ABSTRACT
OBJECTIVE: We tested the hypothesis that concentrated formula (CF) begun within the first 2 weeks of life increases growth in infants born to human immunodeficiency virus (HIV)-infected mothers. MATERIALS AND METHODS: HIV-exposed infants from the United States, the Bahamas, and Brazil were randomized in a double-blind, controlled trial to receive either a CF (87 kcal/100 mL [26 kcal/oz]) or a standard formula (SF; 67 kcal/100 mL [20 kcal/oz]) for 8 weeks. This article presents results for infants who were not determined to be HIV infected based on testing at 4 weeks. Primary outcomes were safety, tolerability, and growth in weight and length. RESULTS: Two thousand ninety-seven infants were enrolled, of whom 1998 were uninfected and had study formula dispensed. At weeks 4 and 8, uninfected infants receiving CF showed higher energy intake than those who were receiving SF (P < 0.001). By week 8, uninfected infants assigned to CF weighed more than infants receiving SF. There were no consistent differences in measures of tolerability, and rates of discontinuation or perceived formula intolerance were similar between treatment groups. CONCLUSIONS: A CF is well tolerated and results in increased weight gain compared with SF. Until the HIV status of an infant is reliably determined, early introduction of a CF in HIV-exposed children may have beneficial effects on growth. The role of early nutritional intervention remains to be determined for individuals living in countries with endemic malnutrition for whom formula feeding is a viable option.
Subject(s)
Energy Intake , HIV Infections , Infant Formula , Pregnancy Complications, Infectious , Weight Gain , Animals , Bahamas , Brazil , Double-Blind Method , Female , HIV Infections/transmission , Humans , Infant , Infant Formula/chemistry , Infant, Newborn , Milk , Pregnancy , United StatesABSTRACT
BACKGROUND: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. METHODS: As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14. RESULTS: The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels <100 ng/mL, although only 1 neonate had no detectable NVP. CONCLUSION: Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.
Subject(s)
HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Nevirapine/therapeutic use , Pregnancy Complications, Infectious/virology , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/therapeutic use , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Female , HIV Infections/transmission , HIV-1/drug effects , Humans , Infant, Newborn , Nevirapine/blood , Nevirapine/pharmacokinetics , Pregnancy , Treatment Outcome , Viral LoadABSTRACT
Saquinavir boosted with low-dose ritonavir given with zidovudine and lamivudine was well tolerated by pregnant women and their infants. All mothers had <400 human immunodeficiency virus type 1 RNA copies/ml at delivery. Two had elevated liver transaminases and amylase. Seven infant adverse events were possibly treatment related (anemia, neutropenia, and hyperbilirubinemia).
Subject(s)
Anti-HIV Agents , HIV Infections/drug therapy , Pregnancy Complications, Infectious/drug therapy , Reverse Transcriptase Inhibitors , Ritonavir , Saquinavir , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Drug Therapy, Combination , Female , HIV Infections/virology , HIV-1/drug effects , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Microbial Sensitivity Tests , Mothers , Pregnancy , Pregnancy Complications, Infectious/virology , RNA, Viral/blood , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/therapeutic use , Ritonavir/administration & dosage , Ritonavir/adverse effects , Ritonavir/therapeutic use , Saquinavir/administration & dosage , Saquinavir/adverse effects , Saquinavir/therapeutic use , Treatment OutcomeABSTRACT
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
Subject(s)
Anti-HIV Agents/pharmacokinetics , HIV Infections/metabolism , Ritonavir/pharmacokinetics , Saquinavir/pharmacokinetics , Adult , Anti-HIV Agents/administration & dosage , Area Under Curve , Delivery, Obstetric , Drug Combinations , Female , Half-Life , Humans , Labor, Obstetric , Postpartum Period , Pregnancy , RNA, Viral/analysis , RNA, Viral/blood , Ritonavir/administration & dosage , Saquinavir/administration & dosageABSTRACT
BACKGROUND: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. METHODS: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. FINDINGS: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. INTERPRETATION: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
Subject(s)
Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1 , Adolescent , Age Factors , Child , Child, Preschool , Cohort Studies , Disease Progression , Drug Administration Schedule , Female , Follow-Up Studies , HIV Infections/immunology , HIV Infections/virology , HIV Protease Inhibitors/pharmacology , HIV-1/drug effects , Humans , Male , Survival Analysis , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: The efficacy and tolerance of switching from zidovudine (ZDV) and lamivudine (3TC) in clinically stable HIV-infected children with incomplete viral suppression to stavudine (d4T), nevirapine (NVP) and ritonavir (RTV) has not been determined. Aim. To evaluate the safety, tolerance, antiviral activity and immunologic changes after the change to a three drug combination. METHODS: During a clinical trial in which HIV-infected antiretroviral-experienced children were initially randomized to receive d4T/RTV, ZDV/3TC/RTV or ZDV/3TC (Step 1), 48 children who had HIV RNA > or = 10,000 copies/ml after > or = 12 weeks of ZDV/3TC therapy in Step 1 were switched to d4T/NVP/RTV in Step 2. The proportion of children receiving therapy with HIV RNA < or = 400 copies/ml at Study Weeks 24 and 48 receiving d4T/NVP/RTV in Step 2 were compared with children receiving RTV-containing regimens in Step 1. RESULTS: At 24 weeks of treatment with d4T/NVP/RTV in Step 2, 48% (23 of 48) of children had HIV RNA < or = 400 copies/ml compared with 34% (31 of 92) and 47% (44 of 93) receiving d4T/RTV or ZDV/3TC/RTV for 24 weeks in Step 1; at 48 weeks virologic response was 44, 27 and 42% in Step 2 d4T/NVP/RTV, Step 1 d4T/RTV and Step 1 ZDV/3TC/RTV arms, respectively. CONCLUSIONS: A delay of 7 to 12 months in the initiation of protease inhibitor-containing combination therapy in children receiving dual nucleoside analogue therapy did not adversely affect the RNA response during the first 48 weeks of treatment.
Subject(s)
Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacology , HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/pharmacology , Nevirapine/administration & dosage , Nevirapine/pharmacology , Stavudine/administration & dosage , Stavudine/pharmacology , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Infant , Male , RNA, Viral/analysis , Treatment Outcome , Viral LoadABSTRACT
Se observó la respuesta a la nifedipina sublingual en 7 pacientes pediátricos con enfermedad renal e hipertensión aguda severa. La dosis promedio fue de 0.21mg/Kg, evidenciándose una respuesta ya a los 3 min., con un efecto hipotensor mayor ocurrido en los primeros 30 min., pero continuando su efecto hasta los 60-120 min. La droga fue ien tolerada, de rápida acción y sugiere ser eficaz en el manejo de niños y adolescentes con hipertensión secundaria aguda. No se observaron efectos adversos sericos
Subject(s)
Humans , Infant, Newborn , Child , Adolescent , Hypertension/drug therapy , Nifedipine/administration & dosage , Administration, Sublingual , Capsules , Drug Evaluation , Hypertension/metabolism , Hospitals, General , Nifedipine/adverse effects , Nifedipine/pharmacokinetics , Puerto Rico , Time FactorsABSTRACT
El Departamento de Pediatría del Hospital Municipal de san Juan participó en un estudio clínico colaborativo, placebo controlado, diseñado por NICHD con el propósito de determinar si el uso de la GIIV es efectiva en prevenir infecciones serias en niños sintomáticos con infección por VIH. De los 372 niños randomizados, 33% fueron del Hospital Municipal de san Juan. De los 16 niños en placebo, 9 (56%) desarrollaron 23 episodios de infecciones severas y 4 de 15 niños en GIIV desarrollaron cinco episodios (33%). Hubo hospitalizaciones en el grupo placebo y 6 en el grupo GIIV. La mortalidad en nuestro centro fue de 12%. En el Hospital Municipal de San Juan no se registraron reacciones adversas a las infusiones. La GIIV demostró ser efectiva en prevenir infecciones bacterianas y disminuir el número de hospitalizaciones en un subgrupo de niños infectados con el VIH
