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Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study.

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Methods: Pilot analysis of highly experienced patients (n=28), with > or =1 thymidine-associated mutation (TAM) and the M184V mutation.

Results: Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/microL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (P0.001), with 35.7% (10/28) achieving a VL of 50 copies/mL. The median 24-week decrease in CD4 was -53 cells/microL and only-17 cells/microL when baseline CD4 was 350 cells/microL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VL400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL10,000 copies/mL (P=0.01).

Conclusion: Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/microL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (P0.001), with 35.7% (10/28) achieving a VL of 50 copies/mL. The median 24-week decrease in CD4 was -53 cells/microL and only-17 cells/microL when baseline CD4 was 350 cells/microL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VL400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL10,000 copies/mL (P=0.01).

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