RESUMO
Human immunodeficiency virus (HIV) viral load (VL) is an important quantitative marker of disease progression and treatment response in people living with HIV infection, including children with perinatally acquired HIV. Measures of VL are often used to predict different outcomes of interest in this population, such as HIV-associated neurocognitive disorder. One popular approach to summarizing historical viral burden is the area under a time-VL curve (AUC). However, alternative historical VL summaries (HVS) may better answer the research question of interest. In this article, we discuss and contrast the AUC with alternative HVS, including the time-averaged AUC, duration of viremia, percentage of time with suppressed VL, peak VL, and age at peak VL. Using data on youth with perinatally acquired HIV infection from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, we show that HVS and their associations with full-scale intelligence quotient depend on when the VLs were measured. When VL measurements are incomplete, as can be the case in observational studies, analysis results may be subject to selection bias. To alleviate bias, we detail an imputation strategy, and we present a simulation study demonstrating that unbiased estimation of a historical VL summary is possible with a correctly specified imputation model.
Assuntos
Infecções por HIV , Adolescente , Criança , Estudos de Coortes , Humanos , Testes Sorológicos , Carga Viral , ViremiaRESUMO
BACKGROUND: We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. METHODS: Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)â <â 70 and 247 CSAâ ≥â 70 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes. RESULTS: Twenty-nine SNVs in 24 genes reaching Pâ ≤â .002 and OR ≥ 1.5 comparing CSAâ <â 70 to CSA ≥ 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (Pâ <â .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (Pâ <â .0001 and Pâ <â .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1ß following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1ß release. CONCLUSIONS: Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.
Assuntos
Infecções por HIV/complicações , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Inflamação/genética , Transtornos Neurocognitivos/genética , Proteínas 14-3-3 , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Genômica , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Humanos , Lactente , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana , Microglia , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/virologia , Receptores CCRRESUMO
BACKGROUND: Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization. METHODS: HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. RESULTS: A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. CONCLUSIONS: Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.
Assuntos
Infecções por HIV , Criança , Estudos de Coortes , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Incidência , Lactente , Gravidez , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. OBJECTIVE: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. METHODS: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. RESULTS: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. CONCLUSION: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.
Assuntos
Infecções por HIV/complicações , Doenças Periodontais/metabolismo , Saliva/metabolismo , Adolescente , Bactérias , Criança , Cromatografia Líquida , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Metabolômica , Saúde Bucal , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
BACKGROUND: Increased incidence and prevalence of asthma have been documented for perinatally HIV-infected youth 10 to 21 years of age compared with HIV-exposed uninfected (HEU) youth. OBJECTIVE: We sought to perform objective pulmonary function tests (PFTs) in HIV-infected and HEU youth with and without diagnosed asthma. METHOD: Asthma was determined in 370 participants (218 HIV-infected and 152 HEU participants) by means of chart review and self-report at 13 sites. Interpretable PFTs (188 HIV-infected and 132 HEU participants) were classified as obstructive, restrictive, or normal, and reversibility was determined after bronchodilator inhalation. Values for HIV-1 RNA, CD4 and CD8 T cells, eosinophils, total IgE, allergen-specific IgE, and urinary cotinine were measured. Adjusted prevalence ratios (PRs) of asthma and PFT outcomes were determined for HIV-infected participants relative to HEU participants, controlling for age, race/ethnicity, and sex. RESULTS: Current asthma was identified in 75 (34%) of 218 HIV-infected participants and 38 (25%) of 152 HEU participants (adjusted PR, 1.33; P = .11). The prevalence of obstructive disease did not differ by HIV status. Reversibility was less likely in HIV-infected youth than in HEU youth (17/183 [9%] vs 21/126 [17%]; adjusted PR, 0.47; P = .020) overall and among just those with obstructive PFT results (adjusted PR, 0.46; P = .016). Among HIV-infected youth with current asthma, serum IgE levels were inversely correlated with CD8 T-cell counts and positively correlated with eosinophil counts and not associated with CD4 T-cell counts. HIV-infected youth had lower association of specific IgE levels to several inhalant and food allergens compared with HEU participants and significantly lower CD4/CD8 T-cell ratios (suggesting immune imbalance). CONCLUSION: Compared with HEU youth, HIV-infected youth demonstrated decreased reversibility of obstructive lung disease, which is atypical of asthma. This might indicate an early stage of chronic obstructive pulmonary disease. Follow-up into adulthood is warranted to further define their pulmonary outcomes.
Assuntos
Asma/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Eosinófilos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adolescente , Asma/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Imunoglobulina E/metabolismo , Incidência , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Prevalência , Testes de Função Respiratória , Fatores de Tempo , Estados Unidos , Carga ViralRESUMO
BACKGROUND.: Early antiretroviral therapy (ART) limits proviral reservoirs, a goal for human immunodeficiency virus type 1 (HIV-1) remission strategies. Whether this is an immediate or long-term effect of virologic suppression (VS) in perinatal infection is unknown. METHODS.: We quantified HIV-1 DNA longitudinally for up to 14 years in peripheral blood mononuclear cells (PBMCs) among 61 perinatally HIV-1-infected youths in the Pediatric HIV/AIDS Cohort Study who achieved VS at different ages. Participants in group 1 (n = 13) were <1 year of age and in group 2 (n = 48) from 1 through 5 years of age at VS. Piecewise linear mixed-effects regression models assessed the effect of age at VS on HIV-1 DNA trajectories during VS. RESULTS.: In the first 2 years following VS, HIV-1 DNA levels decreased by -0.25 (95% confidence interval [CI], -.36 to -.13) log10 copies/million PBMCs per year and was faster with early VS by age 1 year compared with after age 1 (-0.50 and -0.15 log10 copies/million PBMCs per year, respectively). Between years 2 and 14 from VS, HIV-1 DNA decayed by -0.05 (95% CI, -.06 to -.03) log10 copies/million PBMCs per year and was no longer significantly different between groups. The estimated mean half-life of HIV-1 DNA from VS was 15.9 years and was shorter for group 1 compared to group 2 at 5.9 years and 18.8 years, respectively (P = .09). Adjusting for CD4 cell counts had no effect on decay estimates. CONCLUSIONS.: Early effective, long-term ART initiated from infancy leads to decay of HIV-1-infected cells to exceedingly low concentrations desired for HIV-1 remission strategies.
Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Viral/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Adolescente , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Pré-Escolar , Estudos de Coortes , DNA Viral/sangue , Feminino , Seguimentos , Infecções por HIV/prevenção & controle , HIV-1/genética , Humanos , Lactente , Recém-Nascido , Leucócitos Mononucleares/efeitos dos fármacos , Modelos Lineares , Estudos Longitudinais , Masculino , Provírus/genética , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: Pregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined. METHODS: We compared preterm delivery and birth weight (BW) outcomes (low BW [LBW], <2500 g), small-for-gestational-age [SGA], and BW z scores [BWZ]) in HIV-exposed uninfected infants of PHIV vs nonperinatally HIV-infected (NPHIV) pregnant women in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities or International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 studies. Mixed effects models and log binomial models were used to assess the association of maternal PHIV status with infant outcomes. Age-stratified analyses were performed. RESULTS: From 1998 to 2013, 2270 HIV-infected pregnant women delivered 2692 newborns (270 born to PHIV and 2422 to NPHIV women). PHIV women were younger, (mean age 21 vs 25 years, P < .01) and more likely to have a pregnancy CD4 count <200 cells/mm3 (19% vs 11%, P = .01). No associations between maternal PHIV status and preterm delivery, SGA, or LBW were observed. After adjustment, BWZ was 0.12 lower in infants of PHIV vs NPHIV women (adjusted mean, -0.45 vs -0.33; P = .04). Among women aged 23-30 years (n = 1770), maternal PHIV was associated with LBW (aRR = 1.74; 95% confidence interval, 1.18, 2.58; P < .01). CONCLUSION: The overall lack of association between maternal PHIV status and preterm delivery or infant BW outcomes is reassuring. The higher rates of LBW observed in PHIV women aged 23-30 years warrants further mechanism-based investigations as this is a rapidly growing and aging population worldwide. CLINICAL TRIALS REGISTRATION: PHACS SMARTT study, NCT01310023. CLINICAL TRIALS REGISTRATION: IMPAACT 1025, NCT00028145.
Assuntos
Peso ao Nascer , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/sangue , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Gravidez , Estudos Prospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1years). PHIV youth had smaller (2.8-5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0-13.4%; marijuana use: 10.1-16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.
Assuntos
Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Substância Cinzenta/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Adolescente , Encéfalo/patologia , Criança , Feminino , Substância Cinzenta/patologia , Infecções por HIV/complicações , Infecções por HIV/patologia , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tamanho do Órgão/fisiologia , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/patologia , Adulto JovemRESUMO
BACKGROUND: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status. METHODS: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics. RESULTS: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02). CONCLUSIONS: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.
Assuntos
Anticorpos Antivirais/sangue , Vacina contra Varicela/imunologia , Varicela/complicações , Varicela/imunologia , Infecções por HIV/complicações , Adolescente , Varicela/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Masculino , Prevalência , Estudos SoroepidemiológicosRESUMO
Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load.
Assuntos
Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Prevalência , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Doenças da Boca/complicações , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/virologia , Adolescente , Contagem de Linfócito CD4 , California/epidemiologia , Estudos de Coortes , Coinfecção , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/virologia , Humanos , Masculino , Doenças da Boca/diagnóstico , Doenças da Boca/epidemiologia , Doenças da Boca/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Carga ViralRESUMO
BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort. METHODS: PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months. RESULTS: Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar. CONCLUSIONS: High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/imunologia , Sarampo/imunologia , Caxumba/imunologia , Rubéola (Sarampo Alemão)/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Criança , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Testes de Neutralização , Estados Unidos , Ensaio de Placa ViralRESUMO
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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Complexo AIDS Demência/epidemiologia , Complexo AIDS Demência/mortalidade , Adolescente , Adulto , Fatores Etários , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/mortalidade , Mortalidade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. METHODS: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. RESULTS: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. CONCLUSIONS: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01310023.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Densidade Óssea , Infecções por HIV/tratamento farmacológico , Exposição Materna , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Gravidez , Tenofovir/uso terapêutico , Estados UnidosRESUMO
BACKGROUND: Naegleria fowleri is a climate-sensitive, thermophilic ameba found in warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri-containing water enters the nose, typically during swimming, and migrates to the brain via the olfactory nerve. In August 2013, a 4-year-old boy died of meningoencephalitis of unknown etiology in a Louisiana hospital. METHODS: Clinical and environmental testing and a case investigation were initiated to determine the cause of death and to identify potential exposures. RESULTS: Based on testing of cerebrospinal fluid and brain specimens, the child was diagnosed with PAM. His only reported water exposure was tap water; in particular, tap water that was used to supply water to a lawn water slide on which the child had played extensively prior to becoming ill. Water samples were collected from both the home and the water distribution system that supplied the home and tested; N. fowleri was identified in water samples from both the home and the water distribution system. CONCLUSIONS: This case is the first reported PAM death associated with culturable N. fowleri in tap water from a US treated drinking water system. This case occurred in the context of an expanding geographic range for PAM beyond southern states, with recent case reports from Minnesota, Kansas, and Indiana. This case also highlights the role of adequate disinfection throughout drinking water distribution systems and the importance of maintaining vigilance when operating drinking water systems using source waters with elevated temperatures.
Assuntos
Amebíase/diagnóstico , Amebíase/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Água Potável/parasitologia , Naegleria fowleri/isolamento & purificação , Encéfalo/parasitologia , Líquido Cefalorraquidiano/parasitologia , Pré-Escolar , Evolução Fatal , Humanos , Louisiana , Masculino , OligopeptídeosRESUMO
Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV +), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold-standard assessment in HIV research, they are costly, can overestimate nonadherence and are not practical for routine care. Thus, the development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+youth aged 7-16 (n = 289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/≤ 400 copies/mL. Lower adherence was significantly associated with VL >400 copies/mL across most indicators, including ≥ 1 missed dose in past seven days [youth report: OR = 2.78 (95% CI, 1.46-5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age ≥ 13 years and living with biological mother or relative were associated with VL >400 copies/mL. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Carga Viral , Adolescente , Contagem de Linfócito CD4 , Criança , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Autorrelato , Fatores Socioeconômicos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. Potential mechanisms underlying this observation are unknown. METHODS: The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in third trimester versus none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4-30 days, to compare slopes by TDF exposure. RESULTS: Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 versus -0.08/day (difference -0.50/day [95%CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] versus 26 [22,37] ng/mL). No differences were observed for other biomarkers. CONCLUSIONS: Third trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates.
RESUMO
OBJECTIVE: To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States. DESIGN: Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study. METHODS: First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders. RESULTS: Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular ( n â=â43) and musculoskeletal ( n â=â37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones. CONCLUSIONS: The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.