain attenuated activation of factor VII during the postprandial state when the background diet is rich in MUFA.

Out of the closet and into the trenches: gay male Baby Boomers, aging, and HIV/AIDS.

Regardless of HIV status, all gay male Baby Boomers are aging in a context strongly shaped by HIV/AIDS. For this subcohort within the Baby Boom generation, the disproportionately high volume of AIDS deaths among gay men aged 25-44 years at the epidemic's peak (1987-1996) created a cohort effect, decimating their social networks and shaping their personal and social lives during the epidemic, throughout their life course, and into later years. But despite these lasting effects on an entire cohort of gay men, relevant scholarship narrowly focuses on older HIV-positive gay men using clinical, psychological, and social network approaches. It thus makes inadequate use of the life course perspective, which, by attention to timing, agency, and interdependence, can uncover the myriad interlocking and longitudinal aspects of the epidemic that affect this group. This article argues for the application of this latter approach to research into the lasting impacts of HIV/AIDS on this cohort of gay men. We examine HIV/AIDS mortality within this cohort at the epidemic's height, these deaths' concentration in urban gay communities, and the growing and increasingly diverse population of HIV-positive gay men born in the Baby Boom Years. Our conclusion suggests that a fuller examination of the role of HIV/AIDS in the lives of gay male Baby Boomers, using a life course perspective, is critical to appreciating this generation's heterogeneity and to expanding knowledge of how later life is shaped by the intersection between historical events, personal biography, and social and community ties.

Late HIV diagnosis in Europe: a call for increased testing and awareness among general practitioners.

Major advancements in the treatment of HIV infection mean near normal life expectancy of persons diagnosed at an early stage of infection. Nevertheless, a significant proportion of HIV infected persons remain undiagnosed and are diagnosed at a late stage of infection, putting them at higher risk for preventable HIV-related morbidity and mortality and risking onward transmission to others. In Europe, half of people diagnosed with HIV in 2010 were diagnosed late with a CD4<350 cells/ul, at a point after which treatment should have begun. The causes of late diagnosis are manifold, and comprise barriers to testing at the patient, healthcare provider, and institutional level. Strategies to address barriers to HIV testing are essential to ensure prompt diagnosis. Routine universal HIV testing in general practice consisting of informed consent and a pre-test discussion is feasible and acceptable and should be considered in high prevalence areas to normalize HIV testing, reduce stigma, and reduce the number of infected individuals who are diagnosed late.

Auditing national HIV guidelines and policies: The United Kingdom CD4 Surveillance Scheme.

The United Kingdom's CD4 surveillance scheme monitors CD4 cell counts among HIV patients and is a national resource for HIV surveillance. It has driven public health policy and allowed auditing of national HIV testing, treatment and care guidelines. WE DEMONSTRATE ITS UTILITY THROUGH FOUR EXAMPLE OUTPUTS: median CD4 count at HIV diagnosis; late HIV diagnosis and short-term mortality; the timing of first CD4 count to indicate entry into HIV care; and the proportion of patients with CD4 counts <350 cells/mm3 receiving anti-retroviral therapy (ARV). In 2009, 95% (61,502/64,420) of adults living with diagnosed HIV infection had CD4 counts available. The median CD4 count at diagnosis increased from 276 to 335 cells/mm3 between 2000 and 2009, indicating modest improvements in HIV testing. In 2009, 52% of patients were diagnosed at a late stage of HIV infection (CD4 <350 cells/mm(3)); these individuals had a ten-fold risk of dying within a year of their diagnosis compared to those diagnosed promptly. In 2008, the national target of performing a CD4 count within 14 days of diagnosis was met for 61% of patients. National treatment guidelines have largely been met with 83% patients with CD4 <350 cells/mm(3) receiving ARV. The monitoring of CD4 counts is critical to HIV surveillance in the United Kingdom enabling the close monitoring of efforts to reduce morbidity and mortality associated with late diagnosis and underpins the auditing of policies and guidelines. These routine surveillance outputs can be generated at national and local levels to drive and monitor public health policy and prevention efforts.

Invasive pneumococcal disease among HIV-positive individuals, 2000-2009.

OBJECTIVES: To examine invasive pneumococcal disease (IPD) incidence, the impact of the 7-valent pneumococcal conjugate vaccines (PCV7s) programme on the distribution of Streptococcus pneumoniae serotypes and risk factors for IPD among HIV-positive adults. METHODS: We analysed adults (aged ≥15 years) reported to the HIV and IPD national datasets in England and Wales (2000-2009). Through data-linkage, changes in IPD incidence and serotype distribution were examined. Risk factors for IPD among HIV-positive adults were assessed using a case-control study. RESULTS: Among 63,109 HIV-positive adults, 951 were co-infected with IPD. The average annual incidence of IPD was 245 episodes per 100,000 HIV-positive adults and 246 of 100,000 among those aged 15-44 years. Incidence was higher among those not on antiretroviral therapy (ART) (281 of 100,000) and those with severe immunosuppression (563 of 100,000). Among 9283 adults aged 15-44 at IPD diagnosis, 2.4% were living with undiagnosed HIV. The proportion of IPD episodes in HIV-positive adults with serotypes covered by PCV7 was 23% in 2009, a 54% proportional reduction compared with pre-PCV7 (2000-2006); the reduction in adults of unknown HIV status was 70%. The proportion of IPD episodes among HIV-positive adults caused by serotypes covered by PCV13 was 61%. Significant risk factors for IPD in multivariate analysis included older aged (≥65 years), a lower nadir CD4 cell count and no previous ART. CONCLUSION: An HIV test should be offered and recommended to adults aged 15-44 years without other obvious IPD risk factors. Our study provides an evidence base to policy makers regarding the use of the new PCV13 in HIV-positive adults.

HIV transmission and high rates of late diagnoses among adults aged 50 years and over.

OBJECTIVES: Describe the epidemiology and impact of late diagnosis among older adults living with HIV and estimate age at infection. METHODS: Comparative national analyses between individuals diagnosed when aged 50 years and over with individuals diagnosed prior to 50 years. Age at infection was estimated using CD4 cell count at diagnosis. RESULTS: A total of 8255 older adults accessed HIV care in England, Wales and Northern Ireland in 2007, a 3.5-fold increase compared to 2000; with one in 10 individuals newly diagnosed in 2007. When compared with younger adults at diagnosis, older adults were significantly more likely to be men (74 vs. 58%; P < 0.001), infected through sex between men (40 vs. 34%; P < 0.001) and of white ethnicity (60 vs. 38%; P < 0.001). Older heterosexual adults were more likely to be infected within the UK (16 vs. 12%; P < 0.001), with evidence of travel abroad among white heterosexual men. Almost half (48%) of older adults were late presenters vs. a third (33%) of younger adults. Older late presenters were 14 times more likely to die within a year of diagnosis compared with older adults who were not diagnosed late (14 vs. 1%; P < 0.001) and had 2.4 times the risk of dying than younger late presenters. We estimate that nearly half (48%) of older adults diagnosed between 2000 and 2007 acquired their infection at age 50 and over. CONCLUSION: Our study provides evidence of HIV transmission, high rates of late presentation and an increased risk of short-term mortality among older adults. These findings highlight the need for increased targeted prevention efforts and strategies to increase HIV testing among older adults at risk of HIV.

Long-term monounsaturated fatty acid diets reduce platelet aggregation in healthy young subjects.

The aim of the present study was to compare the response of a range of atherogenic and thrombogenic risk markers to two dietary levels of saturated fatty acid (SFA) substitution with monounsaturated fatty acids (MUFA) in students living in a university hall of residence. Although the benefits of such diets have been reported for plasma lipoproteins in high-risk groups, more needs to be known about effects of more modest SFA-MUFA substitutions over the long term and in young healthy adults. In a parallel design over 16 weeks, fifty-one healthy young subjects were randomised to one of two diets: (1) a moderate-MUFA diet in which 16 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 25); (2) a high-MUFA diet in which 33 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 26). All subjects followed an 8-week run-in diet (reference diet), with a fatty acid composition close to the UK average values. There were no differences in plasma lipid responses between the two diets over 16 weeks of the study with similar reductions in total cholesterol (P<0.001) and LDL-cholesterol (P<0.01) in both groups; a small but significant reduction in HDL-cholesterol was also observed in both groups (P<0.01). Platelet responses to ADP (P<0.01) and arachidonic acid (P<0.05) differed with time on the two diets; at 16 weeks, platelet aggregatory response to ADP was significantly lower on the high-MUFA than the moderate-MUFA (P<0.01) diet; ADP responses were also significantly lower within this group at 8 (P<0.05) and 16 (P<0.01) weeks compared with baseline. There were no differences in fasting factor VII activity (factors VIIc and VIIag), fibrinogen concentration or tissue-type plasminogen activator activity between the diets. There were no differences in postprandial factor VIIc responses to a standard meal (area under the curve) between the diets after 16 weeks, but postprandial factor VIIc response was lower than on the high-MUFA diet compared with baseline (P<0.01). In conclusion, a high-MUFA diet sustains potentially beneficial effects on platelet aggregation and postprandial activation of factor VII. Moderate or high substitution of MUFA for SFA achieves similar reductions in fasting blood lipids in young healthy subjects.