RESUMEN
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.
Asunto(s)
Infecciones por VIH , Adolescente , Niño , Estudios de Cohortes , Humanos , Pruebas Serológicas , Carga Viral , ViremiaRESUMEN
BACKGROUND: Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). METHODS: An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. RESULTS: Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1. CONCLUSIONS: VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.
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Antirretrovirales/administración & dosificación , Anticuerpos Monoclonales/farmacocinética , Anticuerpos ampliamente neutralizantes/farmacología , Anticuerpos Anti-VIH , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antirretrovirales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos ampliamente neutralizantes/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Anticuerpos Anti-VIH/administración & dosificación , Anticuerpos Anti-VIH/efectos adversos , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , VIH-1/inmunología , VIH-1/patogenicidad , Semivida , Humanos , Recién Nacido , MasculinoRESUMEN
No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD improved with 48 weeks of alendronate and continued to improve with an additional 48 weeks of therapy. Gains were largely maintained 48 weeks after stopping alendronate.
Asunto(s)
Conservadores de la Densidad Ósea , Enfermedades Óseas Metabólicas , Infecciones por VIH , Adolescente , Alendronato/efectos adversos , Densidad Ósea , Niño , Estudios Cruzados , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , HumanosRESUMEN
Prematurity remains a major cause of morbidity and mortality. Research to prevent preterm birth and improve treatments for preterm infants involves both intramural and extramural research, not just at the National Institute of Child Health and Human Development, but across many institutes and centers at the National Institutes of Health.
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Displasia Broncopulmonar , Neumonía , Nacimiento Prematuro , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Niño , Femenino , Salud Global , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , National Institutes of Health (U.S.) , Embarazo , Nacimiento Prematuro/prevención & control , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Although mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission. METHODS: A Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis. RESULTS: Forty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding. CONCLUSIONS: Subcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos ampliamente neutralizantes/administración & dosificación , Anticuerpos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , África , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos ampliamente neutralizantes/efectos adversos , Femenino , Anticuerpos Anti-VIH/efectos adversos , Infecciones por VIH/sangre , Humanos , Recién Nacido , Inyecciones Subcutáneas , Modelos Lineales , Masculino , Estados UnidosRESUMEN
BACKGROUND: Children and adolescents with perinatal human immunodeficiency virus (HIV) infection and with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in youths living with HIV. METHODS: Fifty-two children and adolescents (aged 11-24 years) perinatally infected with HIV with low lumbar spine (LS) BMD (Z score < -1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the United States and Brazil. All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial. RESULTS: Grade 3 or higher abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (P > .99). No cases of jaw osteonecrosis, atrial fibrillation, or nonhealing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate (20% [14%-25%]) than placebo (7% [5%-9%]) (P < .001). Similar improvements were seen for whole body BMD. CONCLUSIONS: In this small study in children and adolescents perinatally infected with HIV with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone. CLINICAL TRIALS REGISTRATION: NCT00921557.
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Conservadores de la Densidad Ósea , Enfermedades Óseas Metabólicas , Infecciones por VIH , Adolescente , Adulto , Alendronato/uso terapéutico , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Brasil , Niño , Estudios Cruzados , Método Doble Ciego , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Adulto JovenRESUMEN
Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods: This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results: Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions: For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. Clinical Trials Registration: NCT01751646.
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Fármacos Anti-VIH/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea/efectos de los fármacos , Colecalciferol/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Columna Vertebral/fisiología , Tenofovir/administración & dosificación , Adolescente , Hormonas y Agentes Reguladores de Calcio , Método Doble Ciego , Femenino , Humanos , Masculino , Placebos/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. METHODS AND FINDINGS: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. CONCLUSION: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.
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Antirretrovirales/uso terapéutico , Transmisión de Enfermedad Infecciosa , Salud Global/estadística & datos numéricos , Infecciones por VIH , Adolescente , Niño , Transmisión de Enfermedad Infecciosa/prevención & control , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Monitoreo Epidemiológico , Femenino , Estudios de Seguimiento , Infecciones por VIH/epidemiología , Infecciones por VIH/mortalidad , Infecciones por VIH/terapia , Infecciones por VIH/transmisión , Humanos , Recién Nacido , Cooperación Internacional , Internacionalidad , Estudios Longitudinales , MasculinoRESUMEN
PURPOSE OF REVIEW: Zika virus' impact on pregnancy became widely known in 2015 with a dramatic increase in the number of babies born with microcephaly in Recife, Brazil. A mosquito-borne virus resulting in congenital anomalies is unique, and Zika's ability to cause neurological defects on a large scale was a grim reminder of the Rubella epidemic in the 1950s. Over the past 2 years, studies have provided insight on how Zika virus (ZIKV) infects cells and causes disease, but much remains unknown about the long-term risks of Zika exposure on infant growth and development. RECENT FINDINGS: The impact of ZIKV on pregnancy extends beyond microcephaly and may only first be identified in infancy. The virus has a long latency in semen and can be transmitted sexually. Transplacental passage occurs through infection of Hofbauer cells in the trophoblast. A major difficulty in management of ZIKV disease is that most infections are asymptomatic and the diagnostic methods are not ideal, making both diagnosis and ascertainment of timing of infection problematic. Several different types of vaccines are in development. Large studies are ongoing to determine the risk and total spectrum of anomalies based on the timing of infection and other environmental exposures. SUMMARY: This review will summarize the epidemic, what we have learned, what we hope to learn, and current recommendations for care and management.
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Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/transmisión , Anomalías Múltiples/virología , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Insectos Vectores , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Semen/virología , Enfermedades Virales de Transmisión Sexual , Infección por el Virus Zika/diagnósticoRESUMEN
Globally 1.8 million children are living with human immunodeficiency virus (HIV), yet only 51% of those eligible actually start treatment. Research and development (R&D) for pediatric antiretrovirals (ARVs) is a lengthy process and lags considerably behind drug development in adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up globally. We review current approaches to R&D for pediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including focusing on a limited number of prioritized formulations and strengthening existing partnerships to ensure that pediatric investigation plans are developed early in the drug development process. Simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more sustainable. Lessons learned from HIV should be shared to support progress in developing pediatric formulations for other diseases, including tuberculosis and viral hepatitis.
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Antirretrovirales/uso terapéutico , Aprobación de Drogas/métodos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/administración & dosificación , Niño , Aprobación de Drogas/economía , Aprobación de Drogas/organización & administración , Combinación de Medicamentos , Composición de Medicamentos , Infecciones por VIH/tratamiento farmacológico , Humanos , Apoyo a la Investigación como AsuntoRESUMEN
BACKGROUND: We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. METHODS: In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups. RESULTS: There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables. CONCLUSIONS: These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group. CLINICAL TRIALS REGISTRATION: NCT01769469.
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Fármacos Anti-VIH/efectos adversos , Densidad Ósea/efectos de los fármacos , Emtricitabina/efectos adversos , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Profilaxis Pre-Exposición , Tenofovir/efectos adversos , Adolescente , Fármacos Anti-VIH/administración & dosificación , Creatinina/sangre , Creatinina/orina , Emtricitabina/administración & dosificación , Factor-23 de Crecimiento de Fibroblastos , Tasa de Filtración Glomerular/efectos de los fármacos , Infecciones por VIH/sangre , Infecciones por VIH/metabolismo , Infecciones por VIH/orina , Humanos , Riñón/efectos de los fármacos , Masculino , Hormona Paratiroidea/sangre , Hormona Paratiroidea/orina , Insuficiencia Renal/inducido químicamente , Tenofovir/administración & dosificación , Adulto JovenRESUMEN
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.
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Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH , VIH-1/efectos de los fármacos , Transmisión Vertical de Enfermedad Infecciosa , Adolescente , Niño , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Lactante , Masculino , Prevalencia , Estudios Prospectivos , Estados Unidos/epidemiologíaRESUMEN
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.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Infecciones por VIH/complicaciones , Enfermedades de la Boca/complicaciones , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/virología , Adolescente , Recuento de Linfocito CD4 , California/epidemiología , Estudios de Cohortes , Coinfección , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/virología , Humanos , Masculino , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/epidemiología , Enfermedades de la Boca/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Carga ViralRESUMEN
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.
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Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Complejo SIDA Demencia/epidemiología , Complejo SIDA Demencia/mortalidad , Adolescente , Adulto , Factores de Edad , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Incidencia , Masculino , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/mortalidad , Mortalidad , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
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.
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Fármacos Anti-VIH/efectos adversos , Densidad Ósea , Infecciones por VIH/tratamiento farmacológico , Exposición Materna , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Tenofovir/efectos adversos , Adulto , Fármacos Anti-VIH/uso terapéutico , Estudios Transversales , Femenino , Humanos , Recién Nacido , Embarazo , Tenofovir/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: Individuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls. METHODS: This is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat. RESULTS: RCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex- and race-matched controls (1.32 ± 0.21 mm vs 1.09 ± 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness. CONCLUSIONS: This investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction.
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Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/patología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Radiografía , Adulto JovenRESUMEN
BACKGROUND: Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. METHODS: The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)-exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. RESULTS: Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. CONCLUSIONS: Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.
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Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Nacimiento Prematuro/epidemiología , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Edad Gestacional , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Embarazo , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Riesgo , Adulto JovenRESUMEN
An alarming proportion of incident human immunodeficiency virus (HIV) infections worldwide occur in youth. In the United States, 69% of all new infections among youth occurred in young men who have sex with men (YMSM). Recent studies show the promise of preexposure prophylaxis (PrEP) for preventing HIV infection, but research efforts suffer from disproportionately low representation of the youth who are most at risk. Youth-focused research is critical and should include behavioral, community, and biomedical interventions to create a comprehensive HIV prevention package. The many ethical, legal, and regulatory considerations in conducting HIV research among, and in providing care services to, youth must be addressed so that those at high risk and most likely to benefit can have unfettered access to safe and effective health-promoting interventions. YMSM and minority youth are at substantial HIV risk and urgently need effective HIV prevention tools for which the short and long-term benefits and risks have been carefully considered.
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Infecciones por VIH/prevención & control , Prevención Primaria/economía , Adolescente , Adulto , Negro o Afroamericano , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Control de Enfermedades Transmisibles/economía , Control de Enfermedades Transmisibles/legislación & jurisprudencia , Femenino , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Humanos , Masculino , Prevención Primaria/ética , Prevención Primaria/legislación & jurisprudencia , Riesgo , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Factors associated with initiation of sexual activity among perinatally human immunodeficiency virus (HIV)-infected (PHIV(+)) youth, and the attendant potential for sexual transmission of antiretroviral (ARV) drug-resistant HIV, remain poorly understood. METHODS: We conducted cross-sectional and longitudinal analyses of PHIV(+) youth aged 10-18 years (mean, 13.5 years) enrolled in the US-based Pediatric HIV/AIDS Cohort Study between 2007 and 2009. Audio computer-assisted self-interviews (ACASI) were used to collect sexual behavior information. RESULTS: Twenty-eight percent (95% confidence interval [CI], 23%-33%) (92/330) of PHIV(+) youth reported sexual intercourse (SI) (median initiation age, 14 years). Sixty-two percent (57/92) of sexually active youth reported unprotected SI. Among youth who did not report history of SI at baseline, ARV nonadherence was associated with sexual initiation during follow-up (adjusted hazard ratio, 2.87; 95% CI, 1.32-6.25). Youth living with a relative other than their biological mother had higher odds of engaging in unprotected SI than those living with a nonrelative. Thirty-three percent of youth disclosed their HIV status to their first sexual partner. Thirty-nine of 92 (42%) sexually active youth had HIV RNA ≥5000 copies/mL after sexual initiation. Viral drug resistance testing, available for 37 of these 39 youth, identified resistance to nucleoside reverse transcriptase inhibitors in 62%, nonnucleoside reverse transcriptase inhibitors in 57%, protease inhibitors in 38%, and all 3 ARV classes in 22%. CONCLUSIONS: As PHIV(+) youth become sexually active, many engage in behaviors that place their partners at risk for HIV infection, including infection with drug-resistant virus. Effective interventions to facilitate youth adherence, safe sex practices, and disclosure are urgently needed.