Rate of viral evolution and risk of losing future drug options in heavily pretreated, HIV-infected patients who continue to receive a stable, partially suppressive treatment regimen.
BACKGROUND
Many treatment-experienced, HIV-infected patients who have limited therapeutic options for complete viral suppression continue to receive a partially suppressive treatment regimen pending the availability of at least 2 new antiretroviral drugs. The major risk of this approach is ongoing viral evolution and the loss of future drug options.


METHODS
Antiretroviral-treated subjects with incomplete viral suppression were sampled from a clinic-based cohort. Inclusion criteria were receipt of a stable treatment regimen for > or = 120 days, a plasma HIV RNA load of > 500 copies/mL, and > or = 1 resistance mutation. Phenotypic and genotypic resistance testing was performed every 4 months.


RESULTS
The 106 patients who were eligible for the study had a median of 3 observations during a median of 11.3 months. An estimated 23% and 18% developed at least 1 new nucleoside analogue and 1 new protease inhibitor mutation at 1 year, respectively. An estimated 30% lost the phenotypic equivalent of 1 susceptible drug at 1 year. A lower number of total mutations at baseline was a significant predictor of developing a new nucleoside analogue mutation (P=.01). At 1 year, the probability that an existing mutation would become undetectable using population-based sequencing was 32%. There was a higher rate of change at nonresistance codons than at codons known to be associated with drug resistance.


CONCLUSIONS
Heavily pretreated patients with HIV infection who remain on a partially suppressive regimen have a measurable risk of losing future drug options, particularly those patients who have few baseline mutations. Resistance mutations vary over time, which suggests that the results of any single resistance test may not be representative of all mutations selected by a given treatment regimen.
Hatano
Hiroyu
H
University of California San Francisco, San Francisco, CA, USA.
Hunt
Peter
P
Weidler
Jodi
J
Coakley
Eoin
E
Hoh
Rebecca
R
Liegler
Teri
T
Martin
Jeffrey N
JN
Deeks
Steven G
SG
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D005075:Biological Evolution; D024921:Drug Resistance, Multiple, Viral; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans
D019380:Anti-HIV Agents