RESUMO
OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.
Assuntos
Antirretrovirais/administração & dosagem , Infecções por Citomegalovirus/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Adulto , Antirretrovirais/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/congênito , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Soronegatividade para HIV/efeitos dos fármacos , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , Porto Rico/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s is a prospective, nonblinded, pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including 2 cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the second trimester, 400/100 mg during the third trimester, and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by high-performance liquid chromatography. Pharmacokinetic targets were the 10th percentile atazanavir area under the concentration versus time curve (AUC) (29.4 µg·hr·mL·) in nonpregnant adults on standard dose and 0.15 µg/mL, minimum trough concentration. RESULTS: Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; median (range) pharmacokinetic parameters are presented for second trimester, third trimester, and PP and number who met target/total. ATAZANAVIR WITHOUT TENOFOVIR: AUC 30.5 (9.19-93.8), 45.7 (11-88.3), and 48.8 (9.9-112.2) µg·hr·mL, and 8/14, 29/37, and 27/34 met target. C24 h was 0.49 (0.09-4.09), 0.71 (0.14-2.09), and 0.90 (0.05-2.73) µg/mL; 13/14, 36/37, and 29/34 met target. ATAZANAVIR WITH TENOFOVIR: AUC 26.2 (6.8-60.9) (P < 0.05 compared with PP), 37.7 (0.72-88.2) (P < 0.05 compared with PP), and 58.6 (6-149) µg·hr·mL, and 7/17, 23/32, and 27/29 met target. C24 h was 0.44 (0.12-1.06) (P < 0.05 compared with PP), 0.57 (0.02-2.06) (P < 0.05 compared with PP), and 1.26 (0.09-5.43) µg/mL; 7/17, 23/32, and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events. CONCLUSIONS: Atazanavir/ritonavir increased to 400/100 mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Oligopeptídeos/farmacocinética , Organofosfonatos/farmacocinética , Complicações Infecciosas na Gravidez/tratamento farmacológico , Terceiro Trimestre da Gravidez , Piridinas/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/uso terapêutico , Adolescente , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Humanos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Segundo Trimestre da Gravidez , Estudos Prospectivos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To assess the characteristics and outcomes of antiretroviral treatment (ART) interruption (TI) in perinatally HIV-infected children. DESIGN: The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7- to 16-year-old perinatally HIV-infected children between 2007 and 2009 from 15 sites in the United States and Puerto Rico. METHODS: TI was defined as ART discontinuation for ≥ 3 months after ≥ 6 months of continuous ART. Subjects with and without TI were compared. Rates of change (slopes) in CD4 T-lymphocyte (CD4) count and percentage (%) per month during TI were calculated. Factors related to CD4 slope in univariable analyses were included in multivariable linear regression. RESULTS: Of 444 eligible AMP subjects, 101 (23%) had at least one TI. Subjects with TI were born in earlier years but were otherwise similar to those without TI. For 81 TI subjects with complete data, the median (range) CD4% and CD4 count slopes were -0.66% per month (-3.54% to +1.34% per month) and -12.7 cells per cubic millimeter per month (-148 cells/mm to +31 cells/mm per month), respectively. On multivariable linear regression, there was a trend for lower CD4% slope to be associated (P < 0.1) with female sex, higher CD4% at TI, and higher peak viral load before TI. Advanced HIV disease stage and numerous ART regimens were more common in TI subjects in the lowest (fastest declining) CD4% slope quartile. CONCLUSIONS: TIs in perinatally HIV-infected youth are common. During TIs, CD4 values decline on average but with high intersubject variability. Factors predicting CD4 slope during TI need further study.