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Publications (3)8.55 Total impact

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    ABSTRACT: Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from 86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1 RNA > or =1000 copies/ml) and analyzed to examine the association between RT mutations and phenotypic resistance to d4T. Resistance-associated mutations were analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two commercially available methods. Statistically significant increases (p < 0.001) in phenotypic fold resistance to d4T were observed in virus with at least one TAM or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold for the Antivirogram assay and 3-fold for the Phenosense HIV assay, only slightly above the levels used to designate decreased susceptibility to d4T. Subjects can experience viremia on d4T-containing regimens with virus exhibiting only small increases in IC(50), suggesting that relatively small changes in viral susceptibility to d4T may influence drug efficacy.
    AIDS Research and Human Retroviruses 09/2001; 17(12):1107-15. · 2.71 Impact Factor
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    ABSTRACT: This open-label, multicenter, single-arm clinical trial assessed the 48-week efficacy of a twice-daily triple nucleoside reverse-transcriptase inhibitor regimen containing a lamivudine (150 mg)-zidovudine (300 mg) combination tablet (COM) and abacavir (ABC; 300 mg) in 87 antiretroviral therapy-experienced, protease inhibitor-naive patients infected with human immunodeficiency virus type 1 (HIV-1). At baseline, the median plasma HIV-1 RNA level was 3.10 log(10) copies/mL, and the median CD4 cell count was 506 cells/mm(3). An intent-to-treat&rcolon;observed analysis showed that, at weeks 24 and 48 of treatment, HIV-1 RNA level was <400 copies/mL in 48 (76%) of 63 and 45 (82%) of 55 patients, respectively, and <50 copies/mL in 37 (59%) of 63 and 31 (56%) of 55 patients, respectively. Previous zidovudine or lamivudine use and presence at baseline of the M184V reverse-transcriptase mutation did not impact virologic response. Median CD4 cell counts were maintained above baseline throughout the study. COM plus ABC was generally well tolerated.
    The Journal of Infectious Diseases 02/2001; 183(4):571-8. · 5.85 Impact Factor
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    ABSTRACT: The type and frequency of mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase coding region observed in virus from antiretroviral therapy (ART)-experienced, zidovudine (ZDV)-naive subjects receiving stavudine (d4T)-based therapies were compared with mutations observed in virus from ART-experienced subjects with previous ZDV exposure. Plasma HIV-1 RNA was isolated from 67 ART-experienced subjects. Reverse transcriptase mutations were assessed by sequencing polymerase chain reaction products. Thirty-four subjects (51%) were ZDV-experienced (Z(exp)) and 33 (49%) were ZDV-naive and d4T-experienced (d(exp)Z(naive)). Human immunodeficiency virus type 1 from 16 of 33 (48%) d(exp)Z(naive) subjects and from 16 of 34 (47%) Z(exp) subjects had thymidine analog mutations (TAMs). Multi-nucleoside resistance (MNR) mutations were observed in virus from 5 of 33 (15%) d(exp)Z(naive) subjects and 3 of 34 (9%) Z(exp) subjects. At least one TAM or MNR mutation was identified in 18 of 33 (55%) of the former and in 19 of 34 (56%) of the latter group. These results confirm recent reports that TAMs and MNR mutations can arise in subjects receiving d4T-based therapy who are naive with respect to ZDV.
    Journal of human virology 4(4):217-22.