Long-Term Safety and Effectiveness of Ritonavir, Nelfinavir, and Lopinavir/Ritonavir in Antiretroviral-Experienced HIV-Infected Children
ABSTRACT To evaluate the long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced, initially protease inhibitor (PI)-naive, human immunodeficiency virus (HIV)-1-infected children.
HIV-1-infected children enrolled in the Swiss Mother and Child HIV Cohort Study were eligible for this observational cohort study if they received at least 1 PI of interest between March 1996 and October 2003: ritonavir, nelfinavir, or lopinavir/ritonavir. Data regarding demographics, clinical disease and antiretroviral treatment history, HIV-1 RNA copies/mL, CD4 T-cell counts [absolute (cells/microL) and percentages (%)], adverse events, clinical laboratory values, reasons for discontinuation of PIs, and concomitant medications were extracted from the database for PI-naive (first-line) and PI-experienced (second- or higher-line) PI use.
The total duration of ritonavir, nelfinavir, and lopinavir/ritonavir use for 133 HIV-1-infected children was 163.8, 235.0, and 46.1 patient-years, respectively. In an on-treatment analysis, first-line therapy with any of the PIs significantly reduced HIV-1 concentrations and increased CD4 T-cell counts and percentages from baseline throughout the 288-week study (P <or= 0.05) for ritonavir and nelfinavir and throughout 84 weeks of use for lopinavir/ritonavir, which was introduced into treatment more recently. All PIs investigated were most effective in PI-naive children. Thirteen PI-associated toxicities occurred requiring treatment changes or interruptions (neurologic symptoms, n = 2; pancreatitis, n = 1; allergic reactions, n = 4; visual symptoms, n = 3; and hyperlipidemia, n = 3).
Long-term PI-based therapy seems to be safe and to result in durable virologic and immunologic effectiveness in HIV-1-infected antiretroviral-experienced children.
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- "Numerous adult and pediatric studies have shown a high virologic potency, an excellent toxicity profile and a high barrier to develop resistance.9 However, LPV/r has several limitations, such as poor tolerability of the oral suspension, difficult dosing requirements and undesirable metabolic side effects, especially hyperlipidemia which has unknown consequences as the child grows into adulthood.10–12 "
ABSTRACT: Lopinavir/ritonavir (LPV/r) is considered by many as the first choice protease inhibitor (PI) for children. This co-formulation avoids the need for children to take ritonavir separately to "boost" the levels of lopinavir. LPV/r has high virologic potency, an excellent toxicity profile and a high barrier to the development of viral resistance. However, LPV/r has poor tolerability of the oral suspension (due to the poor taste of ritonavir), difficult dosing requirements and metabolic side effects, especially hyperlipidemia. The new tablet low-dose formulation (100/25 mg) may allow more convenient antiretroviral treatment in children. Novel strategies of LPV/r in childhood could maximize its advantages. For example, infants infected with HIV despite single dose Nevirapine after birth need effective combination antiretroviral treatment. This can be given using a higher dose of LPV/r with therapeutic drug monitoring. Other novel uses include once daily LPV/r regimens in older children and adolescents and lower doses of LPV/r in certain populations, which may decrease hyperlipidemia. Heavily pre-treated children might benefit from a double PI/r regimen which includes LPV/r. The high potency of LPV/r needs to be balanced with convenient regimens, to enhance adherence and decrease toxicity whenever possible. The aim of this review is to discuss the rationale behind these novel strategies of LPV/r use in pediatric antiretroviral treatment as well as their results and limitations.HIV/AIDS - Research and Palliative Care 03/2010; 2:59-67.
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ABSTRACT: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated. Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported. TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.AIDS (London, England) 10/2008; 22(14):1789-98. DOI:10.1097/QAD.0b013e32830c481b · 5.55 Impact Factor
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ABSTRACT: Significant advances have been made in the treatment of human immunodeficiency virus (HIV) infection over the past two decades. Improved therapy has prolonged survival and improved clinical outcome for HIV-infected children and adults. Sixteen antiretroviral (ART) medications have been approved for use in pediatric HIV infection. The Department of Health and Human Services (DHHS) has issued "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection", which provide detailed information on currently recommended antiretroviral therapies (ART). However, consultation with an HIV specialist is recommended as the current therapy of pediatric HIV therapy is complex and rapidly evolving.Therapeutics and Clinical Risk Management 07/2009; 5(3):469-84. DOI:10.2147/TCRM.S4594 · 1.47 Impact Factor