468   Analysis of HIV-1 Drug Resistance in a Randomized, Controlled Trial of a Combination of Nucleoside Analog Reverse Transcriptase (RT) Inhibitors Plus Nevirapine (NVP), Nelfinavir (NFV), or Ritonavir (RTV) in Stable Antiretroviral Therapy- Experienced HIV-Infected Children.

S. H. Eshleman*¹, P. Krogstad², J. B. Jackson¹, S. Lee³, Y. G. Wang³, L. J. Wei³, S. Cunningham¹, M. Wantman³, C. Lindquist⁴, S. Nachman⁵, and P. Palumbo⁶for the PACTG 377 Study Team.
¹Johns Hopkins Med. Inst., Baltimore, MD,²Univ. of California at Los Angeles;³Harvard Sch. of Publ. Hlth., Boston, MA;⁴Applied Biosystems, Foster City, CA;⁵State Univ. of New York at Stony Brook; and⁶Univ. of Med. & Dentistry of New Jersey, Newark.

Background:In PACTG 377, children were randomized to 4 treatment arms including different combinations of stavudine, lamivudine (3TC), NVP, NFV, or RTV. Prior treatment with zidovudine (AZT), zalcitabine (ddC), or didanosine (ddI) was acceptable. We examined HIV-1 drug resistance (^R) mutations in these children prior to study treatment (baseline) and at virologic failure.

Methods:Children were divided into failure and non-failure groups. The non-failure group included 71 children with satisfactory initial virologic suppression and sustained suppression for 48 weeks. The failure group included 70 children with unsatisfactory initial virologic suppression or subsequent virologic rebound. Genotyping was performed with the Applied Biosystems ViroSeq HIV-1 Genotyping System.

Results:AZT^R, ddI^R, and ddC^Rmutations were frequently detected at baseline but were not associated with virologic failure. NVP^Rand 3TC^Rmutations were detected at significantly higher rates at the time of virologic failure. NVP^Rmutations at failure were significantly more common among children receiving 3-drug vs. 4-drug NVP-containing regimens. Children who were maintained on their initial study regimen after virologic failure accumulated additional mutations after 20 to 48 weeks on therapy, including RTV^Rand NFV^Rmutations.

Conclusions:Antiretroviral treatment in PACTG 377 was associated with selection of NVP^Rand 3TC^Rmutations in children who experienced virologic failure. Selection of NVP^Rmutations was less common among children receiving a 4-drug NVP-containing regimen. NFV^Rand RTV^Rmutations were rarely detected at the time of failure. However, those mutations, as well as additional NVP^Rand 3TC^Rmutations, were frequently selected in children who were maintained on their initial study regimen after virologic failure.