The use of β-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection

David M. Margolis, A. Lisa Mukherjee, Courtney V. Fletcher, Evelyn Hogg, Debra Ogata-Arakaki, Tianna Petersen, David Rusin, Ana Martinez, John W. Mellors

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

OBJECTIVE: We evaluated the safety, tolerability and antiretroviral activity of β-D-2,6-diaminopurine dioxolane (DAPD; amdoxovir) with or without mycophenolate mofetil (MMF) in HIV-1 infection following extensive antiretroviral therapy (ART). METHODS: Oral DAPD 500 mg twice daily with placebo or MMF 500 mg twice daily was added to failing ART. HIV-1 RNA viral load (VL) decline to week 2 was analyzed by intent-to-treat, using rank-based tests. Patients with VL decline > 0.5 log10 copies/ml at week 2 (virologic response, VR) optimized ART and continued therapy for up to 96 weeks. RESULTS: Forty adults with median VL 4.5 log10 copies/ml, median 184 CD4+ cells/μl, and a median of 6 nucleoside reverse transcriptase inhibitor (NRTI) mutations (range, 1-8) were randomized. Median VL reduction at week 2 was -0.26 log10 copies/ml (P < 0.0001). Response to DAPD/placebo (median -0.37 log10 copies/ml) was unexpectedly greater than to DAPD/MMF (median -0.23 log10 copies/ml), although this difference was not statistically significant (P = 0.59). MMF appeared to lower concentrations of DAPD and its metabolite dioxolane guanosine. Of 10 patients with VR (DAPD 7, DAPD/MMF 3), four persisted beyond week 24. VR was more frequent with ≤ 5 baseline NRTI mutations (P = 0.12) or < 4 thymidine-associated mutations (TAMs) without E44D or V118I (P = 0.08). Twenty-three patients received extended DAPD +/- MMF; five beyond week 24. Few adverse events were related to study medications. CONCLUSIONS: The addition of DAPD +/- MMF to failing therapy appears safe and well tolerated. DAPD had significant activity at week 2 (mean -0.35 log10) in heavily pretreated patients that was not augmented by MMF.

Original languageEnglish (US)
Pages (from-to)2025-2032
Number of pages8
JournalAIDS
Volume21
Issue number15
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Margolis, D. M., Mukherjee, A. L., Fletcher, C. V., Hogg, E., Ogata-Arakaki, D., Petersen, T., Rusin, D., Martinez, A., & Mellors, J. W. (2007). The use of β-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection. AIDS, 21(15), 2025-2032. https://doi.org/10.1097/QAD.0b013e3282364381