Interruption of treatment with individual therapeutic drug classes in adults with multidrug-resistant HIV-1 infection.
BACKGROUND
Many antiretroviral-treated human immunodeficiency virus (HIV)-infected patients experience sustained immunologic and virologic benefit despite the presence of multidrug-resistant HIV. We hypothesized that the use of simplified regimens could maintain treatment benefit while preventing viral evolution and reducing drug-related toxicity and costs.


METHODS
We conducted a 48-week nonrandomized study of adults with multidrug-resistant HIV type 1 infection. Subjects interrupted protease inhibitor (PI) (n=18), reverse-transcriptase inhibitor (RTI) (n=6), or nonnucleoside RTI (NNRTI) (n=6) treatment.


RESULTS
At study entry, subjects had a median reduction in HIV RNA levels of 1.2 log10 copies/mL relative to pretreatment levels. Interruption of PI treatment was associated with stable HIV RNA levels (mean change per week, +0.005 log10 copies/mL; P=.36). PI mutations waned and replicative capacity and HIV RNA levels increased after long-term observation. HIV RNA levels also remained stable in subjects interrupting NNRTI treatment. In contrast, all subjects who interrupted RTI treatment exhibited immediate increases in HIV RNA levels, and most exhibited a subsequent loss of the M184V mutation.


CONCLUSIONS
These data indicate that nucleoside analogues often exert continued antiviral activity in the setting of drug-resistance mutations and that both nucleoside analogues and PIs can select for drug-resistance mutations that reduce viral fitness. These observations support the evaluation of treatment strategies aimed at maintaining the treatment benefit of therapy while reducing drug exposure.
Deeks
Steven G
SG
University of California, San Francisco, and San Francisco General Hospital, San Francisco 94110, USA. sdeeks@php.ucsf.edu
Hoh
Rebecca
R
Neilands
Torsten B
TB
Liegler
Teri
T
Aweeka
Francesca
F
Petropoulos
Christos J
CJ
Grant
Robert M
RM
Martin
Jeffrey N
JN
D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment
D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors