Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States.

BACKGROUND: Data on the effectiveness and safety of dolutegravir-based antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy as compared with other ART regimens commonly used in the United States and Europe, particularly when initiated before conception, are limited. METHODS: We conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat. Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non-dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results. RESULTS: Of the pregnancies in the study, 120 were in participants who received dolutegravir, 464 in those who received atazanavir-ritonavir, 185 in those who received darunavir-ritonavir, 243 in those who received rilpivirine, 86 in those who received raltegravir, and 159 in those who received elvitegravir-cobicistat. The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception. Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs. dolutegravir, -13.0 percentage points [95% confidence interval {CI}, -17.0 to -6.1], -17.0 percentage points [95% CI, -27.0 to -2.4], and -7.0 percentage points [95% CI, -13.3 to -0.0], respectively). The observed risks of preterm birth were 13.6 to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between non-dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar. CONCLUSIONS: Atazanavir-ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non-dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV.

BACKGROUND: The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. METHODS: We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging-epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation-estimated telomere length-and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. RESULTS: This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs -1.88 ± 5.07; P < .001) and lower DNA methylation-estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. CONCLUSIONS: Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.

Healthy dynamics of CD4 T cells may drive HIV resurgence in perinatally-infected infants on antiretroviral therapy.

In 2019 there were 490,000 children under five living with HIV. Understanding the dynamics of HIV suppression and rebound in this age group is crucial to optimizing treatment strategies and increasing the likelihood of infants achieving and sustaining viral suppression. Here we studied data from a cohort of 122 perinatally-infected infants who initiated antiretroviral treatment (ART) early after birth and were followed for up to four years. These data included longitudinal measurements of viral load (VL) and CD4 T cell numbers, together with information regarding treatment adherence. We previously showed that the dynamics of HIV decline in 53 of these infants who suppressed VL within one year were similar to those in adults. However, in extending our analysis to all 122 infants, we find that a deterministic model of HIV infection in adults cannot explain the full diversity in infant trajectories. We therefore adapt this model to include imperfect ART adherence and natural CD4 T cell decline and reconstitution processes in infants. We find that individual variation in both processes must be included to obtain the best fits. We also find that infants with faster rates of CD4 reconstitution on ART were more likely to experience resurgences in VL. Overall, our findings highlight the importance of combining mathematical modeling with clinical data to disentangle the role of natural immune processes and viral dynamics during HIV infection.

Growth Trajectories Over the First Year of Life Among Early-Treated Infants with Human Immunodeficiency Virus and Infants Who are Human Immunodeficiency Virus-Exposed Uninfected.

OBJECTIVE: To investigate the role of early antiretroviral therapy (ART) on growth trajectories of infants with human immunodeficiency virus (IHIV) in the first year of life. STUDY DESIGN: As part of a clinical trial of early ART in Johannesburg, South Africa (2015-2018), 116 IHIV diagnosed within 48 hours of birth were started on ART as soon as possible, and 80 uninfected infants born to mothers living with HIV (IHEU) were enrolled. Both groups were followed prospectively from birth through 48 weeks and growth parameters collected. The groups were compared and risk factors for poor growth investigated, in the full cohort and among IHIV separately. RESULTS: IHIV had lower mean weight-for-age Z-scores (WAZ) than IHEU at 4 and 8 weeks (-1.17 [SE:0.14] vs -0.72 [0.14], P = .035 and -1.23 [0.15] vs -0.67 [0.14], P = .012). Although there was some closing of the gap over time, means remained lower in IHIV through 48 weeks. In length-for-age Z-scores (LAZ), differences widened over time and IHIV had lower Z-scores by 48 weeks (-1.41 [0.15] vs -0.80 [0.18], P = .011). Deficits in WAZ and LAZ in IHIV vs IHEU were most marked among girls. IHIV with pre-ART viral load ≥1000 copies/ml had significantly lower weight-for-length and mid-upper arm circumference Z-scores across all time points through 48 weeks. CONCLUSIONS: IHIV on early ART had deficits in WAZ over the first 8 weeks of life and lower LAZ at 48 weeks than IHEU. Among IHIV, higher pre-ART viral load was associated with worse anthropometric indicators through 48 weeks.

Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

BACKGROUND: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU). METHODS: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders. RESULTS: Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months. CONCLUSIONS: Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review.

OBJECTIVES: The advent of antiretroviral therapy (ART) has reduced AIDS-related morbidity and mortality among people living with HIV (PLWH). Due to increased survival, PLWH have now been found to be at risk of chronic conditions related to ageing, such as cardiovascular disease (CVD). Hypertension is common in PLWH and is a major risk factor for the development of CVD. We conducted a systematic literature review to evaluate the research evidence on longitudinal blood pressure (BP) trajectories following ART initiation in PLWH. METHODS: We searched the following databases: PubMed, CINHAL, Scopus, and Web of Science (up to 15 March 2021) for peer-reviewed published studies that reported BP trajectories following ART initiation in PLWH. Three reviewers independently screened all studies by title and abstract. We included articles in English, published up to March 2021, that report office BP trajectories in PLWH initiating ART. A total of 10 publications met our inclusion criteria. Eight studies were prospective cohorts and two were retrospective. RESULTS: Nine out of 10 studies in the literature reported an increase in systolic BP (4.7-10.0 mmHg in studies with a follow-up range of 6 months to 8 years, and 3.0-4.7 mmHg/year in time-averaged studies). In addition, four out of 10 studies reported increases in diastolic BP (2.3-8.0 mmHg for a 6 month to 6.8-year follow-up range and 2.3 mmHg/year). CONCLUSION: Systolic BP consistently increases while diastolic BP changes are more heterogeneous following ART initiation in PLWH. However, the studies were highly variable with respect to population demographics, ART regimen and duration, and follow-up time. Nevertheless, given the risks of CVD complications, such as stroke, heart failure and myocardial infarction, associated with elevated BP, results highlight the importance of future research in this area. It will be important to better characterize BP trajectories over time, identify the most critical times for interventions to reduce BP, determine the long-term CVD consequences in PLWH with elevated BP, and understand how different ART regimens may or may not influence BP and CVD disease.

Clinical characteristics of pregnancy and lactation associated osteoporosis: An online survey study.

Pregnancy and lactation associated osteoporosis is a rare and often severe osteoporosis presentation. Little information is available about etiology, clinical characteristics, risk factors and predictors of severity. Using an anonymized questionnaire, we defined clinical characteristics and potential risk factors for disease severity in PLO including primiparity, heparin exposure and celiac disease. PURPOSE: Pregnancy and lactation associated osteoporosis (PLO) is a rare form of early-onset osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. Little information is available about etiology, clinical characteristics, risk factors and predictors of disease severity. METHODS: PLO patients were recruited to complete an anonymized online questionnaire. Disease severity was defined as total number of fractures during or after the first pregnancy associated with a fracture(s). Analyses related disease severity to potential predictors including diseases/conditions or medication exposures. RESULTS: 177 completed surveys were received between 5/29/2018 and 1/12/2022. Average age at initial PLO fracture event was 32 ± 5 years. The majority were primiparous with singleton pregnancy and 79% fractured during lactation. Subjects reported 4.7 ± 2.7 total PLO fractures, with 48% reporting ≥ 5 fractures. Vertebral fractures, reported by 164/177 responders (93%), were the most common fracture type. Conditions and medications most commonly reported included vitamin D deficiency, amenorrhea unrelated to pregnancy, nephrolithiasis, celiac disease (CD), oral steroid use, heparin products during pregnancy and progestin only contraceptive after pregnancy. CD and heparins exposure during pregnancy were significantly related to disease severity. CONCLUSION: This is the largest study characterizing clinical features of PLO to date. The large number of participants and broad range of clinical and fracture characteristics queried has yielded novel information on the characteristics of PLO and potential risk factors for its severity, including primiparity, exposure to heparin and CD. These findings provide important preliminary data that can help target future mechanistic investigations.

Body Composition Trajectories During the First 23 Months of Life Differ by HIV Exposure Among Infants in Western Kenya: A Prospective Study.

BACKGROUND: Infants who are HIV-exposed and uninfected have suboptimal growth patterns compared to those who are HIV-unexposed and uninfected. However, little is known about how these patterns persist beyond 1 year of life. OBJECTIVES: This study aimed to examine whether infant body composition and growth trajectories differed by HIV exposure during the first 2 years of life among Kenyan infants using advanced growth modeling. METHODS: Repeated infant body composition and growth measurements (mean: 6; range: 2-7) were obtained from 6 weeks to 23 months in the Pith Moromo cohort in Western Kenya (n = 295, 50% HIV-exposed and uninfected, 50% male). Body composition trajectory groups were fitted using latent class mixed modeling (LCMM) and associations between HIV exposure and growth trajectories were examined using logistic regression analysis. RESULTS: All infants exhibited poor growth. However, HIV-exposed infants generally grew suboptimally than unexposed infants. Across all body composition models except for the sum of skinfolds, HIV-exposed infants had a higher likelihood of belonging to the suboptimal growth groups identified by LCMM than the HIV-unexposed infants. Notably, HIV-exposed infants were 3.3 times more likely (95% CI: 1.5-7.4) to belong to the length-for-age z-score growth class that remained at a z-score of < -2, indicating stunted growth. HIV-exposed infants were also 2.6 times more likely (95% CI: 1.2-5.4) to belong to the weight-for-length-for-age z-score growth class that remained between 0 and -1, and were 4.2 times more likely (95% CI: 1.9-9.3) to belong to the weight-for-age z-score growth class that indicated poor weight gain besides stunted linear growth. CONCLUSIONS: In a cohort of Kenyan infants, HIV-exposed infants grew suboptimally compared to HIV-unexposed infants beyond 1 year of age. These growth patterns and longer-term effects should be further investigated to support the ongoing efforts to reduce early-life HIV exposure-related health disparities.

Information, Motivation and Behavioral Skills as Mediators Between Sexual Minority Stigma and Condomless anal Sex Among Black South African Men Who have Sex with Men.

We assessed pathways between sexual minority stigma and condomless anal intercourse (CAI) among two samples of Black South African men who have sex with other men (MSM). Two cross-sectional surveys were conducted in Tshwane, South Africa; one among 199 Black MSM and another among 480 Black MSM. Men reported on external and internalized experiences of sexual minority stigma, mental health, alcohol use, information-motivation-behavioral skills (IMB) model constructs, and CAI. Structural equation modeling was used to test whether external and internalized stigma were directly and indirectly associated with CAI. In both studies, external stigma and internalized stigma were associated with CAI through IMB model constructs. These results suggest a pathway through which stigma contributes to HIV risk. For HIV prevention efforts to be effective, strengthening safer sex motivation and thus decreasing sexual risk behavior likely requires reducing sexual minority stigma that MSM experience and internalize.

Disclosure to South African children about their own HIV status over time.

Disclosure to children living with HIV (CLHIV) about their own status is associated with positive outcomes such as treatment adherence, but prior cross-sectional studies in sub-Saharan Africa report disclosure rates of <50%. This study aims to assess pediatric disclosure over time. 548 CLHIV were followed from 2/2013-4/2018 in Johannesburg, South Africa. Cumulative incidence of disclosure was calculated with Kaplan-Meier analysis, and disclosure characteristics assessed with a Cox model. By end of follow-up, cumulative disclosure was 70.3% (95% confidence interval: 60.0-79.9). Median age at disclosure was 9 years (range: 3-13). Baseline predictors of disclosure included older child age and the child having a history of going hungry. Prior to disclosure, 98.0% of caregivers who disclosed had conversed with their child about their illness or an HIV-related topic, or their child had asked about HIV, versus 88.6% of caregivers who never disclosed. While many children did not receive disclosure during this relatively large, longitudinal study of South African CLHIV, caregivers who had not yet disclosed may have been preparing to do so by discussing their child's health or HIV generally with their child. This highlights the need for clinicians to consistently support caregivers throughout the incremental disclosure process.

Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants.

BACKGROUND: Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described. METHODS: Sixty-three neonates diagnosed with HIV-1 <48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible. Fifty-nine (94%) infants received nevirapine prophylaxis from birth until ART start. Viably preserved peripheral blood mononuclear cells (PBMCs) collected at regular intervals to 48 weeks, and from mothers at enrollment, were tested using integrase-targeted, semi-nested, real-time quantitative hydrolysis probe (TaqMan) PCR assays to quantify total HIV-1 subtype C viral DNA (vDNA). Predictors were investigated using generalized estimating equation regression. RESULTS: Thirty-one (49.2%) infants initiated ART <48 hours, 24 (38.1%) <14 days, and 8 (12.7%) >14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART were associated with lower vDNA in the first 48 weeks after ART start. No antenatal maternal ART and breastfeeding were also associated with lower vDNA. Older age at ART initiation had a discernible negative impact when initiated >14 days. CONCLUSIONS: Among very early treated infants, higher CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART, infection occurring in the absence of maternal antenatal ART, and breastfeeding were associated with lower levels of HIV-1 DNA in the first 48 weeks of treatment. Clinical Trials Registration. clinicaltrials.gov (NCT02431975).

Teaching Health Equity in the Time of COVID-19: a Virtual Look Through the Lens of Structural Racism.

INTRODUCTION: In the context of marked health disparities affecting historically marginalized communities, medical schools have an obligation to rapidly scale up COVID-19 education through the lens of structural racism. AIM: To develop and implement a virtual curriculum on structural racism in a required COVID-19 course for medical students using "just-in-time" training. SETTING: Academic medical institution during the height of COVID-19 in the spring of 2020. PARTICIPANTS: Three hundred ninety-three 3rd and 4th-year medical students prior to re-entry into clinical care. PROGRAM DESCRIPTION: Three educational sessions focused on (1) racial health disparities, (2) othering and pandemics, and (3) frameworks to address health inequity. The virtual teaching methods included narrated recorded presentations, reflections, and student-facilitated small group dialogue. PROGRAM EVALUATION: In matched pre- and post-surveys, participants reported significant changes in their confidence in achieving the learning objectives and high satisfaction with small group peer facilitation. DISCUSSION: The use of "just-in-time" training exploring the intersection between COVID-19 and structural racism facilitated the delivery of time-relevant and immediately clinically applicable content as students were preparing to re-enter a transformed clinical space. Similar approaches can be employed to adapt to changing healthcare landscapes as academic medical centers strive to build more equitable health systems.

Assessing the Information-Motivation-Behavioral Skills Model to Predict Pre-exposure Prophylaxis Adherence Among Black Men Who have Sex with Men and Transgender Women in a Community Setting in New York City.

The Information-Motivation-Behavioral Skills (IMB) Model has been used to understand adherence to medications and intentions to uptake pre-exposure prophylaxis (PrEP) to prevent HIV infection. In the current study, the IMB Model was used to understand factors that predict adherence to PrEP among a community-based cohort of 204 Black men who have sex with men (MSM) and transgender women (TGW) using structural equation modeling. PrEP motivation was directly associated with PrEP behavioral skills (ß = 0.320, p = 0.009), and PrEP behavioral skills were directly associated with PrEP adherence (ß = 0.416, p = 0.001). PrEP knowledge and PrEP motivation were not associated with PrEP adherence, directly or indirectly. The analysis identified intervenable factors that predicted PrEP adherence. Screening for motivation and behavioral skills could be used to identify where additional support to improve PrEP adherence is needed, or whether to offer alternative PrEP modalities or delivery strategies.

RESUMEN: El Modelo de Información-Motivación-Habilidades Conductuales (IMB) ha sido utilizado para comprender la adherencia a los medicamentos y la intención de tomar la profilaxis pre-exposición (PrEP) para prevenir la infección por el VIH. En el estudio actual, se usó el modelo IMB para comprender los factores que predicen la adherencia a la PrEP entre una cohorte reclutada en la comunidad de 204 hombres que tienen sexo con hombres (HSH) y mujeres transgénero (TGW) de raza negra, usando modelos de ecuaciones estructurales. La motivación de adherir a la PrEP se asoció directamente con las habilidades conductuales de la PrEP adherencia (ß = 0.320, p = 0.009), y las habilidades conductuales de la PrEP adherencia se asociaron directamente con la adherencia a la PrEP (ß = 0.416, p = 0.001). El conocimiento de PrEP y la motivación de adherir a la PrEPno se asociaron con la adherencia a la PrEP, ni directa o indirectamente. El análisis identificó factores intervenibles que predijeron la adherencia a la PrEP. La evaluación de la motivación de adherir a la PrEP y las habilidades conductuales de la PrEP adherencia podría ser usado para identificar situaciones en que se necesita apoyo adicional para mejorar la adherencia a la PrEP, o si se deben ofrecer modalidades alternativas de recibir PrEP o estrategias alternativas para entregar PrEP.

RT-PCR negative COVID-19.

BACKGROUND: COVID-19 is a multi-system infection with emerging evidence-based antiviral and anti-inflammatory therapies to improve disease prognosis. However, a subset of patients with COVID-19 signs and symptoms have repeatedly negative RT-PCR tests, leading to treatment hesitancy. We used comparative serology early in the COVID-19 pandemic when background seroprevalence was low to estimate the likelihood of COVID-19 infection among RT-PCR negative patients with clinical signs and/or symptoms compatible with COVID-19. METHODS: Between April and October 2020, we conducted serologic testing of patients with (i) signs and symptoms of COVID-19 who were repeatedly negative by RT-PCR ('Probables'; N = 20), (ii) signs and symptoms of COVID-19 but with a potential alternative diagnosis ('Suspects'; N = 15), (iii) no signs and symptoms of COVID-19 ('Non-suspects'; N = 43), (iv) RT-PCR confirmed COVID-19 patients (N = 40), and (v) pre-pandemic samples (N = 55). RESULTS: Probables had similar seropositivity and levels of IgG and IgM antibodies as propensity-score matched RT-PCR confirmed COVID-19 patients (60.0% vs 80.0% for IgG, p-value = 0.13; 50.0% vs 72.5% for IgM, p-value = 0.10), but multi-fold higher seropositivity rates than Suspects and matched Non-suspects (60.0% vs 13.3% and 11.6% for IgG; 50.0% vs 0% and 4.7% for IgM respectively; p-values < 0.01). However, Probables were half as likely to receive COVID-19 treatment than the RT-PCR confirmed COVID-19 patients with similar disease severity. CONCLUSIONS: Findings from this study indicate a high likelihood of acute COVID-19 among RT-PCR negative with typical signs/symptoms, but a common omission of COVID-19 therapies among these patients. Clinically diagnosed COVID-19, independent of RT-PCR positivity, thus has a potential vital role in guiding treatment decisions.

Intelligent Pandemic Surveillance via Privacy-Preserving Crowdsensing.

Intelligently responding to a pandemic like Covid-19 requires sophisticated models over accurate real-time data, which is typically lacking at the start, e.g., due to deficient population testing. In such times, crowdsensing of spatially tagged disease-related symptoms provides an alternative way of acquiring real-time insights about the pandemic. Existing crowdsensing systems aggregate and release data for pre-fixed regions, e.g., counties. However, the insights obtained from such aggregates do not provide useful information about smaller regions - e.g., neighborhoods where outbreaks typically occur - and the aggregate-and-release method is vulnerable to privacy attacks. Therefore, we propose a novel differentially private method to obtain accurate insights from crowdsensed data for any number of regions specified by the users (e.g., researchers and a policy makers) without compromising privacy of the data contributors. Our approach, which has been implemented and deployed, informs the development of the future privacy-preserving intelligent systems for longitudinal and spatial data analytics.

Epigenetic Aging Biomarkers Associated With Cognitive Impairment in Older African American Adults With Human Immunodeficiency Virus (HIV).

BACKGROUND: Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with human immunodeficiency virus (HIV, PWH), but limited data are available among African Americans (AA), women, and older PWH. METHODS: DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The National Institutes of Health (NIH) Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria. RESULTS: The PWH and control groups did not differ by sex, chronological age, or ethnicity. In total, 83% of PWH had a viral load <50 copies/mL, and 94% had a recent CD4 ≥200 cells/µL. The PWH group had a higher EAA, EEAA, GrimAge, and PhenoAge, and a lower DNAm-TL compared to the controls. IEAA was not different between groups. For PWH, there were significant negative correlations between IEAA and executive function, attention, and working memory and PhenoAge and attention. No associations between biomarkers and frailty were detected. CONCLUSIONS: Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type National Institutes of Health composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.

Risk Factors and Outcomes of Hospitalized Patients With Severe Coronavirus Disease 2019 (COVID-19) and Secondary Bloodstream Infections: A Multicenter Case-Control Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic. Clinical characteristics regarding secondary infections in patients with COVID-19 have been reported, but detailed microbiology, risk factors, and outcomes of secondary bloodstream infections (sBSIs) in patients with severe COVID-19 have not been well described. METHODS: We performed a multicenter case-control study including all hospitalized patients diagnosed with severe COVID-19 and blood cultures drawn from 1 March 2020 to 7 May 2020 at 3 academic medical centers in New Jersey. Data collection included demographics, clinical and microbiologic variables, and patient outcomes. Risk factors and outcomes were compared between cases (sBSI) and controls (no sBSI). RESULTS: A total of 375 hospitalized patients were included. There were 128 sBSIs during the hospitalization. For the first set of positive blood cultures, 117 (91.4%) were bacterial and 7 (5.5%) were fungal. Those with sBSI were more likely to have altered mental status, lower mean percentage oxygen saturation on room air, have septic shock, and be admitted to the intensive care unit compared with controls. In-hospital mortality was higher in those with an sBSI versus controls (53.1% vs 32.8%, P = .0001). CONCLUSIONS: We observed that hospitalized adult patients with severe COVID-19 and sBSI had a more severe initial presentation, prolonged hospital course, and worse clinical outcomes. To maintain antimicrobial stewardship principles, further prospective studies are necessary to better characterize risk factors and prediction modeling to better understand when to suspect and empirically treat for sBSIs in severe COVID-19.

Components of metabolic syndrome associated with lower neurocognitive performance in youth with perinatally acquired HIV and youth who are HIV-exposed uninfected.

We investigated the association of metabolic syndrome (MetS) and its components [abdominal obesity, elevated triglycerides (TG), low HDL cholesterol, elevated blood pressure (BP), and impaired fasting glycemia (IFG)] with neurocognitive impairment in youth with perinatally acquired HIV (YPHIV) or who are perinatally HIV-exposed uninfected (YPHEU). This was an observational study with a comparison group of 350 YPHIV and 68 YPHEU ages 10-19 years. Youth with MetS components measured between 1 year before and 3 months after a baseline neurocognitive assessment (Wechsler Intelligence Scale) were selected from the Pediatric HIV/AIDS Cohort Study (PHACS). A sub-group completed another assessment 3 years later. We assessed the association of each baseline MetS component with five standardized neurocognitive indices at baseline and changes in indices over time. At baseline, 15% of YPHIV and 18% of YPHEU met criteria for ≥ 2 MetS components. Among YPHIV, there was no association between MetS components and neurocognitive indices at baseline; however, over time, elevated baseline BP was associated with a greater decrease in mean Perceptual Reasoning scores (-4.3;95%CI: -8.8,0.3) and ≥ 2 MetS components with a greater decrease in mean Processing Speed scores (-5.1;95%CI: -9.4, -0.8). Among YPHEU, elevated TG was associated with lower mean Verbal Comprehension, Perceptual Reasoning, and Full-scale IQ scores at baseline, and IFG with lower mean Verbal Comprehension scores. Components of MetS in YPHIV (elevated BP) and YPHEU (elevated TG and IFG) were associated with lower neurocognitive performance index scores. Studies to elucidate how modifying metabolic risk factors early in life may improve neurocognitive outcomes in this population are warranted.

Systematic review: fetal death reporting and risk in Zika-affected pregnancies.

OBJECTIVES: Zika virus is linked to several adverse pregnancy outcomes. We assessed whether Zika infection during pregnancy is associated with increased risk of foetal death (miscarriage, stillbirth, abortion) and whether there is incomplete reporting of such deaths. METHODS: We searched PubMed, Embase, CINAHL, Web of Science and LILACS for studies reporting Zika-affected completed pregnancies (ending in foetal death or live birth), excluding studies whose aim required live birth. Studies 'allowed' foetal death if their populations were defined to encompass both live births and foetal deaths, regardless of whether deaths were actually found. Two authors independently extracted data and assessed study quality. Foetal death absolute and relative risks in Zika-affected vs. unaffected pregnancies were calculated. RESULTS: We found 108 reports including 24 699 completed, Zika-affected pregnancies. The median absolute risk in 37 studies of completed, Zika-affected pregnancies was 6.3% (IQR 3.2%, 10.6%) for foetal death and 5.9% (IQR 0%, 29.1%) for non-fatal adverse outcomes (e.g. microcephaly). More studies allowed non-fatal adverse outcomes (95%) than foetal death (58%). Of studies which allowed them, 94% found at least one foetal death. In 37% of reports, it was unknown whether foetal deaths were allowed. Only one study had sufficient data to estimate a foetal death relative risk (11.05, 95% CI 3.43, 35.55). CONCLUSIONS: Evidence was insufficient to determine whether foetal death risk is higher in Zika-affected pregnancies, but suggests quality of foetal death reporting should be improved, including stating whether foetal deaths were found, how many, and at what gestational ages, or justifying their exclusion.

OBJECTIFS: Le virus Zika est lié à plusieurs issues défavorables de la grossesse. Nous avons évalué si l'infection à Zika pendant la grossesse était associée à un risque accru de mort fœtale (fausse couche, mortinaissance, avortement) et s'il y avait une déclaration incomplète de ces décès. MÉTHODES: Nous avons recherché dans PubMed, EMBASE, Cinahl, Web of Science et LILACS des études rapportant des grossesses terminées touchées par le virus Zika (se terminant par une mort fœtale ou une naissance vivante), à l'exclusion des études dont l'objectif nécessitait une naissance vivante. Les études «autorisaient¼ la mort fœtale si leur population était définie comme englobant à la fois les naissances vivantes et les décès fœtaux, indépendamment du fait que des décès aient été effectivement constatés. Deux auteurs ont indépendamment extrait les données et évalué la qualité des études. Les risques absolus et relatifs de mortalité fœtale dans les grossesses affectées par Zika par rapport aux grossesses non affectées ont été calculés. RÉSULTATS: Nous avons trouvé 108 reports dont 24.699 grossesses terminées et affectées par le virus Zika. Le risque médian absolu dans 37 études portant sur des grossesses terminées affectées par Zika était de 6,3% (IQR 3,2%, 10,6%) pour la mort fœtale et de 5,9% (IQR 0%, 29,1%) pour les issues indésirables non mortelles (par exemple microcéphalie). Plus d'études ont «autorisé¼ des résultats indésirables non mortels (95%) que la mort fœtale (58%). Parmi les études qui les ont «autorisé¼, 94% ont trouvé au moins un décès fœtal. Dans 37% des rapports, il n'est pas indiqué si la mort fœtale avait été «autorisée¼. Une seule étude contenait des données suffisantes pour estimer un risque relatif de mort fœtale (11,05 ; IC95%: 3,43, 35,55). CONCLUSIONS: Les données étaient insuffisantes pour déterminer si le risque de mort fœtale est plus élevé dans les grossesses touchées par le virus Zika, mais suggèrent que la qualité des reports sur les décès fœtaux devrait être améliorée, notamment en indiquant si des décès fœtaux ont été constatés, combien et à quel âge gestationnel, ou justifiant leur exclusion.

Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV.

OBJECTIVES: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority. METHODS: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens. RESULTS: The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV. CONCLUSIONS: South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals.