This article describes several approaches to a selective
therapy of
virus infections:
(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU [
brivudin]) for the
therapy of herpes simplex virus type 1 and varicella-zoster virus
infections: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (
HPMPC [
cidofovir]) for the
therapy of various DNA virus (i.e., herpesvirus, adenovirus, papillomavirus, polyomavirus, and
poxvirus) infections;
9-(2-phosphonylmethoxyethyl)adenine (PMEA [
adefovir]) for the
therapy of retrovirus, hepadnavirus, and
herpesvirus infections;
(R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for the
therapy and prophylaxis of retrovirus and hepadnavirus
infections; and nonnucleoside
reverse transcriptase inhibitors (NNRTIs), such as tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(IH)-one and -
thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)
thymine (HEPT),
alpha-anilinophenylacetamide (
alpha-APA), and 2',5'bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxat hiole- 2",2"-dioxide)
pyrimidine (TSAO) derivatives, and thiocarboxanilides for the treatment of human immunodeficiency virus type 1 (HIV-1)
infections. For the clinical use of NNRTIs, some guidelines have been elaborated, such as starting treatment with combinations of different compounds at sufficiently high concentrations to effect a pronounced and sustained suppression of the virus. Despite the diversity of the compounds described here and the different viruses at which they are targeted, they have a number of characteristics in common. As they interact with specific
viral proteins, the compounds achieve a selective inhibition of the replication of the virus, which, in turn, should be able to develop resistance to the compounds. However, as has been established for the NNRTIs, the problem of viral resistance may be overcome if the compounds are used from the start at sufficiently high doses, which could be reduced if different compounds are combined. For
HIV infections,
drug treatment regimens should be aimed at reducing the viral load to such an extent that the risk for progression to
AIDS will be minimized, if not avoided entirely. This may result in a real "cure" of the disease but not necessarily of the
virus infection, and in this sense, HIV disease may be reduced to a dormant
infection, reminiscent of the latent
herpesvirus infections. Should virus replication resume after a certain time, the armamentarium of effective anti-HIV and anti-herpesvirus compounds now available, if applied at the appropriate dosage regimens, should make the virus return to its dormant state before it has any chance to damage the host. It is unlikely that this strategy would eradicate the virus and thus "cure" the
viral infection, but it definitely qualifies as a cure of the disease.