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Publications and source records attributed to Russell Van Dyke.
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OBJECTIVE: To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus. DESIGN: Prospective cohort study. SETTING: Pediatric AIDS Clinical Trials Group 219C cohort. PARTICIPANTS: From September 15, 2000, to August 31, 2003, 1927 children perinatally infected with human immunodeficiency virus and receiving HAART were followed up. Main Exposures Age at initiating HAART, duration of HAART use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load. MAIN OUTCOME MEASURES: Incidence rates for Centers for Disease Control and Prevention OI category B and OI category C events were calculated. The association between main exposures and OI occurrence was estimated using proportional hazards regression. RESULTS: Of 1927 subjects, 226 (12.7%) developed OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95% confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100 person-years (95% confidence interval, 1.12-1.91) for first OI category C events. Duration of HAART use was not related to OI risk. Older age (age >10 years) at HAART initiation was associated with increased risk of a first OI (hazard ratio, 2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in children younger than 2 years. This increased risk diminished after adjusting for CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention disease category at HAART initiation. More children with OIs than without OIs had a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of children with OIs vs 7.7% of children without OIs), and at the end of follow-up (41.2% of children with OIs vs 8.3% of children without OIs). CONCLUSIONS: Opportunistic illnesses are occurring in the pediatric human immunodeficiency virus population in the HAART era, mainly in children with persistently low CD4+ T-lymphocyte percentages. Lack of a sustained response to HAART rather than age at or duration of HAART use is predictive of OI risk.
CONTEXT: Antiretroviral therapy (ART) for pediatric human immunodeficiency virus (HIV) infection has evolved from simple nucleoside reverse transcriptase inhibitor (NRTI) regimens to complex combination therapies based largely on evidence from clinical trials. However, the integration of novel ART into the clinical care of pediatric HIV infection has not been examined. OBJECTIVES: To describe changes in the treatment of pediatric HIV infection in the United States from 1987-2003, to assess concordance of initial regimens with US pediatric guidelines, and to identify predictors of the first regimen switch. DESIGN, SETTING, AND PARTICIPANTS: The study population included 766 perinatally HIV-infected children in the Pediatric AIDS Clinical Trials Group 219C cohort born before January 1, 2004, who had not participated in an ART clinical trial at 219C enrollment or during follow-up. MAIN OUTCOME MEASURES: Proportion of children receiving specific ART regimens, proportion of children initiating ART according to pediatric guidelines, and time to first regimen switch (risk of switching). RESULTS: Single and dual NRTI regimens were used most frequently through 1997. In 1998, 2 years after protease inhibitors were approved for adult HIV infection and at the time pediatric guidelines were issued, regimens of highly active antiretroviral therapy including a protease inhibitor became most frequently used. From 1998-2003, 22% of children initiated ART with a regimen not recommended by pediatric guidelines. In multivariate regression, the risk of switching decreased with age at ART initiation (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99) and increased with year of initiation (HR, 1.28; 95% CI, 1.23-1.33). The risk of switching was higher in children who started with 1 NRTI (HR, 8.05; 95% CI, 5.80-11.18), 2 NRTIs (HR, 4.08; 95% CI, 3.08-5.40), or an unconventional regimen (HR, 6.23; 95% CI, 3.36-11.54) vs children who started with a protease inhibitor-containing regimen; and in children who initiated ART at CD4 T lymphocyte percentages less than 15 vs 15 or greater (HR, 2.90; 95% CI, 1.03-8.13). CONCLUSIONS: There was a short lag between the identification of novel ART and its adoption in the pediatric community. A variety of regimens were used, including some unorthodox therapies. Important predictors of first regimen switch were identified.
In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congenitally acquired infections among both HIV-exposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. Compared with opportunistic infections among HIV-infected adults, which are often caused by reactivation of pathogens acquired before HIV infection when host immunity was intact, opportunistic infections among children often reflect primary acquisition of the pathogen and, among children with perinatal HIV infection, infection acquired after HIV infection has been established and begun to compromise an already immature immune system. Laboratory diagnosis of opportunistic infections can be more difficult with children. Finally, treatment recommendations should consider differences between adults and children in terms of drug pharmacokinetics, dosing, formulations, administration, and toxicities. This report focuses on treatment of opportunistic infections that are common in HIV-exposed and infected infants, children, and adolescents in the United States.
In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congentially acquired infections among both HIV-exposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. Compared with opportunistic infections among HIV-infected adults, which are often caused by reactivation of pathogens acquired before HIV infection when host immunity was intact, opportunistic infections among children often reflect primary acquisition of the pathogen and, among children with perinatal HIV infection, infection acquired after HIV infection has been established and begun to compromise an already immature immune system. Laboratory diagnosis of opportunistic infections can be more difficult with children. Finally, treatment recommendations should consider differences between adults and children in terms of drug pharmacokinetics, dosing, formulations, administration, and toxicities. This report focuses on treatment of opportunistic infections that are common in HIV-exposed and infected infants, children, and adolescents in the United States.
CONTEXT: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis. OBJECTIVES: To determine the feasibility and acceptance of rapid HIV testing among women in labor and to assess rapid HIV assay performance. DESIGN, SETTING, AND PATIENTS: The Mother-Infant Rapid Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and voluntary rapid HIV testing for women in labor at 16 US hospitals from November 16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood was used. MAIN OUTCOME MEASURES: Acceptance of HIV testing; sensitivity, specificity, and predictive value of the rapid test; time from blood collection to patient notification of results. RESULTS: There were 91,707 visits to the labor and delivery units in the study, 7381 of which were by eligible women without documentation of HIV testing. Of these, 5744 (78%) women were approached for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test were 100% and 99.9%, respectively; positive predictive value was 90% compared with 76% for enzyme immunoassay (EIA). Factors independently associated with higher test acceptance included younger age, being black or Hispanic, gestational age less than 32 weeks, and having had no prenatal care. Lower acceptance was associated with being admitted between 4 pm and midnight, particularly on Friday nights, but this may be explained in part by fewer available personnel. Median time from blood collection to patient notification of result was 66 minutes (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001). CONCLUSIONS: Rapid HIV testing is feasible and delivers accurate and timely test results for women in labor. It provides HIV-positive women prompt access to intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal HIV transmission, and may be particularly applicable to higher-risk populations.
The physiologic changes that occur during pregnancy make it difficult to predict antiretroviral pharmacokinetics (PKs), but few data exist on the PKs of protease inhibitors in human immunodeficiency virus (HIV)-infected pregnant women. The objective of the present study was to determine the PKs of ritonavir (RTV)-enhanced saquinavir (SQV) in HIV-infected pregnant women by an area under the curve (AUC)-targeted approach. A phase I, formal PK evaluation was conducted with HIV-infected pregnant woman during gestation, during labor and delivery, and at 6 weeks postpartum. The SQV-RTV regimen was 800/100 mg twice a day (b.i.d.), and nucleoside analogs were administered concomitantly. The SQV exposure targeted was an AUC at 24 h of 10,000 ng. h/ml. Participants were evaluated for 12-h steady-state PKs at each time period. Thirteen subjects completed the PK evaluations during gestation, 7 completed the PK evaluations at labor and delivery, and 12 completed the PK evaluations postpartum. The mean baseline weight was 67.4 kg, and the median length of gestation was 23.3 weeks. All subjects achieved SQV exposures in excess of the target AUC. The SQV AUCs at 12 h (AUC(12)s) during gestation (29,373 +/- 17,524 ng. h/ml [mean +/- standard deviation]), during labor and delivery (26,189 +/- 22,138 ng. h/ml), and during the postpartum period (35,376 +/- 26,379 ng. h/ml) were not significantly different. The mean values of the PK parameters for RTV were lower during gestation than during the postpartum period: for AUC(12), 7,811 and 13,127 ng. h/ml, respectively; for trough concentrations, 376 and 632 ng/ml, respectively; and for maximum concentrations, 1,256 and 2,252 ng/ml, respectively (P </= 0.05 for all comparisons). This is the first formal PK evaluation of a dual protease inhibitor regimen with HIV-infected pregnant women. The level of SQV exposure was sufficient at each time of evaluation. These data demonstrate large variability in SQV and RTV concentrations and suggest that RTV concentrations are altered by pregnancy. These PK results suggest that SQV-RTV at 800/100 mg b.i.d. appears to be a reasonable treatment option for this population.