Markowitz M, Hu J, Louie M, Barsoum S, Hurley A, Flanigan T, Pierce A, Shaefer M, Nixon D; International Conference on AIDS.
Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. MoPeB2249.
M. Markowitz, Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, United States, Tel.: +1 212 448 5020, Fax: +1 212 327 7299, E-mail: marty@adarc.org
Background: 38 newly HIV-1 infected subjects have received HAART including ABC 300mg, 3TC 300mg and APV 900mg q12h and IND 800mg q8h. After 12 months and an enrollment of 15 subjects, treatment was altered with APV raised to 1200 mg q12h and IND ceased after week 16. On average, symptomatic subjects (92%) were treated within 38 days of symptoms. Mean baseline HIV-1 RNA was 456,678 copies/ml. Mean CD4/CD8 were 554/1264 cells/mm3. All but one individual was infected with virus susceptible to all 4 agents. Methods: Virologic response to therapy is determined by measuring levels of plasma HIV-1 RNA. Immunologic response to therapy is determined measuring T cell subsets, in vitro T cell proliferation to Gag and levels of CTLe using elispot. Results: Sixteen of 22 (73%) subjects who have completed at least 24 weeks of therapy have plasma HIV-1 RNA levels fell below detection (50 copies/ml). The mean immunologic response to therapy at 24 weeks has included these changes: CD4 +370 cell/mm3, CD8 - 463 cells/mm3, S.I. (p24) - 5.3 (11/22 having S.I.>4.95 at week 24). Levels of CTLe vary considerably in each subject and are detectable in all subjects studied (n = 19) at week 24-48. Thirty-two of 38 subjects remain on study and on study drugs for 0.5 to 16 months. Adverse events leading to treatment change included; APV intolerance (n = 2, on ABC/3TC/IND), erythema multiforme (n = 1, off drug/offstudy, resolved), fever and rash (n = 1, resolved with discontinuation of ABC, on Combivir/APV/IND), and Grade 3/4 elevation of LFTs (n = 2, resolved off combination PI therapy, remains on APV), recurrent Grade 3/4 hyperamylasemia (n = 1, off therapy). One patient withdrew consent at day 8. Conclusions: Quadruple therapy as originally designed resulted in poor adherence due to 5 dosing intervals daily. However, once amended, the 16-week induction followed by q12 h triple drug maintenance resulted in subject retention, improved adherence, and an excellent antiviral and immunologic responses.
Publication Types:
Keywords:
- Antiretroviral Therapy, Highly Active
- Clinical Trials as Topic
- Combivir
- Dideoxynucleosides
- HIV-1
- Humans
- In Vitro
- Indinavir
- Lamivudine
- Sulfonamides
- Zidovudine
- abacavir
- amprenavir
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102237849
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