AEGiS-05CROI: A phase I study of 1592U89 in HIV-infected children.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



A phase I study of 1592U89 in HIV-infected children.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:130 (abstract no. 269)

Kline MW, Blanchard S, Shenep JL, McKinney RE Jr, Van Dyke RB, Culnane M, Dane-Hower S, Lanier ER, Hetherington S; Texas Children's Hospital, Houston, TX.

Objective. To evaluate 1592U89 given alone and in combination with other antiretroviral agents in HIV-infected children. Methods. In step 1, subjects discontinued prior antiretroviral therapy and were given 1592U89, 4 mg/kg BID for six weeks, followed by 8 mg/kg BID for six weeks (cohort 1, n=39); or 8 mg/kg BID for 12 weeks (cohort 2, n=8). In step 2, subjects were randomized to therapy with a second antiretroviral agent (ZDV, d4T, ddI, or 3TC) plus 1592U89 (8 mg/kg BID). Results. The study population had a median age of 6.7 yrs (range, 7 mos-12 yrs). Forty-six of 47 children had a history of antiretroviral therapy (median duration, 3.8 yrs). Thirty-seven of 39 children from cohort 1 completed step 1 and were randomized to step 2. Two children were removed from treatment at step 1 because of toxicity (one case each of drug reaction and peripheral neuropathy). All eight children of cohort 2 completed step 1. Treatment-associated laboratory abnormalities greater than grade 2 were not observed during step 1. In step 2, three children experienced possible treatment-associated neutropenia. There was no change in median CD4+ count or plasma HIV RNA concentration after discontinuing prior therapy and administering 1592U89 monotherapy for six or 12 weeks. Resistance phenotyping of HIV isolates at baseline predicted virologic response to 1592U89; however, genotypic analysis of baseline and week 12 isolates revealed preexisting mutations which may have contributed to the lack of response. Conclusions. Therapy with 1592U89 is associated with excellent short-term tolerance and safety in HIV-infected children. Additional studies are in progress to better define the immunologic and antiviral effects of 1592U89.

Keywords: AEGIS, Dideoxynucleosides, HIV, Stavudine, Zidovudine, CD4 Lymphocyte Count, Anti-HIV Agents, Didanosine, Lamivudine, Reverse Transcriptase Inhibitors, HIV Infections, HIV Protease Inhibitors, HIV-1 Reverse Transcriptase, abacavir, Child, Human, AIDSKWDaegis,dideoxynucleosides,hiv,stavudine,zidovudine,cd4lymphocytecount,anti-hivagents,didanosine,lamivudine,reversetranscriptaseinhibitors,hivinfections,hivproteaseinhibitors,hiv-1reversetranscriptase,abacavir,child,human,aids

1998-02-01
269

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.