Antiviral Resistance of Biologic HIV-2 Clones Obtained From Individuals on Nucleoside Reverse Transcriptase Inhibitor Therapy

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Abstract
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 (IC50), 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. Address correspondence and reprint requests to Albert D. M. E. Osterhaus, Erasmus University Rotterdam, Institute of Virology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Manuscript received November 30, 1999; accepted June 30, 2000. © 2000 Lippincott Williams & Wilkins, Inc.