Genotypic and phenotypic nevirapine resistance correlates with virological failure during salvage therapy including abacavir and nevirapine.
OBJECTIVE
To study the development of resistance during 8 weeks of salvage therapy with abacavir and nevirapine in combination with other reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs).


METHODS
Samples obtained at baseline and after 8 weeks of therapy from 16 heavily pretreated patients were analysed for genotypic and phenotypic resistance. Genotypic resistance was analysed in cell-associated DNA and plasma HIV-RNA using direct sequencing. Phenotypic resistance was analysed in a PBMC-based assay and in a recombinant virus assay. Plasma viral load was measured at baseline and after 2, 4 and 8 weeks of therapy.


RESULTS
The majority of patients was genotypically and phenotypically resistant to lamivudine, abacavir, zidovudine and PIs, whereas 50% of the patients showed resistance to nevirapine at baseline in at least one of the methods used. After 8 weeks of salvage therapy, no additional development of resistance against nucleoside reverse transcriptase inhibitors and PIs could be detected. However, the amount of patients resistant to nevirapine increased to 83%. When the patients were divided into two groups according to baseline resistance against nevirapine, a significantly higher transient reduction in viral load was observed in patients with nevirapine-sensitive HIV at baseline compared to patients with resistant HIV at baseline.


CONCLUSIONS
The transient effect of salvage therapy including abacavir and nevirapine was due to the effect of nevirapine. The lack of effect of abacavir was most likely due to cross-resistance between abacavir and lamivudine/zidovudine used in previous treatment.
Jørgensen
L B
LB
Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
Katzenstein
T L
TL
Gerstoft
J
J
Mathiesen
L R
LR
Pedersen
C
C
Nielsen
C
C
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000032:analysis; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D019829:Nevirapine / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016879:Salvage Therapy; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015224:Dideoxynucleosides; D019829:Nevirapine; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir