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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
Author(s) -
Llibre JM,
Bonjoch A,
Iribarren J,
Galindo MJ,
Negredo E,
Domingo P,
PérezAlvarez N,
MartinezPicado J,
Schapiro J,
Clotet B
Publication year - 2008
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2008.00581.x
Subject(s) - abacavir , medicine , lamivudine , zidovudine , resistance mutation , virology , reverse transcriptase , reverse transcriptase inhibitor , viral load , lentivirus , virus , viral disease , polymerase chain reaction , antiretroviral therapy , biology , hepatitis b virus , biochemistry , gene
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 ≥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/μL. 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/μL and only −17 cells/μL when baseline CD4 was <350 cells/μL. 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), ≥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.