Twenty years following the description of the broad-spectrum
antiviral activity of S-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(
S)-HPMPA] [De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J, Maudgal PC. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986;323:464-7], the acyclic
nucleoside phosphonates have acquired a prominent therapeutic position: (i)
cidofovir in the treatment of
papilloma-, herpes-, adeno- and
poxvirus infections, (ii)
adefovir in the treatment of
chronic hepatitis B virus (HBV)
infections, and (iii)
tenofovir in the treatment of human immunodeficiency virus (
HIV) infections (
AIDS). Although formally approved only for the treatment of human cytomegalovirus (HCMV)
retinitis in
AIDS patients,
cidofovir has been used successfully in the treatment of various other
DNA virus infections, particularly human papilloma virus (HPV)-associated lesions.
Adefovir dipivoxil has become a standard
therapy for HBV
infections, especially when resistant to
lamivudine.
Tenofovir disoproxil fumarate (TDF) is the corner stone of the triple-
drug (TDF,
emtricitabine, and
efavirenz) combination
therapy for
AIDS, and TDF, alone or combined with
emtricitabine may in the future evolve to the standard
therapy of
hepatitis B. Guided by the results obtained with
tenofovir in the prevention of parenteral, intravaginal and perinatal
infections with simian immunodeficiency virus in monkeys, and the safety profile gathered with TDF in humans with
AIDS over the past 5 years since TDF was licensed for clinical use, it should be further pursued for the pre- and post-exposure prophylaxis of
HIV infections in humans. Meanwhile, new classes of both acyclic (i.e. PMPO-DAPy, PMEO-DAPy, HPMPO-DAPy) and cyclic
nucleoside phosphonates (i.e. PMDTA, PMDTT, GS9148) have been accredited with an
antiviral potency and selectivity similar to those of
cidofovir,
adefovir and/or
tenofovir.