Importance HIV-infected individuals with suppressed viremia on combined antiretroviral therapy (ART) have an increased risk of myocardial infarction (MI) versus uninfected control subjects. Effects of ART on arterial inflammation among treatment-naïve individuals with HIV are unknown. Objective To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naïve HIV-infected patients. Design, Setting, Participants 12 treatment-naïve HIV-infected subjects underwent 18fluorine-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) scanning for assessment of arterial inflammation, coronary CT angiography (CCTA) for assessment of subclinical atherosclerosis, and systemic immune/metabolic phenotyping prior to and 6 months after the initiation of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF). Systemic immune / metabolic parameters were also assessed in 12 prospectively recruited, non-HIV control subjects. The study began in July 2012 and was completed in May 2015. Intervention E/C/F/TDF in the HIV-infected cohort Results In addition to suppressing viral load (P<0.0001) and increasing CD4 count (P=0.0005), E/C/F/TDF markedly reduced the percentages of circulating activated CD4+ T cells (HLA-DR+CD38+CD4+) (P=0.008) and CD8+ T cells (HLA-DR+CD38+CD8+) (P=0.008), increased the percentage of circulating classical CD14+CD16− monocytes (P=0.04), and reduced levels of CXCL10 (P=0.03). With E/C/F/TDF, uptake of 18F-FDG in the axillary lymph nodes, as measured by target-to-background ratio (TBR), decreased from 3.7 (1.3, 7.0) at baseline to 1.4 (0.9, 1.9) [median (IQR) (P=0.01)] at study end. In contrast, no decrease was seen in aortic TBR in response to E/C/F/TDF (1.9±0.2 [2.0 (1.8, 2.1)] at baseline to 2.2±0.4 [2.1 (1.9, 2.6)] at study end, P=0.04 by two-way test; P=0.98 for test of decrease by one-way test). Changes in aortic TBR during E/C/F/TDF were significantly associated with changes in lipoprotein-associated phospholipase A2 (Lp-PLA2) (r=0.67, P=0.03). Coronary plaque increased among those HIV-infected participants with baseline plaque (n=3) and developed de novo in one participant during treatment with E/C/F/TDF. Conclusions and Relevance Newly initiated E/C/F/TDF in treatment-naïve HIV-infected subjects had discordant effects to restore immune homeostasis and dampen systemic immune activation without reducing arterial inflammation over the duration of treatment in this study. Complementary strategies to reduce arterial inflammation among ART-treated HIV-infected individuals may be needed. Clinical Trial Registration Number NCT01766726.

Objective(s) To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status. Design Cross-sectional evaluation. Methods Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known CVD were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and antimullerian hormone (AMH) levels. Participants underwent contrast enhanced coronary computed tomography angiography (CCTA) and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group. Results Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52% versus 6%, p=0.0007) and noncalcified plaque (48% versus 6%, p=0.002), as well as higher levels of log sCD163 (p=0.0004) and log MCP-1 (p=0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (p=0.04) and sCD163 (p=0.03). Conclusions HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population.

NCT02542371.

The relationship between violence in childhood and poorer educational outcomes is multi-faceted, potentially bi-directional, and manifests differently between genders. This research highlights the need for targeted research, policy and programming responses for prevention of violence.