Twice‐Daily Triple Nucleoside Intensification Treatment with Lamivudine‐Zidovudine plus Abacavir Sustains Suppression of Human Immunodeficiency Virus Type 1: Results of the TARGET Study

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.

Response to Lamivudine-Zidovudine plus Abacavir Twice Daily in Antiretroviral-Naive, Incarcerated Patients with HIV Infection Taking Directly Observed Treatment

“…Our study also showed that HIV-1 RNA undetectability was more likely to be achieved in antiretroviral-naive patients with baseline HIV-1 RNA levels of !100,000 copies/mL than it was in patients with baseline levels of у100,000 copies/mL (76% vs. 40% at week 24, determined by use of the 50-copy/mL assay); similar findings in association with COM-abacavir have been reported elsewhere [7]. These results may be because patients with lower pretreatment HIV-1 RNA levels potentially have better immunological function [11].…”

“…In NZTA4006, Thompson et al [19] previously found that interruptions in abacavir dosing are not associated with an increased risk of hypersensitivity reaction. The apparent lack of clinically significant effects of COM-abacavir on serum levels of lipids and glucose seen in this study is noteworthy because it has likewise been observed in other clinical trials of this triple-nucleoside combination, which have had durations of up to 48 weeks [4,7]. Several teams of investigators have found that, when twicedaily doses of COM-abacavir are substituted for HAART regimens because patients have had hyperlipidemia and hyperglycemia, it can result in reversion of these abnormalities [20][21][22].…”

“…One compact HAART regimen that has proven to be effective in the suppression of the plasma HIV type 1 (HIV-1) RNA of HIV-infected persons consists of 3 nucleoside reverse-transcriptase inhibitors (NRTIs) administered twice per day as a single lamivudine-zidovudine combination tablet (COM; 150 mg/300 mg) and a single 300-mg abacavir tablet (total dosage, 4 tablets per day) [3][4][5][6][7]. Unlike protease inhibitors and non-NRTIs (NNRTIs), COM-abacavir can be administered without water or dietary restrictions and, generally, without concern for overlapping toxicities of each component, clinically relevant cross-resistance, or possible drug interactions.…”

Zidovudine, Lamivudine, and Abacavir Have Different Effects on Resting Cells Infected with Human Immunodeficiency Virus In Vitro

“…ABC is phosphorylated by a novel enzymatic pathway (15) which might contribute to its activity in resting cells. In the initial clinical trials, ABC appeared more potent than other nucleoside analogs (33,40), and subsequent clinical experience corroborates the earlier data (22,25,28). Whether this in vivo activity is related to its activity in resting (or latently infected) cells is an intriguing possibility which will require additional studies.…”

Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir

“…Although the triple NRTI regimen was inferior to efavirenz-containing arms, it did suppress HIV-1 RNA to <50 copies/mL in 61% of patients at week 48. Similarly, TARGET [19], a single-arm trial of twice-daily 3TC/AZT/ABC, showed HIV-1 RNA suppression to <50 copies/mL in 56% of patients. Finally, NZTA4007 [20], a single-arm trial of 3TC/AZT/ABC, achieved HIV-1 RNA suppression to <50 copies/mL in 75% of patients at 24 weeks.…”