Isolated Nocturnal Hypertension in People Living With Human Immunodeficiency Virus: A Cross-Sectional Study.

BACKGROUND: Nocturnal hypertension (NH) is a potent cardiovascular risk factor described frequently in people with HIV (PWH). Isolated NH (INH) is less well reported in PWH because of the need for ambulatory blood pressure monitoring (ABPM) in office normotensive patients. We aim to document the prevalence of NH and INH and the clinical factors associated with these phenotypes. METHODS: Cross-sectional study from an HIV program in Argentina. Office and ABPM measurements, as well as clinical and laboratory exploration, were performed. We defined INH as NH with daytime normotension in patients with office normotension. RESULTS: We obtained ABPM in 66 PWH, 60% male, aged 44.7 (IQR 27-69) years; 87% receiving antiretroviral therapy, and 86.2% virologically suppressed. ABPM-based hypertension prevalence was 54.7% (95% CI: 42.5-66.3). The prevalence of NH was 48.5% (32/66), while the INH prevalence was 19.7% (95% CI: 11.7-30.9). No differences were found regarding sex, HIV viral load, CD4+ T lymphocytes count, or years of infection between normotensive and INH patients. Multiple linear regression model adjusted for sex and age determined that body mass index (ß = 0.93, P < 0.01), plasma uric acid (ß = 0.25, P = 0.04), plasma potassium (ß = -10.1, P = 0.01), and high-sensitivity C-reactive protein (hs-CRP) (ß = 0.78, P = 0.02) independently predicted nocturnal systolic blood pressure (BP) in PWH. In a multiple logistic regression model adjusted for age and sex, the presence of sedentariness, plasma potassium <4 mEq/L, BMI, and hs-CRP levels were predictors of INH. CONCLUSION: INH is highly prevalent in PWH. Metabolic and inflammatory markers predict nocturnal SBP in PWH.

Psychosocial Syndemic Classes and Longitudinal Transition Patterns Among Sexual Minority men Living with or Without HIV in the Multicenter AIDS Cohort Study (MACS).

Mental health and substance use epidemics interact to create psychosocial syndemics, accelerating poor health outcomes. Using latent class and latent transition analyses, we identified psychosocial syndemic phenotypes and their longitudinal transition pathways among sexual minority men (SMM) in the Multicenter AIDS Cohort Study (MACS, n = 3,384, mean age 44, 29% non-Hispanic Black, 51% with HIV). Self-reported depressive symptoms and substance use indices (i.e., smoking, hazardous drinking, marijuana, stimulant, and popper use) at the index visit, 3-year and 6-year follow-up were used to model psychosocial syndemics. Four latent classes were identified: "poly-behavioral" (19.4%), "smoking and depression" (21.7%), "illicit drug use" (13.8%), and "no conditions" (45.1%). Across all classes, over 80% of SMM remained in that same class over the follow-ups. SMM who experienced certain psychosocial clusters (e.g., illicit drug use) were less likely to transition to a less complex class. These people could benefit from targeted public health intervention and greater access to treatment resources.

Syndemic trajectories of heavy drinking, smoking, and depressive symptoms are associated with mortality in women living with HIV in the United States from 1994 to 2017.

BACKGROUND: Heavy drinking, smoking, and depression are common among people with HIV. Little is known about the co-occurring, synergistic effect of having two or more of these conditions long-term -a sustained syndemic - on mortality among women with HIV (WWH). METHODS: Data from 3282 WWH of the Women's Interagency HIV Study from 1994 to 2017 were utilized. National Death Index review identified cause of death (n=616). Sustained syndemic phenotypes were based on membership in high-risk groups defined by group-based trajectory models of repeated self-reported alcohol use, smoking, and depressive symptoms and their co-occurrence. Cox proportional hazard models estimated associations of sustained syndemic phenotypes with all-cause, non-AIDS, and non-overdose mortality, adjusting for age, race/ethnicity, education, enrollment wave, illicit drug use, and time-varying HIV viral load and CD4+ T-cell count. RESULTS: WWH were 58% Black and 26% Hispanic, with a mean baseline age of 36.7 years. Syndemic phenotypes included zero (45%, n=1463), heavy drinking only (1%, n=35), smoking only (28%, n=928), depressive symptoms only (9%, n=282), and 2+ trajectories (17%, n=574). Compared to zero trajectories, having 2+ trajectories was associated with 3.93 times greater all-cause mortality risk (95% CI 3.07, 5.04) after controlling for confounders and each high-risk trajectory alone. These findings persisted in sensitivity analyses, removing AIDS- and overdose-related mortalities. CONCLUSIONS: Clustering of 2+ conditions of heavy drinking, smoking, and depression affected nearly one in five WWH and was associated with higher mortality than zero or one condition. Our findings underscore the need for coordinated screening and parsimonious treatment strategies for these co-occurring conditions.

Bone, Brain, Heart study protocol: A resilient nested, tripartite prospective cohort study of the role of estrogen depletion on HIV pathology.

PURPOSE: We describe the rationale for and design of an innovative, nested, tripartite prospective observational cohort study examining whether relative estrogen insufficiency-induced inflammation amplifies HIV-induced inflammation to cause end organ damage and worsen age-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (Brain), skeletal (Bone), and cardiovascular (Heart/vessels) organ systems (BBH Study). METHODS: The BBH parent study is the Multicenter AIDS Cohort/Women's Interagency HIV Study Combined Cohort Study (MWCCS) with participants drawn from the Atlanta MWCCS site. BBH will enroll a single cohort of n = 120 women living with HIV and n = 60 HIV-negative women, equally distributed by menopausal status. The innovative multipart nested study design of BBH, which draws on data collected by the parent study, efficiently leverages resources for maximum research impact and requires extensive oversight and management in addition to careful implementation. The presence of strong infrastructure minimized BBH study disruptions due to changes in the parent study and the COVID-19 pandemic. CONCLUSION: BBH is poised to provide insight into sex and HIV associations with the neuro-hypothalamic-pituitary-adrenal axis, skeletal, and cardiovascular systems despite several major, unexpected challenges.

Association between BMI and periodontitis in women living with or at risk for HIV.

AIMS: Currently, there is no data available assessing the association between body mass index (BMI) and periodontitis among women living with HIV (WLWH). This study aims to investigate this association among WLWH and women at risk for HIV (WRH) in the United States. METHODS AND RESULTS: Data from 351 WLWH and 52 WRH participants from the Women's Interagency HIV Study having pocket depths and clinical periodontal attachment loss assessments in 2003-2004 were included. Multinomial logistic regression analyses in the full sample assessed the relationship between BMI (underweight/normal, overweight, or obese) and periodontitis by severity (mild, moderate, severe), adjusting for study sites, age, education, annual household income, smoking, alcohol consumption, and diabetes. Overall, 75.2% women (76.0% WLWH; 69.0% WRH) had periodontitis. Moreover, 75.0% obese and 75.3% overweight women were affected by periodontitis. In the full sample, adjusted odds ratio (aOR) of having mild, moderate, and severe periodontitis in obese women were: 1.14 (95% confidence interval [CI]: 0.51-2.52), 1.02 (95% CI: 0.46-2.29), and 0.24 (95% CI: 0.06-1.07), respectively, and in overweight women: 0.70 (95% CI: 0.31-1.58), 0.85 (95% CI: 0.38-1.90), and 0.31 (95% CI: 0.08-1.15), respectively. CONCLUSIONS: Even with high prevalence of periodontitis among women with or without HIV infection in this cohort, this study does not provide evidence of an association between BMI and periodontitis.

Weight Gain Associated With Integrase Stand Transfer Inhibitor Use in Women.

BACKGROUND: Integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for human immunodeficiency virus (HIV) management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) have been underrepresented in research. We evaluated the effect of switching or adding INSTIs among WLHIV. METHODS: Women enrolled in the Women's Interagency HIV Study (WIHS) from 2006-2017 who switched to or added an INSTI to ART (SWAD group) were compared to women on non-INSTI ART (STAY group). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences were measured 6-12 months before and 6-18 months after the INSTI switch/add in SWAD participants, with comparable measurement time points in STAY participants. Linear regression models compared changes over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. RESULTS: We followed 1118 women (234 SWAD and 884 STAY) for a mean of 2.0 years (+/- 0.1 standard deviation [SD]; mean age 48.8 years, SD +/- 8.8); 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m2 in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all P values < .05). No differences in magnitudes of these changes were observed by INSTI type. CONCLUSIONS: In WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages, compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation.

Pilot Study of Markers for High-grade Anal Dysplasia in a Southern Cohort From the Women's Interagency Human Immunodeficiency Virus Study.

BACKGROUND: Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)-infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women's Interagency HIV Study cohort. METHODS: All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. RESULTS: Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27-29.18], P = .02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66-25.35], P = .007), but not significantly higher in women with positive anal methylation. CONCLUSIONS: Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

Factors Associated with High-Grade Anal Intraepithelial Lesion in HIV-Positive Men in a Southern U.S. City.

The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a retrospective chart review of HIV-infected men at the Grady Ponce de Leon Center HIV Clinic (Atlanta, GA) referred for high-resolution anoscopy (HRA), a procedure where anal tissue is examined under magnification and abnormal areas are biopsied. Between December 2013 and September 2015, 147 men underwent HRA: 72% were black, and 94% were men who have sex with men. CD4 count closest to time of HRA was a median 325 cells/mm3 (interquartile range 203-473), and 69% had an undetectable HIV viral load. Ninety-four percent had abnormal anal cytology [80% atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (LSIL) and 20% atypical squamous cells, cannot exclude HSIL/HSIL], and 97% had abnormal histology (35% LSIL, 65% HSIL). Statistically significant variables associated with HSIL included number of biopsies [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.13-2.14] and having ≥1 high-grade anal cytology in the last 12 months (OR 3.76, 95% CI 1.38-10.23). No significant association was found between HSIL and CD4, HIV viral load, or recent sexually transmitted infection. In this population, the burden of anal HSIL was extremely high, regardless of most recent anal cytology result. In newly diagnosed HIV-infected men with no history of anal cancer screening, performing HRA as primary anal cancer screening instead of cytology appears to be a viable option.