Antiviral resistance of biologic HIV-2 clones obtained from individuals on nucleoside reverse transcriptase inhibitor therapy.
OBJECTIVE
To study phenotypic and genotypic resistance of HIV-2 against nucleoside reverse transcriptase inhibitors (NRTI).


METHODS
Biologic HIV-2 clones were generated from 3 patients before and after initiation of antiretroviral therapy with zidovudine (AZT) in patient RH2-7, AZT and didanosine (ddI) in patient PH2-1, and after addition of lamivudine (3TC) to AZT monotherapy in patient RH2-5. The sensitivity to NRTI of the virus clones, as defined by the 50% inhibitory concentration (IC(50)), was determined in vitro. The predicted amino acid sequences of the reverse transcriptase proteins from these clones were determined.


RESULTS
Comparing the sensitivity of the biologic HIV-2 clones obtained after start of therapy with those from antiviral naive patients, resistance had developed to AZT (patients RH2-7 and RH2-5) and 3TC (patient PH2-1 and RH2-5). No resistance to AZT was observed in the biologic clone from PH2-1 obtained after start of therapy. The resistant clones from RH2-5 and PH2-1, but not RH2-7, contained amino acid mutations at positions where HIV-1 has been shown to mutate after AZT and 3TC treatment.


CONCLUSIONS
Phenotypic resistance of HIV-2 to nucleoside analogues, which developed in HIV-2-infected patients treated with NRTIs, was associated with genotypic changes. Some of the mutations at amino acid positions in the HIV-2 reverse transcriptase gene corresponded with those involved in HIV-1 resistance, although no conventional mutations associated with resistance to AZT were observed.
van der Ende
M E
ME
Department of Internal Medicine, University Hospital Centre Rotterdam, Rotterdam, The Netherlands.
Guillon
C
C
Boers
P H
PH
Ly
T D
TD
Gruters
R A
RA
Osterhaus
A D
AD
Schutten
M
M
D000328:Adult; D000595:Amino Acid Sequence; D016384:Consensus Sequence; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine