Blood Lead Levels of Children in Flint, Michigan: 2006-2016.

OBJECTIVE: We evaluated the increases in blood lead levels (BLLs) observed in young children in Flint, Michigan, during their exposure to corrosive Flint River water during the years 2014 and 2015 and compared their BLLs to those of Flint children measured during the years 2006-2013 and 2016. STUDY DESIGN: This was a retrospective study design using BLLs extracted from databases from 2006 to 2016. We analyzed a population sample of 15 817 BLLs from children aged ≤5 years with potential exposure to contaminated Flint River water. Percentages of BLLs ≥5.0 µg/dL and geometric mean (GM) BLLs were analyzed over time. RESULTS: A significant decline in the percentages of BLLs ≥5.0 µg/dL from 11.8% in 2006 to 3.2% in 2016 was observed (P < .001). GM ± SE BLLs decreased from 2.33 ± 0.04 µg/dL in 2006 to 1.15 ± 0.02 µg/dL in 2016 (P < .001). GM BLLs increased twice: from 1.75 ± 0.03 µg/dL to 1.87 ± 0.03 µg/dL (2010-2011) and from 1.19 ± 0.02 µg/dL to 1.30 ± 0.02 µg/dL (2014-2015). Overall, from 2006 to 2016, there was a 72.9% decrease in the percentage of children with BLLs ≥5.0 µg/dL and a 50.6% decrease in GM BLLs. CONCLUSION: These findings suggest that the 11 year trend of annual decreases in BLLs in children in Flint, Michigan, reversed to a degree consistent with random variation from 2010 to 2011, and again during the exposure to Flint River water in 2014-2015. Historically, public health efforts to reduce BLLs of young children in Flint have been effective over the 11-year period studied.

Blood Lead Concentrations of Children in the United States: A Comparison of States Using Two Very Large Databases.

OBJECTIVES: To determine whether there are substantial differences by state between 2 large datasets in the proportion of children with elevated blood lead levels (BLLs); to identify states in which the percentage of elevated BLLs is high in either or both datasets; and to compare the percentage of elevated BLLs in individual states with those of children living in Flint, Michigan, during the months when these children were exposed to lead-contaminated drinking water. STUDY DESIGN: Tables of BLLs for individual states from the Quest Diagnostics and the Centers for Disease Control and Prevention datasets for 2014-2015, containing more than 3 million BLLs of young children?

Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy.

BACKGROUND: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. METHODS: We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. RESULTS: Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. CONCLUSIONS: Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.

Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.

BACKGROUND: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. METHODS: Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were >95 % for both the at-risk cohort and those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

Chronic kidney disease associated with perinatal HIV infection in children and adolescents.

BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Resident Perspectives on Palliative Care at an Urban Teaching Hospital.

Background: There has been an increasing need to address end of life (EOL) care and palliative care in an era when measures to extend life for terminal illnesses are often initiated without consideration of quality of life. Addressing the barriers for resident physicians to initiate EOL conversations with patients is an important step towards eliminating the disconnect between patient wishes and provider goals. Objective: To assess resident physician perspectives on initiating palliative care conversations with terminally ill patients at an urban teaching hospital. Methods: This paper solicited the experiences of pediatric, general surgery, and internal medicine residents through an anonymous survey to assess exposure to palliative care during training, comfort with providing palliative care, and barriers to implementing effective palliative care. Results: 45% of residents reported exposure to palliative care prior to medical training. Ninety-three percent of these residents reported being formally introduced to palliative care during medical training through formal lecture, although the majority reported also being exposed through either small group discussions or informal teaching sessions. Time constraints and lack of knowledge on how to initiate and continue conversations surrounding EOL care were the greatest barriers to effectively caring for patients with terminal illnesses. Residents concurred that either attending physicians or hospital-designated palliative care providers should initiate palliative care discussions, with care managed by an interdisciplinary palliative care team; this consensus demonstrates a potential assumption that another provider will initiate EOL discussions. Conclusions: This study evaluated the current state of physician training in EOL care and provided support for the use of experience-based training as an important adjunct to traditional didactic lectures in physician education.

Possible mitochondrial dysfunction and its association with antiretroviral therapy use in children perinatally infected with HIV.

BACKGROUND: Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection. METHODS: Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression. RESULTS: Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction. CONCLUSIONS: Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.

Blood Lead Concentrations in Newark Children. Comment on Franklin, R.C.; Behmer Hansen, R.A.; Pierce, J.M.; Tsitouras, D.J.; Mazzola, C.A. Broken Promises to the People of Newark: A Historical Review of the Newark Uprising, the Newark Agreements, and Rutgers New Jersey Medical School's Commitments to Newark. Int. J. Environ. Res. Public Health 2021, 18, 2117.

The recently published article of RC Franklin et al [...].

The Impact and Perception of Cell Phone Usage in a Teaching Hospital Setting.

OBJECTIVE: To evaluate perceptions regarding cell phone use in a teaching hospital setting among health care providers, residents, medical students, and patients. METHODS: Fifty-three medical students, 41 resident physicians, 32 attending physicians, and 46 nurses working at University Hospital completed a questionnaire about cell phone use practices and their perceptions of cell phone use in the hospital. Forty-three inpatients admitted to medical/surgical units at University Hospital were surveyed at bedside about their perceptions regarding physicians' cell phone use. RESULTS: All health care providers identified cell phones as a risk to patient confidentiality with no specific group significantly more likely to attribute risk than another. Practitioners were identified as either primarily as inpatient or outpatient practitioners. Inpatient practitioners were significantly more likely to rate cell phones as beneficial to patient care than outpatient practitioners. Physicians were statistically more likely to rate mobile phones as beneficial to patient care as compared to nurses. Among the patient population surveyed, one quarter noted that their physician had used a cell phone in their presence. The majority of those patients observing practitioner cell phone use had reported a beneficial or neutral impact on their care. Significance: Perceived risk of cell phones to patient confidentiality was equal across health care providers surveyed. Physician and medical students were significantly more likely to rate cell phones as beneficial to patients' care than nurse providers. Patients indicated that their physicians used cell phones in their presence at low rates and reported that the use was either neutral or beneficial to the care they received.

Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003-2008 has been incorporated into this document.

Randomized controlled trial of feeding a concentrated formula to infants born to women infected by human immunodeficiency virus.

OBJECTIVE: We tested the hypothesis that concentrated formula (CF) begun within the first 2 weeks of life increases growth in infants born to human immunodeficiency virus (HIV)-infected mothers. MATERIALS AND METHODS: HIV-exposed infants from the United States, the Bahamas, and Brazil were randomized in a double-blind, controlled trial to receive either a CF (87 kcal/100 mL [26 kcal/oz]) or a standard formula (SF; 67 kcal/100 mL [20 kcal/oz]) for 8 weeks. This article presents results for infants who were not determined to be HIV infected based on testing at 4 weeks. Primary outcomes were safety, tolerability, and growth in weight and length. RESULTS: Two thousand ninety-seven infants were enrolled, of whom 1998 were uninfected and had study formula dispensed. At weeks 4 and 8, uninfected infants receiving CF showed higher energy intake than those who were receiving SF (P < 0.001). By week 8, uninfected infants assigned to CF weighed more than infants receiving SF. There were no consistent differences in measures of tolerability, and rates of discontinuation or perceived formula intolerance were similar between treatment groups. CONCLUSIONS: A CF is well tolerated and results in increased weight gain compared with SF. Until the HIV status of an infant is reliably determined, early introduction of a CF in HIV-exposed children may have beneficial effects on growth. The role of early nutritional intervention remains to be determined for individuals living in countries with endemic malnutrition for whom formula feeding is a viable option.

Essential trace elements and progression and management of HIV infection.

This review was written to update the review that we published in Nutrition Research in 2007 by examining studies published in the last 11 years which describe the effects of trace mineral deficiencies and micronutrient supplementation on HIV infection and its progression. In addition, we included studies that explore the interactions between Highly Active Anti-Retroviral Therapy (HAART) and micronutrient nutrition, focusing on the essential trace minerals. This review summarizes the results described in relevant articles that were identified by literature searches conducted using the OVID Medline database. Four of the nine essential trace minerals, specifically chromium, iron, selenium, and zinc, can influence HIV progression and/or its treatment. Notably, copper-containing filters may prevent transmission of the HIV virus via breastfeeding. However, there is a lack of good evidence to date that fluoride, iodine, manganese, or molybdenum influence HIV infection. Recent studies reveal that HAART can alter serum trace mineral and vitamin concentrations, but the effects vary based on the medications used. Although they have contributed useful new data, the sample sizes for most of these studies were too small to draw definitive conclusions for introducing changes in the management of HIV infection. Larger studies are needed to better understand and define the roles of trace mineral and vitamin deficiencies and micronutrient supplementation in the management and treatment of HIV-infected patients.

Blood Lead Levels in Females of Childbearing Age in Flint, Michigan, and the Water Crisis.

OBJECTIVE: To compare blood lead levels in females of childbearing age, 12-50 years, living within and adjacent to Flint, Michigan, before, during, and after the Flint River water exposure and compare the levels to those that have been shown to cause fetal loss and preterm birth. METHODS: The switch in the community water source to the Flint River occurred on April 25, 2014, and was reverted to the original source on October 15, 2015. Using a retrospective cross-sectional study design using geocoded blood lead levels obtained from all females of childbearing age available from a single hospital database, we compared blood lead levels for the following 18-month time periods: April 25, 2012-October 15, 2013 (PRE), April 25, 2014-October 15, 2015 (DURING), and April 25, 2016-October 15, 2017 (POST). RESULTS: Results are reported as geometric mean (95% CI). Within Flint, PRE blood lead levels in females of childbearing age were 0.69 micrograms/dL (95% CI 0.63-0.75), DURING blood lead levels were 0.65 micrograms/dL (95% CI 0.60-0.71), and POST blood lead levels were 0.55 micrograms/dL (95% CI 0.54-0.56). DURING Flint River water exposure blood lead levels were not significantly different than the PRE Flint River water time period. POST Flint River water exposure blood lead levels were significantly lower than both PRE and DURING levels. Overall, lower blood lead levels were found outside the Flint boundary in all cohorts. CONCLUSION: Blood lead levels in Flint females of childbearing age did not increase during the Flint River water exposure and subsequent 18-month time period. Mean blood lead levels during the Flint River water exposure are not consistent with the markedly higher blood lead levels reported in the literature to be associated with fetal loss, low birth weight, or preterm birth.

Analysis of blood lead levels of young children in Flint, Michigan before and during the 18-month switch to Flint River water.

Background: The toxicity of lead, like any xenobiotic, is directly linked to the duration of exposure and toxin concentration in the body. The elevation in blood lead levels (BLLs) in young Flint, Michigan children noted in time-periods before, and during the 18-month exposure to Flint River water (FRW) from 25 April 2014 to 15 October 2015 is well-known internationally. The length of time BLLs were elevated is unknown, yet key in understanding the potential health impact of the event. The objective of this study was to evaluate whether BLLs in Flint children were increased during the entire 18-month FRW exposure compared to similar earlier time periods. Methods: We conducted a retrospective study analyzing BLLs from Flint children aged 5 years and under. The geometric mean (GM) BLLs and percentages of BLLs ≥5.0 µg/dL in Period I: 25 April 2006 to 15 October 2007 (earliest timeframe available for study) and Period II: 25 April 2012 to 15 October 2013 (timeframe immediately before the water switch), were compared to Period III, 25 April 2014 to 15 October 2015 (FRW exposure). Results: There were 5663 BLLs available for study. GM ± SE BLLs decreased from 2.19 ± 0.03 µg/dL in Period I to 1.47 ± 0.02 µg/dL in Period II [95% CI, 0.64, 0.79]; p<.001 and decreased further to 1.32 ± 0.02 µg/dL during the FRW Period III [95% CI, 0.79, 0.95]; p<.001. The percentage of BLLs ≥5.0 µg/dL decreased from Period I (10.6%) to Period II (3.3%) [95% CI, 5.7, 8.8]; p<.001 and from Period I to Period III (3.9%) [95% CI, 5.0, 8.2]; p=.002. The 0.6% increase from Period II to Period III was not statistically significant [95% CI, -1.9, 0.57]; p=.30. Conclusion: Analyses of GM and percentages ≥5.0 µg/dL of BLLs do not support the occurrence of a global increase in BLLs in young children of Flint during the entire 18-month period of FRW exposure.

Do-not-resuscitate orders and/or hospice care, psychological health, and quality of life among children/adolescents with acquired immune deficiency syndrome.

OBJECTIVE: The frequency of do-not-resuscitate (DNR) orders and hospice enrollment in children/adolescents living with acquired immune deficiency syndrome (AIDS) and followed in Pediatric AIDS Clinical Trials Group (PACTG) Study 219C was examined, and evaluated for any association with racial disparities or enhanced quality of life (QOL), particularly psychological adjustment. METHODS: A cross-sectional analysis of children with AIDS enrolled in this prospective multicenter observational study between 2000 and 2005 was conducted to evaluate the incidence of DNR/hospice overall and by calendar time. Linear regression models were used to compare caregivers' reported QOL scores within 6 domains between those with and without DNR/hospice care, adjusting for confounders. RESULTS: Seven hundred twenty-six (726) children with AIDS had a mean age of 12.9 years (standard deviation [SD]=4.5), 51% were male, 60% black, 25% Hispanic. Twenty-one (2.9%) had either a DNR order (n=16), hospice enrollment (n=7), or both (n=2). Of 41 children who died, 80% had no DNR/hospice care. Increased odds of DNR/hospice were observed for those with CD4% less than 15%, no current antiretroviral use, and prior hospitalization. No differences by race were detected. Adjusted mean QOL scores were significantly lower for those with DNR/hospice enrollment than those without across all domains except for psychological status and health care utilization. Poorer psychological status correlated with higher symptom distress, but not with DNR/hospice enrollment after adjusting for symptoms. CONCLUSIONS: Children who died of AIDS rarely had DNR/hospice enrollment. National guidelines recommend that quality palliative care be integrated routinely with HIV care. Further research is needed to explore the barriers to palliative care and advance care planning in this population.

Negative life events: risk to health-related quality of life in children and youth with HIV infection.

Children and youth with perinatally acquired HIV infection are living longer because of improved drug therapies, but they may be at risk for poor health-related quality of life (HRQOL) outcomes because of nondisease factors. Families affected by HIV disease are more likely to experience major negative life events (NLEs). The effects of NLEs, shown to impact HRQOL in children with other chronic illnesses, have not been evaluated in children with HIV infection. The primary objective of this study was to determine if NLEs occurring in the previous 12 months were associated with increased risk for poorer outcomes in three measures of HRQOL (health perception, behavior problems, and symptom distress) in a cohort of children and youth with HIV infection. The authors conducted a cross-sectional analysis of data determined in 1999 from 1,018 children and youth 5 to 21 years of age enrolled in a longitudinal follow-up study. Multivariate logistic regressions estimated the odds for worse HRQOL outcomes. Children and youth with one or more NLEs had significantly lower health perceptions, more behavior problems, and greater symptom distress than children with no reported NLEs. The occurrence of NLEs may present a significant nondisease risk for diminished HRQOL among children and youth challenged by HIV disease. Nursing efforts to support these younger patients and their families sustaining major family disruption caused by NLEs may improve overall health outcomes in this vulnerable population.

Sexually Transmitted Infections in Youth With Controlled and Uncontrolled Human Immunodeficiency Virus Infection.

BACKGROUND: Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), disproportionately affect adolescents and young adults (AYAs) ages 13-24 years. Sexually transmitted infections likewise are a risk factor for HIV acquisition and transmission; however, there is a lack of data on STI acquisition in HIV-infected AYAs. METHODS: We determined the incidence of STIs in HIV-infected AYAs 12.5 <25 years of age in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 observational cohort study. Univariate and multivariable logistic regression models were used to evaluate the association of HIV control (mean viral load <500 copies/mL and CD4+ T cells >500 cells/mm3 in the year preceding STI diagnosis) and other risk factors with STI occurrence. RESULTS: Of 1201 enrolled subjects, 1042 participants met age criteria and were included (49% male, 61% black, 88% perinatally infected; mean age 18.3 years). One hundred twenty participants had at least 1 STI on study, of whom 93 had their first lifetime STI (incidence rate = 2.8/100 person-years). For individual STI categories, 155 incident category-specific events were reported; human papillomavirus (HPV) and chlamydial infections were the most common. In the multivariable model, having an STI was associated with older age (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 1.05-1.22), female sex (aOR = 2.65; 95% CI, 1.67-4.21), nonperinatal HIV acquisition (aOR = 2.33; 95% CI, 1.29-4.22), and uncontrolled HIV infection (aOR = 2.05; 95% CI, 1.29-3.25). CONCLUSIONS: Sexually transmitted infection acquisition in HIV-infected AYAs is associated with older age, female sex, nonperinatal HIV acquisition, and poorly controlled HIV infection. Substantial rates of STIs among HIV-infected AYAs support enhanced preventive interventions, including safe-sex practices and HPV vaccination, and antiretroviral adherence strategies.

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status. Design, Setting, and Participants: Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and ≥500/µL), and a combined measure of VL and ARV status (VL <400 or ≥400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017. Main Outcomes and Measures: Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories. Results: A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/µL compared with 7- to 12-year-old participants (30% and 44% vs 22% of person-time with a VL≥400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count <200/µL; P < .001 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 cell counts, as expected. The mortality rate among older PHIVY was 6 to 12 times that among the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 cell counts after adjusting for age. Conclusions and Relevance: Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ARV therapy adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY.

Toxicities of antiretroviral therapy in children.

The addition of highly active antiretroviral therapy to the complex regimens used to treat HIV-infected persons has extended the lives of millions. Despite the proven benefits of antiretroviral therapy, adverse events can occur with its use. These reactions can be separated into several distinct categories: mitochondrial dysfunction, metabolic abnormalities, hematologic complications, and allergic reactions. Drug-associated complications can be particularly challenging to treat when they occur in pediatric HIV patients. Care providers who manage HIV-infected children have to be cognizant of these complications when patients present with symptoms because some can mimic manifestations of HIV infection itself. These adverse reactions are neither uncommon nor unexpected, and discontinuation of the inciting agent is not always mandated. But every effort must be made to address them when they do occur so that adequate treatment is given in a timely manner.