Sophia Lee

Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children : Week 24 results of a randomized controlled trial-PACTG 377

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Immunologic response to combination nucleoside analogue plus protease inhibitor therapy in stable antiretroviral therapy-experienced human immunodeficiency virus-infected children.

The response of 40 immunologic parameters was studied for 147 clinically stable, protease inhibitor-naive, human immunodeficiency virus (HIV)-infected children aged 2-17 years when antiretroviral therapy was changed to either a dual nucleoside analogue regimen or a protease inhibitor-containing regimen. Immunologic response to therapy, as measured by lymphocyte subsets, 3-color flow cytometric measures, and lymphoproliferative assays, were investigated for changes in weeks 44 and 48. The most significant changes after baseline that were associated with the administration of a protease inhibitor-containing regimen were seen for percentages of CD8(+)/CD38(+)/HLA-DR(+), CD8(+)/CD95(+)/CD28(-), and CD8. The percentages of CD8(+)/CD38(+)/HLA-DR(+) and CD8(+)/CD95(+)/CD28(-) decreased from baseline medians of 33% and 46% to medians of 18% and 30% at week 44 (P<.0001 for both). Median CD4 cell count increased 168 cells/microL (from 694 cells/microL to 862 cells/microL; P=.02) by week 48 in this clinically stable population. Changes in lymphoproliferative responses to HIV antigens and recall antigens did not increase over time and between groups.

Comparison of responses to pituitary adenylate cyclase activating peptides 38 and 27 in the pulmonary vascular bed of the cat

Responses to pituitary adenylate cyclase activating polypeptide (PACAP)-38 were investigated and compared with responses to PACAP-27 and vasoactive intestinal polypeptide (VIP) in the pulmonary vascular bed of the intact-chest cat under constant flow conditions. Under low resting tone baseline conditions, injections of PACAP-38 had little or no effect on lobar arterial pressure; however, when tone in the pulmonary vascular bed was raised to a high steady level (35-40 mm Hg) with U46619, intralobar injections of PACAP-38 caused dose-related decreases in lobar arterial pressure without altering left atrial pressure. The peptide induced biphasic changes in systemic arterial pressure. PACAP-38 was more potent than VIP in decreasing lobar arterial pressure, and both peptides were significantly less potent than PACAP-27 in dilating the pulmonary vascular bed. The present data show that PACAP-38 has significant vasodilator activity in the pulmonary vascular bed of the cat, and that the 27 amino acid form of the peptide is approximately 3-fold more potent than PACAP-38.

Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection.

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.

Preliminary Evaluation of Nelfinavir (NFV) Pharmacodynamics in Stable Antiretroviral Experienced HIV-Infected Children Following Initiation of HAART (PACTG 377)

Preliminary Evaluation of Nelfinavir (NFV) Pharmacodynamics in Stable Antiretroviral Experienced HIV-Infected Children Following Initiation of HAART (PACTG 377)