Prepandemic Metabolic Correlates of Coronavirus Disease 2019 (COVID-19) Severity and Long COVID Incidence in People Living With HIV.

Host metabolic dysregulation, especially in tryptophan metabolism, is intricately linked to coronavirus disease 2019 (COVID-19) severity and its postacute sequelae (long COVID). People living with human immunodeficiency virus (HIV; PLWH) experience similar metabolic dysregulation and face an increased risk of developing long COVID. However, whether preexisting HIV-associated metabolic dysregulations contribute in predisposing PLWH to severe COVID-19 outcomes remains underexplored. Analyzing prepandemic samples from PLWH with documented postinfection outcomes, we found specific metabolic alterations, including increased tryptophan catabolism, predicting an elevated risk of severe COVID-19 and the incidence of long COVID. These alterations warrant further investigation for their potential prognostic and mechanistic significance in determining COVID-19 complications.

Cardiovascular Implications of Immune Disorders in Women.

Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.

Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. METHODS: Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. RESULTS: Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. CONCLUSIONS: HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.

T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.

SUMMARY: In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. BACKGROUND: Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. METHODS: Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. RESULTS: At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. CONCLUSIONS: Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

Health insurance and AIDS Drug Assistance Program (ADAP) increases retention in care among women living with HIV in the United States.

Our objective was to examine the association between healthcare payer type and missed HIV care visits among 1,366 US women living with HIV (WLWH) enrolled in the prospective Women's Interagency HIV Study (WIHS). We collected secondary patient-level data (October 1, 2017-September 30, 2018) from WLWH at nine WIHS sites. We used bivariate and multivariable binary logistic regression to examine the relationship between healthcare payer type (cross-classification of patients' ADAP and health insurance enrollment) and missed visits-based retention in care, defined as no-show appointments for which patients did not reschedule. Our sample included all WLWH who self-reported having received HIV care at least once during the two consecutive biannual WIHS visits a year prior to October 1, 2017-September 30, 2018. In the bivariate model, compared to uninsured WLWH without ADAP, WLWH with private insurance + ADAP were more likely to be retained in care, as were WLWH with Medicaid only and private insurance only. In the adjusted model, WLWH with private insurance only were more likely to be retained in care compared to uninsured WLWH without ADAP. Private health insurance and ADAP are associated with increased odds of retention in care among WLWH.

Antiretroviral Therapy-Induced Bone Loss Is Durably Suppressed by a Single Dose of Zoledronic Acid in Treatment-Naive Persons with Human Immunodeficiency Virus Infection: A Phase IIB Trial.

BACKGROUND: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among persons with HIV (PWH). We previously showed long-acting antiresorptive zoledronic acid (ZOL) prevented ART-induced bone loss through 48 weeks of therapy and here investigate whether protection persisted. METHODS: We randomized 63 nonosteoporotic, treatment-naive adult PWH initiating ART to ZOL (5 mg) versus placebo in a double-blinded, placebo-controlled, phase IIb trial. Here we analyzed the long-term outcome data (144 weeks). Plasma bone turnover markers and bone mineral density (BMD) were quantified at weeks 0, 12, 24, 48, 96, and 144. Primary outcome was change in bone resorption marker C-terminal telopeptide of collagen (CTx). Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. RESULTS: At 96 weeks, mean CTx was 62% lower with ZOL relative to placebo (n = 46; CTx = 0.123 vs 0.324 ng/mL; P < .001); at 144 weeks a 25% difference between arms was not statistically significant. At 48 weeks, lumbar spine BMD with ZOL was 11% higher than placebo (n = 60; P < .001) and remained 9-11% higher at 96 (n = 46) and 144 (n = 41; P < .001) weeks. 144 weeks after ZOL infusion, BMD did not change at the lumbar spine (P = .22) but declined at the hip (P = .04) and femoral neck (P = .02). CONCLUSIONS: A single dose of ZOL administered at ART initiation blunts bone resorption and BMD loss at key fracture-prone anatomical sites in treatment-naive PWH for 3 years. A multicenter randomized phase III clinical trial validating these results in a larger population is needed. CLINICAL TRIALS REGISTRATION: NCT01228318.

Structures and Rotational Barriers of a Diiodobinorsnoutane: Energetic Preference for Gauche Conformation.

The diiodobinorsnoutane, bi(5-iodopentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-yl) (5), exists in a sterically hindered gauche conformation rather than an anti or an averaged (freely rotating) C2v structure. Density functional theory (DFT) predictions place the gauche conformation 11 kcal/mol more stable than the anti conformation with a barrier of 17 kcal/mol connecting the minima. These are consistent with variable-temperature NMR (17.1 ± 0.8 kcal/mol) estimates and X-ray analysis. Predictions of the torsional profiles of the yet-unsynthesized bromo-, chloro-, and fluoro- analogues show a progressive lowering of the barriers.

Substance use and menopausal symptoms among people with and without HIV in the US, 2008-2020.

OBJECTIVE: The aim of the study is to assess associations between substance use and menopausal symptoms among US people living with and without HIV in a longitudinal cohort. METHODS: We analyzed self-reported menopausal symptoms and substance use from biannual Women's Interagency HIV Study (WIHS) visits from 2008-2020. Substance use since the last visit or lifetime cumulative use included tobacco, alcohol, marijuana, crack/cocaine, and opioids. Logistic regression quantified associations between each substance use and menopausal symptom frequency (vasomotor, mood, and musculoskeletal), adjusting for other substance use, HIV status, demographics, comorbidities, and trauma. RESULTS: A total of 1,949 participants contributed early perimenopausal, late perimenopausal, or postmenopausal study visits. Across reproductive-aging stages, based on menstrual history, and among participants with and without HIV, participants reported frequent vasomotor (range 22-43%), mood (18-28%), and musculoskeletal (25-34%) symptoms. Many reported ever using tobacco (72%), heavy alcohol (75%), marijuana (73%), crack (50%), and opioids (31%). Current heavy alcohol use (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.10-1.37), cumulative marijuana use (OR: 1.15, 95% CI: 1.01-1.32), and cumulative tobacco use (OR: 1.06, 95% CI: 1.01-1.12) were associated with a higher frequency of vasomotor symptoms; current heavy alcohol use (OR: 1.20, 95% CI: 1.04-1.39) and current opioid use (OR: 1.13; 95% CI: 1.01-1.25) were associated with mood symptoms; and current opioid use (OR: 1.11, 95% CI: 1.00-1.23) was associated with musculoskeletal symptoms. All other associations were found to be null. CONCLUSIONS: Current and prior substance use may independently affect symptoms experienced during the menopausal transition and may indicate potential to benefit from additional intervention and referral to menopause specialty care.

Life course history of physical and sexual abuse is associated with cardiovascular disease risk among women living with and without HIV.

OBJECTIVE: Sexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH). METHODS: Using 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus. RESULTS: Among WLWH, childhood sexual abuse was associated with higher CVD risk ( ßFRS-H  = 1.25, SE = 1.08, P  = 0.005; ßACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( ßFRS-H  = 1.39, SE = 1.08, P  < 0.0001) and WLWOH ( ßFRS-H  = 1.58, SE = 1.14, P  = 0.0006). Childhood physical abuse was not associated with CVD risk for either group. Adulthood physical abuse was associated with CVD risk for WLWH ( ßFRS-H  = 1.44, SE = 1.07; P  < 0.0001, ßACC/AHA-PCE  = 1.18, SE = 1.06, P  = 0.002) and WLWOH ( ßFRS-H  = 1.68, SE = 1.12, P  < 0.0001; ßACC/AHA-PCE  = 1.24, SE = 1.11, P  = 0.03). Several pathway factors were significant, including depression, smoking, and hepatitis C infection. CONCLUSION: Life course abuse may increase CVD risk among WLWH and women at high risk of acquiring HIV. Some comorbidities help explain the associations. Assessing abuse experiences in clinical encounters may help contextualize cardiovascular risk among this vulnerable population and inform intervention.

The association between comorbidities and coronavirus disease 2019 hospitalization among people with HIV differs by age.

OBJECTIVES: To determine whether factors associated with coronavirus disease 2019 (COVID-19) hospitalization among people with HIV (PWH) differ by age stratum. DESIGN: Retrospective cohort study. METHODS: All adult PWH with a positive SARS-CoV-2 PCR in a public safety-net health system between 1 March 2020 and 28 February 2021 and a Veterans Affairs Medical Center between 1 1 March 2020 and 15 November 2020 in Atlanta, Georgia were included. We performed multivariable logistic regression to determine demographic and clinical factors associated with COVID-19 hospitalization overall and stratified by age less than 50 and at least 50 years. RESULTS: Three hundred and sixty-five PWH (mean age 49 years, 74% cisgender male, 82% black) were included. Ninety-six percent were on antiretroviral therapy (ART), 87% had CD4 + T-cell count at least 200 cells/µl, and 89% had HIV-1 RNA less than 200 copies/ml. Overall, age [adjusted odds ratio (aOR) 95% confidence interval (CI) 1.07 (1.04-1.10)], later date of SARS-CoV-2 infection [aOR 0.997 (0.995-1.00)], heart disease [aOR 2.27 (1.06-4.85)], and history of hepatitis C virus (HCV) [aOR 2.59 (1.13-5.89)] were associated with COVID-19 hospitalization. Age-adjusted comorbidity burden was associated with 30% increased risk of hospitalization [aOR 1.30 (1.11-1.54)]. Among 168 PWH less than 50 years old, older age [aOR 1.09 (1.01-1.18)] and no ART use [aOR 40.26 (4.12-393.62)] were associated with hospitalization; age-adjusted comorbidity burden was not ( P  = 0.25). Among 197 PWH at least 50, older age [aOR 1.10 (1.04-1.16)], heart disease [aOR 2.45 (1.04-5.77)], history of HCV [aOR 3.52 (1.29-9.60)], and age-adjusted comorbidity burden [aOR 1.36 (1.12-1.66)] were associated with hospitalization. CONCLUSION: Comorbidity burden is more strongly associated with COVID-19 hospitalization among older, rather than younger, PWH. These findings may have important implications for risk-stratifying COVID-19 therapies and booster recommendations in PWH.

The Association Between HIV Status, Estradiol, and Sex Hormone Binding Globulin Among Premenopausal Women in the Women's Interagency HIV Study.

Background: Characterizing estradiol among women with HIV may have implications for breast cancer and cardiovascular disease risk but has not been adequately explored. We quantified differences in total (E2), free (FE2) estradiol, and sex hormone binding globulin (SHBG) by HIV and viral suppression status. Methods: Women from a substudy (2003-2006) within the Women's Interagency HIV Study (IRB approved at each participating site) were included if they reported: a period in the last six months, were not pregnant/breastfeeding, no oophorectomy, and no exogenous hormone use in the prior year. Serum was collected on days 2-4 of the menstrual cycle. We assessed differences in biomarkers at 25th, 50th, and 75th percentiles by HIV and viral suppression status using weighted quantile regression. Results: Among 643 women (68% with HIV) median age was 37 years. All E2 percentiles were significantly (p < 0.05) lower in women with suppressed viral load versus women without HIV (4-10 pg/mL). The 25th and 50th percentile of E2 were 4-5 pg/mL lower in women with unsuppressed viral load compared to women without HIV (p < 0.05). The 25th and 50th percentile of SHBG was significantly higher in women with unsuppressed viral load compared to women without HIV (10 and 12 nmol/L, respectively). There were no consistent differences in estradiol or SHBG by suppression status. Conclusions: There were no differences in FE2 but significantly lower E2 and higher SHBG among women with HIV versus without HIV. Further research is merited in a large contemporary sample to clarify the clinical implications of these findings.

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.

Patient Experiences with Telemedicine for HIV Care During the First COVID-19 Wave in Atlanta, Georgia.

We explored experiences with telemedicine among persons with HIV (PWH) during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. A convenience sample of adults (>18 years) receiving care in an urban clinic in Atlanta were invited to participate. Patients completed a structured survey that assessed the usefulness, quality, satisfaction, and concerns with telemedicine services (telephone calls) received during the first wave of the COVID-19 pandemic (March-May 2020). Demographic, plasma HIV-1 RNA, and CD4+ T cell count data were obtained through medical chart abstraction. Bootstrapped t-tests and chi-square tests were used to examine differences in patient experiences by age, sex, and race. Of 406 PWH contacted, 101 completed the survey (median age 55 years, 84% men, 77% Black, 98% virally suppressed, median CD4 count 572 cells/µL). The main HIV care disruptions experienced were delays in follow-up visits (40%), difficulty getting viral load measured (35%), and difficulty accessing antiretroviral therapy (21%). Participant ratings for quality (median score 6.5/7), usefulness (median score 6.0/7), and satisfaction (median score 6.3/7) with telemedicine were high. However, 28% of patients expressed concerns about providers' ability to examine them and about the lack of laboratory tests. More women had concerns about providers' ability to examine them (92% vs. 50%, p = .005) and about the safety of their personal information (69% vs. 23%, p = .002) compared with men. No age or race differences were observed. Although PWH are generally satisfied with telephone-based telemedicine, concerns with its use were notable, particularly among women. Future HIV telemedicine models should address these.

Clinical and procedural characteristics of persons living with HIV presenting with acute coronary syndrome.

OBJECTIVES: Persons living with HIV (PLWH) are at greater risk for acute coronary syndrome (ACS). Practice patterns of ACS management by HIV serostatus are unknown. We examined the presentation and management of ACS in PLWH. DESIGN: Retrospective case-control study. METHODS: We included 86 PLWH and 263 sex-matched and race-matched HIV-negative controls hospitalized with ACS between 2004 and 2013. We performed multivariable conditional logistic regression to determine the associations between HIV serostatus and ACS type and management. RESULTS: Both groups were predominantly of black race and male sex. PLWH were significantly younger (53 vs. 60 years) and more likely to smoke (48 vs. 31%). Among PLWH, 30% had CD4 cell count less than 200 cells/µl and 58% had undetectable HIV RNA. PLWH had more single-vessel disease and a higher median Gensini score among those with single-vessel disease (32 vs. 4.25) than controls. HIV serostatus was positively associated with ST-elevation myocardial infarction (STEMI) [adjusted odds ratio (aOR) (95% confidence interval (CI)):5.05 (1.82-14.02)], and any revascularization procedure after ACS [aOR (95% CI): 2.90 (1.01-8.39)] and negatively associated with non-STEMI [aOR (95% CI): 0.33 (0.14-0.79)] presentation. PLWH who underwent stent placement had a higher likelihood of bare metal stent placement compared with controls [70 vs. 15%, aOR (95% CI): 5.94 (1.33-26.55)]. Among PLWH, ACS characteristics were not significantly associated with CD4 cell count, HIV RNA, or antiretroviral therapy. CONCLUSION: PLWH hospitalized with ACS were more likely to have severe single-vessel disease, present with STEMI rather than non-STEMI, and undergo revascularization, and less likely to have a drug-eluting stent placed than matched HIV-negative controls, suggesting that coronary plaque morphology and/or distribution is different with HIV infection and warrants further investigation.

Clinical characteristics, comorbidities and outcomes among persons with HIV hospitalized with coronavirus disease 2019 in Atlanta, Georgia.

BACKGROUND: There are limited data describing the presenting characteristics and outcomes among US persons with HIV (PWH) requiring hospitalization for coronavirus disease 2019 (COVID-19). METHODS: We performed a case series of all PWH sequentially admitted with COVID-19 from 8 March 2020 to 23 April 2020 at three hospitals in Atlanta, Georgia. Sociodemographic, clinical and HIV-associated characteristics were collected. RESULTS: Of 530 confirmed COVID-19 cases hospitalized during this period, 20 occurred among PWH (3.8%). The median age was 57 (Q1-Q3, 48-62) years, 65% were men, and 85% were non-Hispanic Black. Presenting median symptom duration was 5 (Q1-Q3, 3-7) days; cough (90%), fever (65%), malaise (60%) and dyspnea (60%) were most common. On admission, 40% of patients required oxygenation support and 65% had an abnormal chest radiograph. Median length of hospitalization was 5 (Q1-Q3, 4-12) days, 30% required intensive care, 15% required intubation, and 15% died. Median CD4 cell count prior to admission was 425 (Q1-Q3, 262-815) cells/µl and 90% of patients had HIV-1 RNA less than 200 copies/ml. Half of the patients had at least five comorbidities; hypertension (70%), dyslipidemia (60%) and diabetes (45%) were most prevalent. All three patients who died had CD4 cell count more than 200, HIV suppression and each had a total of five comorbidities. CONCLUSION: The multisite series in the Southern United States provides characteristics and early outcomes of hospitalized PWH with COVID-19. Nearly all patients had controlled HIV and a high comorbidity burden. Additional study of COVID-19 among PWH is needed to determine the role of age, comorbidities and HIV control in mediating COVID-19 presentation and its sequelae.

The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women.

OBJECTIVE: HIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV. DESIGN: Retrospective cohort study. METHODS: A total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status. RESULTS: Median (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 µm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 µm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction). CONCLUSION: In our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

Bone Loss in HIV Infection.

Human immunodeficiency virus (HIV) infection is an established risk factor for low bone mineral density (BMD) and subsequent fracture, and treatment with combination antiretroviral therapy (cART) leads to additional BMD loss, particularly in the first 1-2 years of therapy. The prevalence of low BMD and fragility fracture is expected to increase as the HIV-infected population ages with successful treatment with cART. Mechanisms of bone loss in the setting of HIV infection are likely multifactorial, and include viral, host, and immune effects, as well as direct and indirect effects of cART, particularly tenofovir disoproxil fumarate (TDF) and the protease inhibitors (PIs). Emerging data indicate that BMD loss following cART initiation can be mitigated by prophylaxis with either long-acting bisphosphonates or vitamin D and calcium supplementation. In addition, newer antiretrovirals, particularly the integrase strand transfer inhibitors and tenofovir alafenamide (TAF), are associated with less intense bone loss than PIs and TDF. However, further studies are needed to establish optimal bone sparing cART regimens, appropriate screening intervals, and preventive measures to address the rising prevalence of fragility bone disease in the HIV population.

The protease inhibitors and HIV-associated bone loss.

PURPOSE OF REVIEW: HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2-6% bone mineral density (BMD) loss within the first 1-2 years of therapy. Although tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PIs), have adverse bone effects. In the current review, we examine bone loss associated with protease inhibitor use, describing the relative magnitude of bone loss reported for individual protease inhibitors. We also review the potential mechanisms associated with protease inhibitor-induced bone loss. RECENT FINDINGS: As a class, protease inhibitors contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in protease inhibitor-mediated bone loss in addition to plausible direct effects of protease inhibitors on bone cells. SUMMARY: Protease inhibitors remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population.