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ObjectiveTo evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.DesignNonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.MethodsIntensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons.ResultsA total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (n = 18, P

BackgroundHIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study.MethodsWomen with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate.ResultsAmong 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144).ConclusionsRates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women.

BackgroundPregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.MethodsWe compared preterm delivery and birth weight (BW) outcomes (low BW [LBW],

HIV infection progresses rapidly in babies born to HIV-infected women treated with zidovudine. In a study of 291 newborn babies, 70% of babies whose mothers took zidovudine progressed rapidly compared to 30% of babies whose mothers were not treated.

Objective. - To assess the prevalence and prognostic significance of oral lesions in children with human immunodeficiency virus infection. Design. - Clinical cohort study. Setting. - Children's Hospital Center at Jackson Memorial Hospital, Miami, Fla. Participants. - Ninety-nine children with perinatally acquired human immunodeficiency virus infection examined longitudinally for oral lesions. Interventions. - None. Measurements/Main Results. - Presence of oral lesions was determined by a pediatrician who had been trained in the diagnosis of oral lesions. The cumulative prevalence of lesions was 72% for oral candidiasis, 47% for parotid enlargement, and 24% for herpes simplex. The median time from birth to development of a lesion was 2.4 years for candidiasis, 4.6 years for parotid enlargement, and 5 years for herpes simplex. The median time from lesion to death was 3.4 years for patients with candidiasis, 5.4 years for patients with parotid enlargement, and 4.3 years for patients with herpes simplex. In a time-dependent proportional-hazards model, oral candidiasis was associated with a more rapid rate of progression to death (relative hazard, 14.2; 95% confidence interval, 4.8 to 41.8), while parotid enlargement was associated with a less rapid rate of progression to death (relative hazard, 0.38; 95% confidence interval, 0.16 to 0.88) and herpes simplex was unrelated to the rate of progression (relative hazard, 1.3; 95% confidence interval, 0.5 to 3.1). Conclusions. - The presence of oral candidiasis and parotid enlargement confer important prognostic information and should be incorporated into decisions regarding therapy for HIV-infected children. (AJDC. 1993;147:45-48)

The human immunodeficiency virus (HIV) is the causative agent of AIDS. Clinical drug trials have shown that zidovudine (formerly called azidothymidine, or AZT) is effective for the treatment of HIV infection in adults. In order to evaluate the safety, tolerance and effectiveness of zidovudine in children, 88 children (mean age of 4 years) with advanced HIV disease were treated with zidovudine. The first phase of the study included 24 weeks of drug treatment (180 milligrams per square meter of body surface area given every six hours), and those who completed the first phase were allowed to continue receiving zidovudine. During the course of the study, 14 children died due to either pneumonia, lung failure, tuberculosis or heart failure. Sixty-one of the children completed the first phase and 49 of these children continued receiving zidovudine for up to 90 weeks. Sixty-one percent of the children experienced some form of blood toxicity, occurring as anemia (low red blood cell count) in 26 percent of the cases, or neutropenia (low white blood cell count) in 48 percent. Most of these conditions disappeared by themselves. However, 30 children had to have the dose of the drug reduced or required blood transfusions. There were only three cases where drug treatment was stopped because of blood toxicity. Drug treatment with zidovudine resulted in an improvement in mental function and weight gain, and in increase in the number of cerebrospinal fluid cultures that tested negative for HIV. It is concluded that the dose of zidovudine used in this study is can be used safely in children with advanced HIV disease. The clinical improvements observed in this study are similar to those reported previously for zidovudine drug trials in adults infected with HIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

Introduction: Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late‐stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi‐agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. Discussion: Before highly active antiretroviral therapy (HAART), the two‐to‐five‐year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long‐term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV‐infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late‐stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV‐infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV‐uninfected and HIV‐infected children with HIV‐infected mothers. In non‐HIV‐infected infants born to HIV‐infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. Conclusions: Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV‐infected adults and children as cardiovascular illness has become a part of care for long‐term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted., Introduction (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension [1–17]. Cardiac complications often occur in the later [...]

Children with varicella, or chickenpox, who are at risk for developing complications from the disease may benefit from treatment with acyclovir. Acyclovir is not recommended routinely for treatment of chickenpox in children. However, children older than 12, children with lung disorders or chronic skin infections and children whose immune systems may be dysfunctional are candidates for treatment with acyclovir. Treatment with oral acyclovir should begin within the first 24 hours of a child developing the chickenpox rash. A 1991 study found that acyclovir reduced the number of lesions when compared to a placebo, or inactive substance. Only 5% of the treated group developed new lesions by the third day of treatment compared with 20% of the placebo group. The children receiving acyclovir were treated four times each day with 20 milligrams of acyclovir per kilogram of body weight. Side effects were infrequent.

Background Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART). Methods We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20–75 copies/mL) and 1000 copies/mL. All patients were perinatally infected, under 22 years of age, observed for at least 24 months of consecutive follow-up between May 2008 and July 2014, and received their HIV care at the University of Miami Miller School of Medicine. Of the 349 subjects screened, 100 were eligible for analysis. Virological failure was defined as 3 or more consecutive VLs greater than 1000 copies/mL. Multiple logistic regression and receiver operator characteristic curves were used to identify patterns in VL that ultimately resulted in VF. Results Fifteen of the 100 patients experienced VF. Higher log10 mean VL, positive slope of the VL (log10 copies/mL per day), and fewer clinic visits were associated with a higher probability of VF. Sensitivity and specificity were.87 and.95, respectively. Resistance was not found in 12 of 15 patients with VF. Conclusions Patients with LLV that had fewer clinic visits and a trend toward increasing VLs had an increased risk of VF. Noncompliance seems to be a major component of VF. Physicians should emphasize the critical nature of medication adherence. [ABSTRACT FROM AUTHOR]