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HIV Med. 2014 Apr;15(4):224-32. doi: 10.1111/hiv.12107. Epub 2013 Nov 12.

Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions.

Author information

1
HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Department of Community Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.

Abstract

OBJECTIVES:

Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first-line ritonavir-boosted, protease-inhibitor (PI/r)-containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir-boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r.

METHODS:

In a retrospective assessment of HIV-infected patients initiating ATV/r-containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation.

RESULTS:

A total of 202 patients [median age 33 years (interquartile range (IQR) 29-40 years); 52% female; median CD4 count 184 cells/μL (IQR 107-280 cells/μL); median HIV RNA 4.6 log10 HIV-1 RNA copies/mL (IQR 3.2-5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10-52) weeks on ART, with a median (IQR) UTrI duration of 10 (3-31) weeks. Fifty-four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3-9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3-4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re-suppressed on ATV/r reinitiation.

CONCLUSIONS:

In this PI-treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r-treated patients prior to ART reinitiation after UTrI.

KEYWORDS:

genotypic resistance; protease inhibitor mutations; unscheduled treatment interruptions; viral supression

PMID:
24215370
DOI:
10.1111/hiv.12107
[Indexed for MEDLINE]
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