Journal Article

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

Hiroyu Hatano, Peter Hunt, Jodi Weidler, Eoin Coakley, Rebecca Hoh, Teri Liegler, Jeffrey N. Martin and Steven G. Deeks

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 43, issue 10, pages 1329-1336
Published in print November 2006 | ISSN: 1058-4838
Published online November 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/508655
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

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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 ⩾120 days, a plasma HIV RNA load of >500 copies/mL, and ⩾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.

Journal Article.  4551 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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