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

Abstract

OBJECTIVES:

To evaluate the safety, immunological outcome and HIV-1 evolution in the reverse transcriptase (RT) in patients with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF).

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 (P<0.001), 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 VL<400 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 VL<10,000 copies/mL (P=0.01).

CONCLUSIONS:

A bridging regimen with TZV+TDF prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication.

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