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Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase inhibitors does not necessarily imply that the subsequent combined use of the drugs will fail. Some HIV strains resistant to one polymerase inhibitor show increased susceptibility to another polymerase inhibitor. After failure of sequential lamivudine and adefovir monotherapy, two patients with hepatitis B changed to treatment with lamivudine plus adefovir and had renewed suppression of HBV. To study the mutational history of resistant HBV subpopulations in the two patients, a part of the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the presence of mutations, in sequential plasma samples. In both patients serial monotherapy caused the replacement in all HBV clones of wild-type virus by classical lamivudine resistant mutants (L180M and M204V/I), which were replaced subsequently by adefovir resistant mutants (A181V and N236T). When finally lamivudine was added to adefovir, the A181V adefovir mutation persisted in all clones and lamivudine-related mutations did not reappear. During 18 months of combination therapy, HBV-DNA levels decreased 10,000, respectively, 1,000-fold, despite the earlier resistance to lamivudine and adefovir. Although clinically insufficient, this effect indicates that HBV polymerase resistance mutations may be antagonistic, which is relevant if chronic HBV infection is to be treated by a combination of polymerase inhibitors.

The second-generation enzyme immunoassays (EIAs) for antibodies against human immunodeficiency virus (HIV) from three manufacturers (Abbott, Organon, Wellcome) and three anti-HIV confirmatory tests, i.e. Western Blot (WB, Biotech, Dupont), radioimmunoprecipitation assay (RIPA, CLB) and a competitive immunoassay (CIA, Abbott) were evaluated on a panel of 6,488 serum samples, which had previously been used for the comparison of seven first-generation EIAs. For the present study the panel was expanded with sequential serum samples from 12 individuals followed at 1- to 3-month intervals during seroconversion for anti-HIV. The second-generation EIAs and confirmatory tests were significantly more sensitive than the first-generation EIAs as was demonstrated by detection of 10- to 100-fold higher endpoint titers in anti-HIV-positive sera as well as by earlier detection of anti-HIV in 7-11 of the 12 subjects, who seroconverted. In all sera obtained during early HIV infection anti-gp 160/120env antibodies (WB, CIA) were found in addition to anti-p24 (WB, RIPA) and in serial twofold dilutions of these 'seroconversion samples' the new Abbott EIA and RIPA were significantly more sensitive than WB (p less than 0.05), whereas CIA and the new Organon EIA were significantly less sensitive than WB (p less than 0.05). The new Wellcome EIA was not statistically less sensitive than WB. The CIA was as sensitive as WB for antibodies to envelope proteins (gp41, gp160, gp120), but considerably less sensitive for core (p24) antibodies, as was shown in sera obtained during early as well as later clinical stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)