Reader TTS

ABSTRACT 957 _Poster Session IV, Tuesday, 5/4 (poster 101)_ There is limited information on the pharmacodynamic relationship of antiretroviral agents to HIV-1 viral load response in children

receiving HAART. Intensive NFV pharmacokinetics (PK) was performed 4 weeks after randomization to 3 of 4 protocol treatment arms containing NFV in antiretroviral experienced children aged

≥4 months to 17 years enrolled in PACTG 377. Association of the NFV PK with HIV-1 RNA response at weeks 4, 8, and 12 was evaluated in these children. NFV concentrations were determined using

a validated HPLC assay and PK parameters estimated using noncompartmental methods. Suppression of HIV replication was monitored by quantitative HIV-1 RNA PCR measurement (Roche Amplicor).

Responses were assessed in 38 children receiving NFV with PK data available, including 7 receiving NFV BID. NFV AUC or Cmin (typically obtained 10-15 hours following TID dosing) were

correlated with % of children with virologic success, undetectable HIV-1 RNA (<400 copies) at week 12 or a change in RNA from baseline to week 12. Correlation of baseline characteristics

with viral response at week 12 in the 96 children (including the 38 with PK data available) assigned to a NFV-containing treatment arm revealed that baseline viral load was strongly

associated, p<0.001, with virologic success. Univariate analysis of PK parameters in the 38 children with PK indicated an association of very low (≤150) NFV Cmin at week 4 with proportion

with undetectable RNA at week 8 (13% vs. 62%), p=0.019 and week 12 (13% vs. 73%), p=0.003. Correlation of NFV AUC with viral response did not achieve statistical significance at these

timepoints. Multivariate analysis in this group of children confirmed that baseline viral load in a logistic model correlated with viral response, p=0.028, whereas NFV Cmin did not, p=0.39.

Additional analysis indicated that a higher proportion, 71% (12/17), of small children (<25 kg) achieved lower Cmin (≤ median of the entire Pk group) than children ≥25 kg, 33% (7/21), but

was of borderline statistical significance (p=0.049 by Fisher's exact test) in this preliminary analysis. We conclude that high baseline viral load was a strong predictor of viral

response and that very low NFV Cmin values at week 4 were associated with a low rate of undetectable RNA at week 12. This association of a lower rate of virologic success with very low Cmin

may reflect problems with adherence or prolonged overnight dosing intervals in children on TID dosing with resulting low trough levels may suggest closer adherence to TID dosing or support

BID dosing to improve response. This evaluation is not definitive but suggests that the NFV dose may be low for children <25 kg, although viral response did not vary with weight. Analysis

of children subsequently enrolled on this protocol is ongoing. Further correlation of viral response to measures of NFV and other antiretroviral agent exposure is needed. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Pediatrics, Med. Univ. of SC, Charleston, SC, SDAC, Harvard Univ., Boston, MA George M Johnson, Kenneth Stanley, Andrew Wiznia, Paul Krogstad, Sophia Lee, 

Francesca Aweeka, Sandra Hayashi & Sharon A Nachman * Pediatrics, Bronx Lebanon Hospital, Bronx, NY George M Johnson, Kenneth Stanley, Andrew Wiznia, Paul Krogstad, Sophia Lee, Francesca

Aweeka, Sandra Hayashi & Sharon A Nachman * Pediatrics, Univ. of CA, Los Angeles, CA, Sch. of Pharm., Univ. of CA, San Francisco, CA George M Johnson, Kenneth Stanley, Andrew Wiznia, 

Paul Krogstad, Sophia Lee, Francesca Aweeka, Sandra Hayashi & Sharon A Nachman * Pediatrics, SUNY H.S.C., Stony Brook, NY George M Johnson, Kenneth Stanley, Andrew Wiznia, Paul Krogstad,

 Sophia Lee, Francesca Aweeka, Sandra Hayashi & Sharon A Nachman Authors * George M Johnson View author publications You can also search for this author inPubMed Google Scholar * Kenneth

Stanley View author publications You can also search for this author inPubMed Google Scholar * Andrew Wiznia View author publications You can also search for this author inPubMed Google

Scholar * Paul Krogstad View author publications You can also search for this author inPubMed Google Scholar * Sophia Lee View author publications You can also search for this author

inPubMed Google Scholar * Francesca Aweeka View author publications You can also search for this author inPubMed Google Scholar * Sandra Hayashi View author publications You can also search

for this author inPubMed Google Scholar * Sharon A Nachman View author publications You can also search for this author inPubMed Google Scholar CONSORTIA PACTG 377 TEAM RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Johnson, G., Stanley, K., Wiznia, A. _et al._ Preliminary Evaluation of Nelfinavir (NFV) Pharmacodynamics in Stable

Antiretroviral Experienced HIV-Infected Children Following Initiation of HAART (PACTG 377). _Pediatr Res_ 45, 164 (1999). https://doi.org/10.1203/00006450-199904020-00974 Download citation *

Issue Date: 01 April 1999 * DOI: https://doi.org/10.1203/00006450-199904020-00974 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative