Persistence of drug-resistant HIV-1 after a structured treatment interruption and its impact on treatment response.
OBJECTIVE
Among treated patients with drug-resistant viremia, structured treatment interruptions often result in the re-emergence of drug-susceptible HIV-1. Theoretically, this may allow for a more durable response to salvage therapy. We therefore studied the long-term treatment outcome to antiretroviral therapy in a cohort of patients who had previously interrupted therapy, focusing on the determinants of treatment success versus failure.


METHODS
A prospective observational study of the response to antiretroviral therapy in patients resuming therapy after a treatment interruption. Virological and immunological studies were performed every month for 3 months and then every 3 months.


RESULTS
Twenty-four patients underwent a structured treatment interruption and resumed therapy after a variable period of time (median 20 weeks). The median duration of treatment after the treatment interruption was 109 weeks. A transient virological response was observed in all patients who resumed a regimen containing no drug to which their pre-interruption virus was fully susceptible. Virus isolated during virological failure was genotypically and phenotypically identical to the pre-interruption virus, exhibited reduced replicative capacity, and replicated at levels similar to the pre-interruption baseline. In contrast, durable viral suppression (< 200 copies/ml) was observed in patients who initiated a regimen containing only one drug to which their pre-interruption virus was fully susceptible. Despite viral suppression, the pre-interruption drug-resistant virus population remained detectable in two patients.


CONCLUSIONS
Although drug-resistant HIV-1 persists at low levels during and after the interruption of therapy, durable suppression of this virus population may be achieved with a combination regimen containing only one fully active agent.
Deeks
Steven G
SG
University of California-San Francisco and San Francisco General Hospital, 995 Potrero Avenue, San Francisco, CA 94110, USA. sdeeks@php.ucsf.edu
Grant
Robert M
RM
Wrin
Terri
T
Paxinos
Ellen E
EE
Liegler
Teri
T
Hoh
Rebecca
R
Martin
Jeff N
JN
Petropoulos
Christos J
CJ
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy; D017211:Treatment Failure; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D012367:RNA, Viral