Risk Factors for Perinatal Transmission of Hepatitis C Virus.

OBJECTIVE: To estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission. METHODS: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) and at 18-24 months (HCV RNA and antibody testing) of life. The primary outcome was perinatal transmission, defined as positive test results at either follow-up time point. RESULTS: A total of 109,379 individuals were screened for HCV infection. Of the 1,224 participants who screened positive, 772 (63.1%) enrolled and 432 of those 772 (56.0%) had data available to assess primary outcome. The overall rate of perinatal transmission was 6.0% (26/432, 95% CI 4.0-8.7%). All children with HCV infection were born to individuals with demonstrable viremia. In viremic participants (n=314), the perinatal transmission rate was 8.0% (95% CI 5.2-11.5%). Risk factors for perinatal transmission included HCV RNA greater than 106 international units/mL (adjusted odds ratio [aOR] 8.22, 95% CI 3.16-21.4) and vaginal bleeding reported at any time before delivery (aOR 3.26, 95% CI 1.32-8.03). A viremic threshold for perinatal transmission could not be established. CONCLUSION: Perinatal transmission of HCV infection was limited to viremic individuals. High viral loads and antepartum bleeding were associated with perinatal transmission.

CD4+ lymphocyte-based immunologic outcomes of perinatally HIV-infected children during antiretroviral therapy interruption.

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.

Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects.

OBJECTIVES: The purpose of this work was to obtain long-term safety and efficacy data for antiretroviral regimens containing emtricitabine in HIV-infected pediatric subjects and confirm that a pediatric dose of 6 mg/kg once daily would provide steady-state emtricitabine concentrations comparable to those observed in adults given 200 mg of emtricitabine once daily. PATIENTS AND METHODS: HIV-infected subjects between 3 months and 16 years of age were enrolled, including 71 antiretroviral-naïve subjects and 45 antiretroviral-experienced subjects. Naive subjects received emtricitabine plus stavudine plus lopinavir or ritonavir. Experienced subjects replaced the lamivudine in their existing regimens with emtricitabine. Tolerance, safety, disease progression, and virologic and immunologic responses were evaluated. RESULTS: The Kaplan-Meier probability of persistent virologic response in the intent-to-treat population through week 164 at < or = 400 copies per mL and < or = 50 copies per mL was 74% and 62%, respectively. Three subjects (3%) discontinued the study for adverse events, 8 (7%) for virologic failure, and 1 died through a median follow-up of 164 weeks. The annualized incidence rate of grade 3 to 4 adverse events and grade 3 to 4 laboratory abnormalities was 6% and 3%, respectively. The annualized incidence rate of serious adverse events was 9%, with 1% attributed as related to emtricitabine. Genotypic analysis showed the emergence of the M184V mutation in 4 of the 15 subjects who experienced virologic failure through week 164. Pharmacokinetic evaluation demonstrated plasma drug exposures in these children comparable to adults receiving the approved dose of 200 mg once daily. CONCLUSIONS: These results demonstrate the safety and efficacy of emtricitabine in pediatric patients. They also support that the safety and efficacy profile of emtricitabine in children is similar to that demonstrated in adults.