Sabina A. Haberlen

Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study

Background Despite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV− men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography. Methods and Results Outcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin‐6 (IL‐6), intercellular adhesion molecule‐1, C‐reactive protein, and soluble‐tumor necrosis factor‐α receptor (sTNFαR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log‐interleukin‐6 and log intercellular adhesion molecule‐1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis ≥50% (all P<0.05). Similarly, sTNFαR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis ≥70% (P<0.05). Higher levels of interleukin‐6, sTNFαR I, and sTNFαR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01). Conclusions Higher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals.

Safer disclosure of HIV serostatus for women living with HIV who experience or fear violence: a systematic review

Globally 56% of all married women are using a modern method of contraception up from less than 10% in 1960. In sub-Saharan Africa however only 19% of married women are using a modern method of contraception. Since nearly all family planning services require assistance from a health worker access to health workers is a principal supply-side determinant of family planning service use. This technical brief presents findings from a study that explored if and how health workforce measures differ between eastern and western Africa in an effort to identify factors that may have helped some countries to achieve important gains in contraceptive prevalence while other countries have not. The findings raise questions about whether government commitment and certain policy choices vis-a-vis health workforce distribution and qualifications—even when absolute levels of health worker density are low—could make a difference in the provision of family planning services in resource-constrained countries.Supporting individuals as they disclose their HIV serostatus may lead to a variety of individual and public health benefits. However, many women living with HIV are hesitant to disclose their HIV status due to fear of negative outcomes such as violence, abandonment, relationship dissolution and stigma.

A Cross-sectional Study of the Association Between Chronic Hepatitis C Virus Infection and Subclinical Coronary Atherosclerosis Among Participants in the Multicenter AIDS Cohort Study

BACKGROUND Hepatitis C virus (HCV) infection may increase the risk of cardiovascular disease (CVD). We evaluated the association of chronic HCV infection and coronary atherosclerosis among participants in the Multicenter AIDS Cohort Study. METHODS We assessed 994 men with or without human immunodeficiency virus (HIV) infection (87 of whom had chronic HCV infection) for coronary plaque, using noncontrast coronary computed tomography (CT); 755 also underwent CT angiography. We then evaluated the associations of chronic HCV infection and HIV infection with measures of plaque prevalence, extent, and stenosis. RESULTS After adjustment for demographic characteristics, HIV serostatus, behaviors, and CVD risk factors, chronic HCV infection was significantly associated with a higher prevalence of coronary artery calcium (prevalence ratio, 1.29; 95% confidence interval [CI], 1.02-1.63), any plaque (prevalence ratio, 1.26; 95% CI, 1.09-1.45), and noncalcified plaque (prevalence ratio, 1.42; 95% CI, 1.16-1.75). Chronic HCV infection and HIV infection were independently associated with the prevalence of any plaque and of noncalcified plaque, but there was no evidence of a synergistic effect due to HIV/HCV coinfection. The prevalences of coronary artery calcium, any plaque, noncalcified plaque, a mixture of noncalcified and calcified plaque, and calcified plaque were significantly higher among men with an HCV RNA load of ≥2 × 10(6) IU/mL, compared with findings among men without chronic HCV infection. CONCLUSIONS Chronic HCV infection is associated with subclinical CVD, suggesting that vigilant assessments of cardiovascular risk are warranted for HCV-infected individuals. Future research should determine whether HCV infection duration or HCV treatment influence coronary plaque development.

Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men

Background Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection. Methods We examined 778 women (74% HIV+) in the Womens Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years. Results Marker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque. Conclusions sCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.

Integration of Family Planning Services into HIV Care and Treatment Services: A Systematic Review

Evidence on the feasibility, effectiveness, and cost‐effectiveness of integrating family planning (FP) and HIV services has grown significantly since the 2004 Glion Call to Action. This systematic review adds to the knowledge base by characterizing the range of models used to integrate FP into HIV care and treatment, and synthesizing the evidence on integration outcomes among women living with HIV. Fourteen studies met our inclusion criteria, eight of which were published after the last systematic review on the topic in 2013. Overall, integration was associated with higher modern method contraceptive prevalence and knowledge, although there was insufficient evidence to evaluate its effects on unintended pregnancy or achieving safe and healthy pregnancy. Evidence for change in unmet need for FP was limited, although two of the three evaluations that measured unmet need suggested possible improvements associated with integrated services. However, improving access to FP services through integration was not always sufficient to increase the use of more effective (noncondom) modern methods among women who wanted to prevent pregnancy. Integration efforts, particularly in contexts where contraceptive use is low, must address community‐wide and HIV‐specific barriers to using effective FP methods alongside improving access to information, commodities, and services within routine HIV care.

Intestinal microbiota-produced trimethylamine-N-oxide and its association with coronary stenosis and HIV serostatus

Abstract:Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men.

Cardiovascular disease risk scores' relationship to subclinical cardiovascular disease among HIV-infected and HIV-uninfected men

Objective:To study cardiovascular disease risk score utility, we compared the association between Framingham Risk Score (FRS)/pooled cohort equation (PCE) categories and coronary artery plaque presence by HIV serostatus and evaluated whether D : A : D risk category more accurately identifies plaque in HIV-infected men. Design:Cross-sectional analysis within a substudy of the Multicenter AIDS Cohort Study. Methods:Cardiac computed tomography was performed to assess coronary plaque. We evaluated the association of plaque with increasing cardiovascular disease risk score category, stratified by HIV serostatus, using logistic regression. Receiver operating characteristic curves compared the discrimination of the scores for plaque by HIV serostatus. The sensitivity and specificity of the risk scores were compared in HIV-infected men. Results:The risk score category – plaque associations were stronger among HIV-uninfected men than HIV-infected men, except for noncalcified plaque. For example, the odds of coronary artery calcium more than 0 were 7.03 (95% confidence interval 4.21, 11.76) times greater among men in the PCE high-risk versus low-risk category among HIV-uninfected men, compared with just 3.13 (95% confidence interval 2.13, 4.61) times greater among men in the high-risk versus low-risk category among HIV-infected men. Among HIV-infected men, high-risk category by PCE identified the greatest percentage of men with plaque/stenosis, but with lower specificity than D : A : D and FRS. The prevalence of coronary artery calcium more than 0 among men in the PCE low-risk category was 26.5% (HIV-uninfected men) and 36.0% (HIV-infected men). Conclusions:FRS and PCE categories associate with plaque burden better in HIV-uninfected men. No risk score delivered both high sensitivity and specificity among HIV-infected men.

Antiretroviral Therapy Availability and HIV Disclosure to Spouse in Rakai, Uganda: A Longitudinal Population-Based Study.

Background: A decade after the rollout of antiretroviral therapy (ART) in sub-Saharan Africa, the effects of this structural change on social aspects of HIV, such as rates of HIV disclosure to partners, remain largely unmeasured. We evaluated whether the introduction of ART was associated with disclosure of HIV diagnosis to spouses in Rakai, Uganda, using longitudinal, population-based data. Methods: We identified individuals in marital/cohabitating unions who were newly diagnosed with HIV in Rakai Community Cohort Study surveys between 2000 and 2008, where ART was introduced in mid-2004. Using discrete-time survival analysis, we assessed the hazard of self-reported HIV disclosure to spouse after diagnosis pre-ART and post-ART rollout, adjusting for individual and union characteristics. Disclosure in the ART period was further stratified by ART initiation. Results: The analysis included 557 married adults, 264 of whom were diagnosed with HIV before ART was available (2000–2004), and 293 diagnosed after ART was introduced (2005–2008). The cumulative incidence of self-reported disclosure was 75.2% in the post-ART period, compared with 58.3% before ART availability [P < 0.001, adjusted hazard ratio: 1.46 (95% confidence interval: 1.16 to 1.83)]. In the post-ART period, observed disclosure rates were 39% (72 of 184) among those not in HIV care, 65% (82 of 126) among those in pre-ART care, and 85% (64 of 75) among persons on ART (P < 0.001). Conclusions: Treatment availability and use, especially ART initiation, was associated with increased self-disclosure of HIV diagnosis to partners. ART access may facilitate the prevention of transmission to uninfected partners and linkage to treatment for infected couples.

HIV infection is associated with increased fatty infiltration of the thigh muscle with aging independent of fat distribution

Background Lower muscle density on computed tomography (CT) provides a measure of fatty infiltration of muscle, an aspect of muscle quality that has been associated with metabolic abnormalities, weakness, decreased mobility, and increased fracture risk in older adults. We assessed the cross-sectional relationship between HIV serostatus, age, thigh muscle attenuation, and thigh muscle cross-sectional area (CSA). Methods Mean CT-quantified Hounsfield units (HU) of the thigh muscle bundle and CSA were evaluated in 368 HIV-infected and 145 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) Cardiovascular Substudy using multivariable linear regression. Models all were adjusted for HIV serostatus, age, race, and body mass index (BMI); each model was further adjusted for covariates that differed by HIV serostatus, including insulin resistance, hepatitis C, malignancy, smoking, alcohol use, and self-reported limitation in physical activity. Results HIV-infected men had greater thigh muscle CSA (p<0.001) but lower muscle density (p<0.001) compared to HIV-uninfected men. Muscle density remained lower in HIV-infected men (p = 0.001) when abdominal visceral adiposity, and thigh subcutaneous adipose tissue area were substituted for BMI in a multivariable model. Muscle density decreased by 0.16 HU per year (p<0.001) of increasing age among the HIV-infected men, but not in the HIV-uninfected men (HIV x age interaction -0.20 HU; p = 0.002). Conclusion HIV-infected men had lower thigh muscle density compared to HIV-uninfected men, and a more pronounced decline with increasing age, indicative of greater fatty infiltration. These findings suggest that lower muscle quality among HIV-infected persons may be a risk factor for impairments in physical function with aging.

Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis

Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV-) from the Womens Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P < .001), higher KYNA/TRP (P = .01), and similar kynurenic acid levels (P = .51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P < .001), while each SD increment in kynurenic acid (P = .02) and KYNA/TRP (P < .001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.