The addition of mycophenolate mofetil to antiretroviral therapy including abacavir is associated with depletion of intracellular deoxyguanosine triphosphate and a decrease in plasma HIV-1 RNA

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 31; no. 1; p. 45
• Main Authors: Margolis, David M, Kewn, Stephen, Coull, Jason J, Ylisastigui, Loyda, Turner, Diana, Wise, Holly, Hossain, Mohammed M, Lanier, E Randall, Shaw, Leslie M, Back, David
• Format: Journal Article
• Language: English
• Published: United States 01.09.2002
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - virology; Anti-HIV Agents - administration & dosage; Apoptosis; CD4 Lymphocyte Count; Deoxyguanine Nucleotides - analysis; Dideoxynucleosides - administration & dosage; Drug Resistance, Viral; Drug Therapy, Combination; HIV-1; Humans; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; RNA, Viral - blood
• ISSN: 1525-4135
• DOI: 10.1097/00126334-200209010-00006

Mycophenolic acid (MPA) enhances the in vitro activity of abacavir (ABC) and other nucleoside analog reverse transcriptase inhibitors (NRTIs) against sensitive and NRTI-resistant HIV-1. This may occur via depletion of intracellular deoxyguanosine triphosphate (dGTP). Mycophenolate mofetil (MMF) 500 mg twice daily was added as a single agent to the antiretroviral regimens of five patients failing maximal available therapy. Therapy included ABC, and in most cases didanosine (DDI) and tenofovir (TDF). At entry, mean plasma HIV-1 RNA (VL) was 5.02 log copies/mL (median 4.78, range 4.71-5.63) and mean CD4 count was 106/microL (median 117, range 11-174). MMF was well tolerated. CD4 cell counts did not change significantly from baseline for up to 60 weeks of follow-up. Three of five subjects had VL declines of >0.5 log copies/mL immediately after adding MMF; a fourth subject had a sustained decline of >0.5 log copies/mL after week 8. Declines of >0.5 log copies/mL were lost in two patients at 6 and 8 weeks, and persisted in two patients at 36 and 60 weeks of follow-up, respectively. An increase in the ratio of carbovir triphosphate (CBV-TP), the active antiviral metabolite of ABC, to dGTP was documented in 3 of 4 subjects in temporal association with decreased VL. Trough plasma MPA levels ranged from 0.26-1.67 microg/mL; peak levels 90 minutes after dosing from 1.20-7.77 microg/mL. AUC of MPA appeared little changed when measured over 28 weeks of therapy. Declines in VL were observed in association with measurable changes in the CBV-TP/dGTP ratio in some patients, whereas MPA AUC was below the 30-60 microg*hr/mL range targeted in organ transplantation. The possibility that MMF may enhance the effect of selected NRTIs and be tolerated in late stage HIV disease deserves careful randomized study.