Persistent antiretroviral activity of nucleoside analogues after prolonged zidovudine and lamivudine therapy as demonstrated by rapid loss of activity after discontinuation.
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.
Eron
Joseph J
JJ
AIDS Clinical Research Unit, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jeron@med.unc.edu
Bartlett
John A
JA
Santana
Jorge L
JL
Bellos
Nicholas C
NC
Johnson
Judy
J
Keller
Amy
A
Kuritzkes
Daniel R
DR
St Clair
Marty H
MH
Johnson
Victoria A
VA
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine