Gestational weight gain in persons with HIV in the United States.

OBJECTIVE: We evaluated gestational weight gain (GWG) in pregnant persons with HIV (PWH) enrolled in the Surveillance Monitoring for ART Toxicities study. DESIGN: This was a cohort study. METHODS: GWG was classified as excessive, adequate, or inadequate; weekly GWG in second and third trimesters was calculated using National Academy of Medicine standards. Adjusted modified Poisson and linear regression models were fit with generalized estimating equations to assess the association of antiretroviral treatment (ART) with GWG outcomes stratified by timing of ART initiation [at conception (ART-C) and initiating during pregnancy (ART-I)]. RESULTS: We included 1477 pregnancies (847 ART-C, 630 ART-I) from 1282 PWH. The proportion of excessive, adequate, and inadequate GWG was 44, 24, and 32%, respectively. No associations of ART class with excessive GWG were observed overall. However, among ART-I pregnancies with overweight prepregnancy BMI-based, protease inhibitor-based, nonnucleoside reverse transcriptase inhibitor-based, and nucleoside reverse transcriptase inhibitor-based ART were associated with significantly lower GWG per week than integrase inhibitor (INSTI)-based ART [mean differences: -0.14, -0.27, and -0.29 kg/week, respectively]. Among ART-I pregnancies with obese prepregnancy BMI, lower weekly GWG was also observed for protease inhibitor-based vs. INSTI-based ART (mean difference: -0.14 kg/week). CONCLUSION: ART class type was not associated with excessive GWG. However, PWH entering pregnancy already overweight/obese and initiating INSTI-based ART had higher weekly GWG in second and third trimesters vs. other ART classes. Further studies to understand how increases in weekly GWG for overweight/obese PWH impinges on long-term maternal/child health are warranted.

Sexually Transmitted Infections in Pregnant People With Human Immunodeficiency Virus: Temporal Trends, Demographic Correlates, and Association With Preterm Birth.

BACKGROUND: We describe trends in prevalence and identify factors associated with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and Trichomonas vaginalis (TV) diagnosed in pregnancy among US people with human immunodeficiency virus (PWH) and evaluate associations of sexually transmitted infections (STIs) with preterm birth (PTB). METHODS: We included pregnant PWH enrolled in the Surveillance Monitoring for ART Toxicities dynamic cohort of the Pediatric HIV/AIDS Cohort Study network who delivered between 2010 and 2019. Multivariable log-binomial or Poisson generalized estimating equation models were used to estimate the association of calendar year with each STI, controlling for confounders; the association of demographic and clinical factors with each STI; and the association of each STI with PTB. RESULTS: The sample included 2241 pregnancies among 1821 PWH. Median age at delivery was 29.2 years; 71% of participants identified as Black or African American. STI prevalence was: CT 7.7%, NG 2.3%, syphilis 2.4%, and TV 14.5%; 30% had unknown TV status. There were no temporal changes in STI prevalence. Younger age and initial HIV viral load ≥400 copies/mL were associated with increased risk of CT, NG, and TV. Recreational substance use was a risk factor for NG, syphilis, and TV. No STI was associated with PTB. CONCLUSIONS: Unlike nationwide trends, no changes in STI prevalence during the study period were observed. The large proportion with unknown TV status underscores the need for increased adherence to screening guidelines. STIs diagnosed during pregnancy in PWH were not associated with risk of PTB.

Associations of FGF21 and GDF15 with mitochondrial dysfunction in children living with perinatally-acquired HIV: A cross-sectional evaluation of pediatric AIDS clinical trials group 219/219C.

BACKGROUND: In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults living with HIV. We assessed relationships of these biomarkers with MD in children living with perinatally-acquired HIV infection (CPHIV). SETTING: Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2-4 as "possible" MD. METHODS: Each case with MDC equaling 4 (MDC4; n = 23) was matched to one randomly selected control displaying no MDC (MDC0; n = 23) based on calendar date. Unmatched cases with MDC equaling 3 (MDC3; n = 71) were also assessed. Plasma samples proximal to diagnoses were assayed by ELISA. Mitokine distributions were compared using Wilcoxon tests, Spearman correlations were calculated, and associations with MD status were assessed by conditional logistic regression. RESULTS: Median FGF21 and GDF15 concentrations, respectively, were highest in MDC4 (143.9 and 1441.1 pg/mL), then MDC3 (104.0 and 726.5 pg/mL), and lowest in controls (89.4 and 484.7 pg/mL). Distributions of FGF21 (paired Wilcoxon rank sum p = 0.002) and GDF15 (paired Wilcoxon rank sum p<0.001) differed in MDC4 vs MDC0. Mitokine concentrations were correlated across all participants (r = 0.33; p<0.001). Unadjusted odds ratios of being MDC4 vs MDC0 were 5.2 [95% confidence interval (CI): 1.06-25.92] for FGF21 and 3.5 (95%CI: 1.19-10.25) for GDF15. Relationships persisted after covariate adjustments. CONCLUSION: FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.

Marijuana, Opioid, and Alcohol Use Among Pregnant and Postpartum Individuals Living With HIV in the US.

Importance: Amid the opioid epidemic and evolving legal and social changes with marijuana, little is known about substance use among pregnant and postpartum people living with HIV. Objectives: To evaluate trends in marijuana, alcohol, and opioid use during pregnancy and the first year postpartum among US people living with HIV and the differences in substance use based on marijuana legalization status. Design, Setting, and Participants: Data from the Surveillance Monitoring for Antiretroviral Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study were analyzed. SMARTT-enrolled, pregnant people living with HIV at 22 US sites from January 1, 2007, to July 1, 2019, with self-reported substance use data available in pregnancy, 1 year postpartum, or both were assessed. Exposures: Calendar year and state marijuana legalization status. Main Outcomes and Measures: The prevalence of any use of each of the following substances was calculated by calendar year, separately for pregnancy and postpartum: marijuana, alcohol, opioid, and concomitant alcohol and marijuana. Log binomial models were fit using general estimating equations to evaluate the mean annual change, accounting for repeat pregnancies. The study also evaluated differences in substance use by state recreational or medical marijuana legalization status. Results: Substance use data were available for 2926 pregnancies from 2310 people living with HIV (mean [SD] age, 28.8 [6.1] years; 822 [28.1%] Hispanic, 1859 [63.5%] non-Hispanic Black, 185 [6.3%] White, 24 [0.8%] of more than 1 race, 24 [0.8%] of other race or ethnicity [individuals who identified as American Indian, Asian, or Native Hawaiian or other Pacific Islander], and 12 [0.4%] with unknown or unreported race or ethnicity). Between 2007 and 2019, marijuana use during pregnancy increased from 7.1% to 11.7%, whereas alcohol and opioid use in pregnancy were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10.0%) use were common; marijuana use increased from 10.2% to 23.7% from 2007 to 2019, whereas postpartum alcohol use was unchanged. The adjusted mean risk of marijuana use increased by 7% (95% CI, 3%-10%) per year during pregnancy and 11% (95% CI, 7%-16%) per year postpartum. Postpartum concomitant alcohol and marijuana use increased by 10% (95% CI, 5%-15%) per year. Differences in substance use were not associated with recreational legalization, but increased marijuana use was associated with medical marijuana legalization. Conclusions and Relevance: In this cohort study, opioid use among pregnant people living with HIV remained stable, whereas marijuana use during pregnancy and postpartum increased over time and in states with legalized medical marijuana. These patterns of increasing marijuana use among pregnant and postpartum people living with HIV suggest that enhanced clinical attention is warranted, given the potential maternal and child health implications of substance use.

Racial/Ethnic Disparities in Longitudinal Emotional-Behavioral Functioning Among Youth Born to Women Living With HIV.

BACKGROUND: Youth with perinatal HIV exposure have demonstrated high rates of emotional-behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. SETTING: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). METHODS: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiver-reported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional-behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. RESULTS: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. CONCLUSIONS: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status.

Brief Report: Youth Living With Perinatally Acquired HIV Have Lower Physical Activity Levels as They Age Compared With HIV-Exposed Uninfected Youth.

BACKGROUND: Few studies have evaluated physical activity patterns or their association with vascular inflammation among youth living with perinatally acquired HIV (YPHIV). METHODS: We assessed YPHIV and youth perinatally HIV-exposed but uninfected (YPHEU) in the PHACS Adolescent Master Protocol with at least one Block physical activity questionnaire (PAQ) completed between ages 7-19 years. Physical activity metrics were as follows: (1) daily total energy expenditure (TEE) and (2) physical activity duration (PAD) defined as the minutes of daily moderate and vigorous activities. In a subgroup, we measured serum biomarkers of coagulation (fibrinogen and P-selectin) and endothelial dysfunction (soluble intracellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, and E-selectin) obtained within 3 months of a single PAQ. Repeated measures linear regression models were used to compare the trajectories of log-transformed TEE and PAD by HIV status, adjusting for confounders. Spearman correlations were calculated to assess the relationship of TEE and PAD with vascular biomarkers. RESULTS: Five hundred ninety-six youth (387 YPHIV and 209 YPHEU) completed 1552 PAQs (median PAQs completed = 3). The median age at enrollment (Q1, Q3) was 11 (9, 13) years. TEE and PAD increased with age in both YPHIV and YPHEU. However, even after adjusting for confounders, YPHIV had significantly less increase per year than YPHEU for TEE (5.7% [95% confidence interval (CI): -9.9% to -1.4%, P = 0.010] less) and PAD (5.2% [95% CI: -9.2% to -1.1%, P = 0.016] less). Among 302 youth with biomarker measures (187 YPHIV and 114 YPHEU), we observed little correlation with TEE or PAD. CONCLUSIONS: Both groups had increases in physical activity levels as they aged, but YPHIV had smaller increases throughout adolescence compared with YPHEU, which may impact long-term health.

Health Care-Associated Infections Among Critically Ill Children in the US, 2013-2018.

Importance: Central catheter-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) increase morbidity, mortality, and health care costs in pediatric patients. Objective: To examine changes over time in CLABSI and CAUTI rates between 2013 and 2018 in neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs) using prospective surveillance data from community hospitals, children's hospitals, and pediatric units within general hospitals. Design, Setting, and Participants: This time series study included 176 US hospitals reporting pediatric health care-associated infection surveillance data to the National Healthcare Safety Network from January 1, 2013, to June 30, 2018. Patients aged 18 years or younger admitted to PICUs or level III NICUs were included in the analysis. Main Outcomes and Measures: The primary outcomes were device-associated rates of CLABSI in NICUs and PICUs and CAUTI in PICUs (infections per 1000 device-days). Secondary outcomes included population-based rates (infections per 10 000 patient-days) and device utilization (device-days per patient-days). Regression models were fit using generalized estimating equations to assess yearly changes in CLABSI and CAUTI rates, adjusted for birth weight (≤1500 vs >1500 g) in neonatal models. Results: Of the 176 hospitals, 132 hospitals with NICUs and 114 hospitals with PICUs contributed data. Of these, NICUs reported 6 064 172 patient-days and 1 363 700 central line-days and PICUs reported 1 999 979 patient-days, 925 956 central catheter-days, and 327 599 indwelling urinary catheter-days. In NICUs, there were no significant changes in yearly trends in device-associated (incidence rate ratio [IRR] per year, 0.99; 95% CI, 0.95-1.03) and population-based (IRR, 0.96; 95% CI, 0.92-1.00) CLABSI rates or central catheter utilization (odds ratio [OR], 0.97; 95% CI, 0.95-1.00). Results were similar in PICUs, with device-associated (IRR, 1.03; 95% CI, 0.99-1.07) and population-based (IRR, 1.03; 95% CI, 0.99-1.07) CLABSI rates and central catheter utilization (OR, 0.99; 95% CI, 0.97-1.01) remaining stable. While device-associated CAUTI rates in PICUs also remained unchanged over time (IRR, 0.97; 95% CI, 0.91-1.03), population-based CAUTI rates significantly decreased by 8% per year (IRR, 0.92; 95% CI, 0.86-0.98) and indwelling urinary catheter utilization significantly decreased by 6% per year (OR, 0.94; 95% CI, 0.91-0.96). Conclusions and Relevance: Recent trends in CLABSI rates noted in this study among critically ill neonates and children in a large cohort of US hospitals indicate that past gains have held, without evidence of further improvements, suggesting novel approaches for CLABSI prevention are needed. Modest improvements in population-based CAUTI rates likely reflect more judicious use of urinary catheters.

Association Between Federal Value-Based Incentive Programs and Health Care-Associated Infection Rates in Safety-Net and Non-Safety-Net Hospitals.

Importance: In the US, federal value-based incentive programs are more likely to penalize safety-net institutions than non-safety-net institutions. Whether these programs differentially change the rates of targeted health care-associated infections in safety-net vs non-safety-net hospitals is unknown. Objective: To assess the association of Hospital-Acquired Condition Reduction Program (HACRP) and Hospital Value-Based Purchasing (HVBP) implementation with changes in rates of targeted health care-associated infections and disparities in rates among safety-net and non-safety-net hospitals. Design, Setting, and Participants: This interrupted time series included all US acute care hospitals enrolled in the Preventing Avoidable Infectious Complications by Adjusting Payment study that participated in mandatory reporting to the National Healthcare Safety Network from January 1, 2013, through June 30, 2018. Hospital characteristics were obtained from the 2015 American Hospital Association annual survey. Penalty statuses for 2015 to 2018 were obtained from Hospital Compare. Data were analyzed between July 9, 2018, and October 1, 2019. Exposures: HACRP and HVBP implementation in fiscal year 2015 or 2016. Main Outcomes and Measures: The primary outcomes were rates of 4 health care-associated infections: central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI) after colon surgical procedures, and SSI after abdominal hysterectomy procedures. Regression models were fit using generalized estimating equations to assess the association of HACRP and HVBP implementation with health care-associated infection rates and disparities in infection rates. Results: Of the 618 acute care hospitals included in this study, 473 (76.5%) were non-safety net and 145 (23.5%) were considered safety net. In these hospitals, HACRP and HVBP implementation was not associated with improvements in level or trend for any health care-associated infection examined (eg, CAUTI in safety-net hospitals: incidence rate ratio [IRR] for level change, 0.98 [95% CI, 0.79-1.23; P = .89]; IRR for change in slope, 1.00 [95% CI, 0.97-1.03; P = .80]). Before program implementation, infection rates were statistically significantly higher for safety-net than for non-safety-net hospitals for CLABSI (IRR, 1.23; 95% CI, 1.07-1.42; P = .004), CAUTI (IRR, 1.38; 95% CI, 1.16-1.64; P < .001), and SSI after colon surgical procedure (odds ratio [OR], 1.26; 95% CI, 1.06-1.50; P = .009). The disparity persisted over time when comparing the last year of the study with the first year (CLABSI: ratio of ratios [ROR], 0.93 [95% CI, 0.77-1.13; P = .48]; CAUTI: ROR, 0.90 [95% CI, 0.73-1.10; P = .31]; SSI after colon surgical procedures: ROR, 0.96 [95% CI, 0.78-1.20; P = .75]). Rates of SSI after abdominal hysterectomy procedure were similar in safety-net and non-safety-net hospitals before implementation (OR, 1.13; 95% CI, 0.91-1.40; P = .27) but higher after implementation (OR, 1.43; 95% CI, 1.11-1.83; P = .006), although this change was not significant (ROR, 1.20; 95% CI, 0.91-1.59; P = .20). Conclusions and Relevance: This study found that HACRP and HVBP implementation was not associated with any improvements in targeted health care-associated infections among safety-net or non-safety-net hospitals or with changes in disparities in infection rates. Given the persistent health care-associated infection rate disparities, these programs appear to function as a disproportionate penalty system for safety-net hospitals that offer no measurable benefits for patients.

Longitudinal effects of Nucleos(t)ide analogue therapy in chronic hepatitis B patients and the utility of non-invasive fibrosis markers during treatment: A single-center experience for up to 17 years.

BACKGROUND: Fibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated. AIMS: To characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients. METHODS: Histology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naïve CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally. RESULTS: 80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >0.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4-6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03). CONCLUSION: Early dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment.

Comparison of hospital surgical site infection rates and rankings using claims versus National Healthcare Safety Network surveillance data.

National policies target healthcare-associated infections using medical claims and National Healthcare Safety Network surveillance data. We found low concordance between the 2 data sources in rates and rankings for surgical site infection following colon surgery in 155 hospitals, underscoring the limitations in evaluating hospital quality by claims data.

Impact of the 2012 Medicaid Health Care-Acquired Conditions Policy on Catheter-Associated Urinary Tract Infection and Vascular Catheter-Associated Infection Billing Rates.

In July 2012, the Centers for Medicare & Medicaid Services ceased hospital Medicaid reimbursements for certain health care-acquired conditions. Using billing data from 2008-2014, we found no impact of this policy on rates of 2 targeted conditions, vascular catheter-associated infections and catheter-associated urinary tract infections, among Medicaid or non-Medicaid patients.