Persistent Antiretroviral Activity of Nucleoside Analogues After Prolonged Zidovudine and Lamivudine Therapy as Demonstrated by Rapid Loss of Activity After Discontinuation

Eron, Joseph J. Jr. MD*; Bartlett, John A. MD†; Santana, Jorge L. MD‡; Bellos, Nicholas C. MD§; Johnson, Judy MSN; Keller, Amy BS; Kuritzkes, Daniel R. MD¶; St. Clair, Marty H. PhD; Johnson, Victoria A. MD#

JAIDS Journal of Acquired Immune Deficiency Syndromes:
Clinical Science
Abstract

Antiretroviral (ARV) treatment decisions are difficult for HIV-1-infected patients on complex treatment regimens who have partial suppression of HIV-1 replication and limited treatment options. Information on the ARV activity of the components of a complex regimen would be useful. Sixteen subjects who had received prolonged therapy with zidovudine (ZDV) and lamivudine (3TC), with a median duration of 32.5 months, were discontinuing this dual-nucleoside regimen and volunteered to have plasma HIV-1 RNA levels monitored over the 2 weeks after discontinuation. All subjects experienced an increase in HIV-1 RNA after discontinuation, with a median increase of 0.54 log10 copies/mL over 2 weeks (range: 0.31-1.71; P < 0.001). An inverse correlation existed between the decline in HIV-1 RNA levels over 2 to 3 years on nucleoside analogue therapy and the increase over the 10 to 14 days off therapy (Spearman r = −0.53; P = 0.036). Over the 2-week period, a subset of individuals who had genotype testing at multiple reverse transcriptase codons associated with ZDV and 3TC resistance had no changes in genotype off therapy. Nucleoside analogue reverse transcriptase inhibitors may have continued ARV activity despite long durations of partially suppressive therapy and the presence of resistant HIV-1.

Author Information

From the *AIDS Clinical Research Unit, University of North Carolina at Chapel Hill, Chapel Hill, NC; †Center for AIDS Research, Duke University, Durham, NC; ‡San Juan AIDS Project, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico; §Southwest Infectious Disease Associates of Dallas, Dallas, TX; Infectious Disease Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC; ¶Section of Retroviral Therapeutics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and #Birmingham Veteran's Affairs Medical Center and Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, AL.

Received for publication March 29, 2004; accepted July 7, 2004.

Reprints: Joseph J. Eron Jr., AIDS Clinical Research Unit, University of North Carolina at Chapel Hill, 211A West Cameron Avenue, Chapel Hill, NC (e-mail: jeron@med.unc.edu).

Supported by GlaxoSmithKline, RR00046, AI50410, and AI40876.

© 2004 Lippincott Williams & Wilkins, Inc.