A Randomized Trial of Simplified Maintenance Therapy with Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection

Abstract

This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n=79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine (n=84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P=.081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P=.021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.

A prospective, 96‐week study of the impact of Trizivir®, Combivir®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

“…In this study, the TZV regimen was well tolerated over 96 weeks and the safety profile did not change over time. Thus, the incidence of adverse events in the TZV group at 96 weeks was comparable to that reported in other studies that have evaluated ABC/3TC/ZDV over 48 weeks [13,14]. The greater elevation of serum lactate in the d4T/3TC/NFV group is consistent with earlier studies showing d4T to be associated with most NRTI-related cases of hyperlactataemia, which may be related to the greater mitochondrial toxicity profile of this thymidine compared to other NRTIs [30].…”

“…In patients whose baseline viral load was o100 000 copies/mL, the proportion with HIV-1 RNA o50 copies/mL at week 96 was 39% (27 of 70) with TZV, 38% (26 of 69) with COM/NFV, and 34% (23 of 67) with d4T/3TC/NFV. The proportion of patients with baseline HIV-1 RNA levels4100 000 and o200 000 copies/ mL who achieved HIV-1 RNA o50 copies/mL at week 96 was greater in the TZV group than in the d4T/3TC/NFV or COM/NFV group [53% (eight of 15) versus 29% (four of 14) and 42% (eight of 19), respectively; Fig. 4c].…”

Characteristics, Determinants, and Clinical Relevance of CD4 T Cell Recovery to <500 Cells/ L in HIV Type 1--Infected Individuals Receiving Potent Antiretroviral Therapy

“…As a consequence, a substantial proportion of treated individuals show incomplete or even poor CD4 T cell recovery [6,14]. In some studies, CD4 T cell counts seemed to reach a plateau after the first 2-3 years of ART [7,15,16], whereas other studies found that, for selected groups of patients with a well-suppressed HIV-1 RNA load, there were continuous, albeit small increases in CD4 T cell counts even after 3-4 years of ART [11,17]. Thus, long-term CD4 T cell recovery, including its modulating factors, needs further evaluation.…”

Changing Patterns in the Selection of Viral Mutations among Patients Receiving Nucleoside and Nucleotide Drug Combinations Directed against Human Immunodeficiency Virus Type 1 Reverse Transcriptase

“…In contrast, the 3TC and ABC combination and the 3TC and TDF combination seem to be effective NRTI backbones when they are used together with an NNRTI or a PI. Triple-NRTI regimens containing ZDV continue to play an important role in ART as an alternative to PI-and NNRTI-containing regimens as initial therapy, as simplified therapy, and in some quadruple regimens (5,21,25,29 ). Several studies have suggested that the triple combination of ZDV, ABC, and 3TC is less potent than two NRTIs plus either a PI or an NNRTI (12,25,29).…”