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.

Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022.

Background: We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022. Methods: We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID). Results: NMV/r uptake was 13.6% (95% CI, 11.9%-15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%-2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%-2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%-20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%-29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%-12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%-13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P = .001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%-70%) reported that NMV/r was helpful for reducing COVID-19 symptoms. Conclusions: Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed.

Seroincidence of SARS-CoV-2 infection prior to and during the rollout of vaccines in a community-based prospective cohort of U.S. adults.

This study used repeat serologic testing to estimate infection rates and risk factors in two overlapping cohorts of SARS-CoV-2 N protein seronegative U.S. adults. One mostly unvaccinated sub-cohort was tracked from April 2020 to March 2021 (pre-vaccine/wild-type era, n = 3421), and the other, mostly vaccinated cohort, from March 2021 to June 2022 (vaccine/variant era, n = 2735). Vaccine uptake was 0.53% and 91.3% in the pre-vaccine and vaccine/variant cohorts, respectively. Corresponding seroconversion rates were 9.6 and 25.7 per 100 person-years. In both cohorts, sociodemographic and epidemiologic risk factors for infection were similar, though new risk factors emerged in the vaccine/variant era, such as having a child in the household. Despite higher incidence rates in the vaccine/variant cohort, vaccine boosters, masking, and social distancing were associated with substantially reduced infection risk, even through major variant surges.

Pre-exposure prophylaxis uptake concerns in the Democratic Republic of the Congo: Key population and healthcare workers perspectives.

Key populations (KP) in the Democratic Republic of the Congo (DRC), including female sex workers (SW), are disproportionally affected by HIV. Quantitative feedback surveys were conducted at seven health facilities in DRC with 70 KP clients enrolled in pre-exposure prophylaxis (PrEP) services to measure benefits and concerns. The surveys also assessed satisfaction with PrEP services and experiences of stigma at the health facilities. Thirty healthcare workers (HCW) were surveyed to measure attitudes, beliefs, and acceptability of providing services to KP. KP client survey participants were primarily female SW. KP clients reported that the primary concern about taking PrEP was fear of side effects (67%) although few KP reported having experienced side effect (14%). HCW concurred with clients that experienced and anticipated side effects were a primary PrEP uptake concern, along with costs of clinic visits.

Safety, Efficacy, and Ill Intent: Examining COVID-19 Vaccine Perceptions among the New Undervaccinated Moveable Middle in a U.S. Cohort, October 2022.

Individuals who received their primary vaccine series only (with no subsequent booster) may be a new type of "moveable middle" given their receipt of the original COVID-19 vaccination. One population within the moveable middle for whom tailored interventions may be needed is individuals with common mental disorders (CMD). The purpose of this paper is to understand the vaccine perceptions among this new moveable middle-the undervaccinated-and within the undervaccinated to examine the extent to which COVID-19 vaccine perceptions and motivations differ among those with and without symptoms of CMD. Using data from the CHASING COVID Cohort, we examine the relationship between vaccination status, CMD, and vaccine perceptions in the undervaccinated. Among 510 undervaccinated participants who had completed the primary vaccine series but were not boosted, the most common reasons for undervaccination focused on efficacy (not seeing a need for an additional dose, 42.4%; there not being enough evidence that a booster dose is effective, 26.5%; already having had COVID-19, 19.6%). Other concerns were related to safety (long-term side effects, 21.0%; short-term side effects, 17.6%) and logistics (plan to get a booster but haven't had time yet, 18.8%). Overall, the greatest vaccine concerns (over 30%) for the undervaccinated focused on efficacy and safety issues. Symptoms of depression or anxiety were associated with lower levels of vaccine efficacy and greater safety concerns in adjusted models. The implications of our study are that campaigns that are hoping to maximize vaccination uptake should consider focusing on and emphasizing messaging on efficacy and safety issues.

The Importance of Incorporating At-Home Testing Into SARS-CoV-2 Point Prevalence Estimates: Findings From a US National Cohort, February 2022.

BACKGROUND: Passive, case-based surveillance underestimates the true extent of active infections in the population due to undiagnosed and untested cases, the exclusion of probable cases diagnosed point-of-care rapid antigen tests, and the exclusive use of at-home rapid tests which are not reported as part of case-based surveillance. The extent in which COVID-19 surveillance may be underestimating the burden of infection is likely due to time-varying factors such as decreased test-seeking behaviors and increased access to and availability of at-home testing. OBJECTIVE: The objective of this study is to estimate the prevalence of SARS-CoV-2 based on different definitions of a case to ascertain the extent to which cases of SARS-CoV-2 may be underestimated by case-based surveillance. METHODS: A survey on COVID-19 exposure, infection, and testing was administered to calculate point prevalence of SARS-CoV-2 among a diverse sample of cohort adults from February 8, 2022, to February 22, 2022. Three-point prevalence estimates were calculated among the cohort, as follows: (1) proportion positives based on polymerase chain reaction (PCR) and rapid antigen tests; (2) proportion positives based on testing exclusively with rapid at-home tests; and (3) proportion of probable undiagnosed cases. Test positivity and prevalence differences across booster status were also examined. RESULTS: Among a cohort of 4328, there were a total of 644 (14.9%) cases. The point prevalence estimate based on PCR or rapid antigen tests was 5.5% (95% CI 4.8%-6.2%), 3.7% (95% CI 3.1%-4.2%) based on at-home rapid tests, and 5.7% (95% CI 5.0%-6.4%) based on the case definition of a probable case. The total point prevalence across all definitions was 14.9% (95% CI 13.8%-16.0%). The percent positivity among PCR or rapid tests was 50.2%. No statistically significant differences were observed in prevalence between participants with a COVID-19 booster compared to fully vaccinated and nonboosted participants except among exclusive at-home rapid testers. CONCLUSIONS: Our findings suggest a substantial number of cases were missed by case-based surveillance systems during the Omicron B.1.1.529 surge, when at-home testing was common. Point prevalence surveys may be a rapid tool to be used to understand SARS-CoV-2 prevalence and would be especially important during case surges to measure the scope and spread of active infections in the population.

Comparison of quantitative ultrasonography and dual X-ray absorptiometry for bone status assessment in South African children living with HIV.

Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.

Reduction in Risk of Death Among Patients Admitted With COVID-19 Between the First and Second Epidemic Waves in New York City.

Background: Many regions have experienced successive epidemic waves of coronavirus disease 2019 (COVID-19) since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. Methods: We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-August 2020) and second (August 2020-March 2021) epidemic waves at an academic medical center in New York City. Results: Hospitalized patients (n = 4631) had lower overall and 30-day in-hospital mortality, defined as death or discharge to hospice, during the second wave (14% and 11%) than the first (22% and 21%). The wave 2 in-hospital mortality decrease persisted after adjusting for several potential confounders. Adjusting for the volume of COVID-19 admissions, a measure of health system strain, accounted for the mortality difference between waves. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave: SARS-CoV-2 cycle threshold, do-not-intubate status, oxygen requirement, and intensive care unit admission. Conclusions: This work suggests that the increased in-hospital mortality rates observed during the first epidemic wave were partly due to strain on hospital resources. Preparations for future epidemics should prioritize evidence-based patient risks, treatment paradigms, and approaches to augment hospital capacity.

Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City.

Many regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-June 2020) and second (December 2020-March 2021) epidemic waves at an academic medical center in New York City. Hospitalized patients (N=4631) had lower mortality during the second wave (14%) than the first (23%). Patients in the second wave had a lower 30-day mortality (Hazard Ratio (HR) 0.52, 95% CI 0.44, 0.61) than those in the first wave. The mortality decrease persisted after adjusting for confounders except for the volume of COVID-19 admissions (HR 0.88, 95% CI 0.70, 1.11), a measure of health system strain. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave. Article summary: Using clinical and demographic data from COVID-19 hospitalizations at a tertiary New York City medical center, we show that a reduction in mortality during the second epidemic wave was associated with decreased strain on healthcare resources.

Missed routine pediatric care and vaccinations in US children during the first year of the COVID-19 pandemic.

The COVID-19 pandemic has decreased uptake of pediatric preventive care, including immunizations. We estimate the prevalence of missed pediatric routine medical visits and vaccinations over the first year of the COVID-19 pandemic. We conducted a cross-sectional online survey of 2074 US parents of children ≤12 years in March 2021 to measure the proportion of children who missed pediatric care and vaccinations over the first 12 months of the COVID-19 pandemic. Poisson regression models were fitted to estimate adjusted prevalence ratios (aPR). All analyses were weighted to represent the target population. Overall, 41.3% (95%CI 38.3-43.8) of parents reported their youngest child missed a routine medical visit due to the COVID-19 pandemic. Missed care was more common among children ≥2 years compared to <2 years (aPR 1.82; 95%CI 1.47-2.26) and Hispanics compared to non-Hispanic Whites (aPR 1.31; 95%CI 1.14-1.51). A third of parents (33.1%; 95%CI 30.7-35.5) reported their child had missed a vaccination. Compared to the 2019-20 flu season, pediatric influenza vaccination decreased in 2020-21 (51.3% vs. 62.2%; p < 0.0001). A high proportion of US children ≤12 years missed routine pediatric care during the COVID-19 pandemic. Catch-up efforts are needed to ensure continuity of preventive care for all children.

COVID-19 Testing Among US Children, Parental Preferences for Testing Venues, and Acceptability of School-Based Testing.

OBJECTIVES: Testing remains critical for identifying pediatric cases of COVID-19 and as a public health intervention to contain infections. We surveyed US parents to measure the proportion of children tested for COVID-19 since the start of the pandemic, preferred testing venues for children, and acceptability of school-based COVID-19 testing. METHODS: We conducted an online survey of 2074 US parents of children aged ≤12 years in March 2021. We applied survey weights to generate national estimates, and we used Rao-Scott adjusted Pearson χ2 tests to compare incidence by selected sociodemographic characteristics. We used Poisson regression models with robust SEs to estimate adjusted risk ratios (aRRs) of pediatric testing. RESULTS: Among US parents, 35.9% reported their youngest child had ever been tested for COVID-19. Parents who were female versus male (aRR = 0.69; 95% CI, 0.60-0.79), Asian versus non-Hispanic White (aRR = 0.58; 95% CI, 0.39-0.87), and from the Midwest versus the Northeast (aRR = 0.76; 95% CI, 0.63-0.91) were less likely to report testing of a child. Children who had health insurance versus no health insurance (aRR = 1.38; 95% CI, 1.05-1.81), were attending in-person school/daycare versus not attending (aRR = 1.67; 95% CI, 1.43-1.95), and were from households with annual household income ≥$100 000 versus income <$50 000-$99 999 (aRR = 1.19; 95% CI, 1.02-1.40) were more likely to have tested for COVID-19. Half of parents (52.7%) reported the pediatrician's office as the most preferred testing venue, and 50.6% said they would allow their youngest child to be tested for COVID-19 at school/daycare if required. CONCLUSIONS: Greater efforts are needed to ensure access to COVID-19 testing for US children, including those without health insurance.

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).

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City.

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.

Bone outcomes in virally suppressed youth with HIV switching to tenofovir disoproxil fumarate.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is included in first-line antiretroviral treatment (ART) for adolescents living with HIV (ALWH). Associated toxicities remain a concern. OBJECTIVE: We evaluated bone and renal safety outcomes in virologically suppressed South African ALWH after switching to TDF. METHOD: We recruited virally suppressed (< 100 copies/mL) adolescents, aged 15-20 years, who switched from an abacavir (ABC)-based to a TDF-based efavirenz regimen. Bone mass and renal function were assessed at Week 0 and at Week 24 after the switch to TDF using dual-energy X-ray absorptiometry (DXA) and serum renal markers. A change in the lumbar spine (LS) and the whole-body less head (WBLH) bone mineral density (BMD) Z-scores and the estimated glomerular filtration rate (eGFR) between the two measures were compared (paired t-tests) and stratified by sex. RESULTS: Fifty participants (48% male), with a median duration of prior ART of 11.4 years, were enrolled. Among 47 participants with 24-week DXA results, 15 (32%) had either no change or a decreased LS-BMD after the switch, with a mean change of -1.6%. Overall, more female participants experienced this outcome: 58% versus 4%, P < 0.0001. The mean change (standard deviation) in the LS-Z-score was -0.03 (0.25) and in the WBLH-Z-score was 0.02 (0.24). A decrease in the eGFR from 132.2 to 120.4 was observed (P = 0.0003); however, the levels remained clinically acceptable. CONCLUSION: South African ALWH switching from abacavir to TDF-based ART experienced statistically significant decreases in eGFR but not in LS and WBLH BMD. Female ALWH were more likely to experience a decrease in LS-BMD and may require closer monitoring.

Parental plans to vaccinate children for COVID-19 in New York city.

Once COVID-19 vaccines are approved for children < 12 years of age, high pediatric vaccination coverage will be needed to help minimize the public health threat from the SARS-CoV-2 epidemic. We conducted an online survey of 1,119 parents and caregivers of children ≤ 12 years in New York City from March 9 to April 11, 2021. Among parents surveyed, 61.9% reported plans to vaccinate their youngest child for COVID-19, 14.8% said they do not plan to vaccinate their child and 23.3% were unsure. Female and non-Hispanic Black parents were least likely to report plans to vaccinate their children. Safety, effectiveness and perceptions that children do not need vaccination were the primary reasons for vaccine hesitancy/resistance. Parents who have or will vaccinate themselves were significantly more likely to report they would vaccinate their children. Efforts to increase awareness about vaccine safety and education about the importance of vaccinating children are needed.

Virologic Response to Very Early HIV Treatment in Neonates.

Factors that influence viral response when antiretroviral therapy (ART) is initiated in neonates are not well characterized. We assessed if there is consistency in predictive factors when operationalizing viral response using different methods. Data were collected from a clinical study in South Africa that started ART in neonates within 14 days of birth (2013-2018). Among 61 infants followed for ≥48 weeks after ART initiation, viral response through 72 weeks was defined by three methods: (1) clinical endpoints (virologic success, rebound, and failure); (2) time to viral suppression, i.e., any viral load (VL: copies/mL) <400, <50, or target not detected (TND) using time-to-event methods; and (3) latent class growth analysis (LCGA) to empirically estimate discrete groups with shared patterns of VL trajectories over time. We investigated the following factors: age at ART initiation, sex, birthweight, preterm birth, mode of delivery, breastfeeding, pre-treatment VL and CD4, maternal ART during pregnancy, and maternal VL and CD4 count. ART was initiated 0-48 h of birth among 57.4% of the infants, 48 h-7 days in 29.5% and 8-14 days in 13.1%. By Method 1, infants were categorized into 'success' (54.1%), 'rebound' (21.3%), and 'failure' (24.6%) for viral response. For Method 2, median time to achieving a VL <400, <50, or TND was 58, 123, and 331 days, respectively. For Method 3, infants were categorized into three trajectories: 'rapid decline' (29.5%), 'slow decline' (47.5%), and 'persistently high' (23.0%). All methods found that higher pre-treatment VL, particularly >100,000, was associated with less favorable viral outcomes. No exposure to maternal ART was associated with a better viral response, while a higher maternal VL was associated with less favorable viral response and higher maternal CD4 was associated with better viral response across all three methods. The LCGA method found that infants who initiated ART 8-14 days had less favorable viral response than those who initiated ART earlier. The other two methods trended in a similar direction. Across three methods to operationalize viral response in the context of early infant treatment, findings of factors associated with viral response were largely consistent, including infant pre-treatment VL, maternal VL, and maternal CD4 count.

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.

Persistently lower bone mass and bone turnover among South African children living with well controlled HIV.

OBJECTIVE: We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls. DESIGN: We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over 2 years. METHODS: Longitudinal analyses were conducted among 220 CLHIV and 220 controls. Anthropometric measurements, physical activity, antiretroviral regimen, virologic and immunologic status, whole body (WB) and lumbar spine (LS) bone mineral content (BMC) and bone mineral density (BMD) were collected (enrollment, 12 and 24 months). Bone turnover markers including C-telopeptide of type I collagen (CTx) and procollagen type I N-terminal propeptide (P1NP) and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble CD14 and high-sensitivity C-reactive protein (hsCRP) were collected at enrollment and 24 months. RESULTS: Compared with controls, CLHIV had significantly lower mean WB-BMC, WB-BMD, WB-BMC z scores, LS-BMC and LS-BMD as well as lower bone formation (P1NP) and resorption (CTx), and higher hsCRP and soluble CD14 over 24 months. CLHIV on efavirenz (EFV) had consistently lower TNF-alpha and IL-6 compared with those on ritonavir-boosted lopinavir (LPV/r) at all time points. CONCLUSION: Over 2 years of follow-up, South African CLHIV had persistently lower bone mass, bone turnover, and macrophage activation. Lower bone mass and higher pro-inflammatory cytokine profiles were consistently observed among those on LPV/r-based compared with EFV-based regimens.

Epigenetic Age in Young African American Adults With Perinatally Acquired HIV.

BACKGROUND: Prior studies have measured accelerated aging in people with HIV using a DNA methylation (DNAm)-based biomarker of aging, "epigenetic age," but data are limited in African American (AA) young adults with perinatally acquired HIV infection (PHIV). METHODS: We performed a cross-sectional study of AA young adults aged 20-35 years with PHIV (N = 31) and seronegative controls (N = 30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC array was used to measure DNAm age and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) EAA. RESULTS: PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r = 0.56, P < 0.01). PHIV had a higher mean EAA (2.86 ± 6.5 vs. -2.96 ± 3.9, P < 0.01) and EEAA (4.57 ± 13.0 vs. -4.72 ± 6.0, P < 0.01) than controls; however, IEAA was not different between groups. Among PHIV, EAA and EEAA were higher in those with HIV viral load ≥50 copies/mL than <50 copies/mL (EEA: 8.1 ± 5.2 vs. 0.11 ± 5.5, P = 0 < 0.01 and EEAA: 16.1 ± 10.6 vs. -1.83 ± 9.7, P < 0.01). We observed negative correlations (r = -0.36 to -0.31) between EEAA and executive function, attention, and language scores. CONCLUSIONS: In conclusion, EAA in blood was observed in AA young adults with PHIV on ART using 2 measures, including EEAA which upweights the contribution of immunosenescent cell types. However, there was no evidence of age acceleration with a measure independent of cell type composition.