HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure

Swenson, Luke C.a; Min, Jeong Euna; Woods, Conan K.a; Cai, Erica; Li, Jonathan Z.b; Montaner, Julio S.G.a; Harrigan, P. Richarda; Gonzalez-Serna, Alejandroa

AIDS:
doi: 10.1097/QAD.0000000000000203
Clinical Science
Abstract

Background: The clinical implications of emergent HIV drug resistance on samples with low-level viraemia (LLV <1000 copies/ml) remain unclear. We undertook the present analysis to evaluate the impact of emergent HIV drug resistance at LLV on the risk of subsequent virologic failure.

Methods: One thousand, nine hundred and sixty-five patients had genotype results at LLV. Risk of virologic failure (≥1000 copies/ml) after LLV was evaluated by Kaplan–Meier analysis and Cox proportional hazards regression. Resistance was assessed using the Stanford algorithm or virtual phenotypes. Patients were grouped into four susceptibility categories (’GSS’ or ‘vPSS’) during LLV, corresponding to the number of ‘active’ drugs prescribed: <1; 1–1.5; 2–2.5; and ≥3.

Results: A total of 1702 patients with follow-up on constant therapy were eligible for analysis. Participants excluded due to changing therapy or loss to follow-up before their next observation had mostly similar characteristics to included participants. There was a ‘dose-dependent’ increase in the hazard ratio for virologic failure with susceptibility categories at LLV. Compared with a GSS of at least 3, hazard ratios for virologic failure were 1.4 for GSS 2–2.5; 2.0 for GSS 1–1.5; and 3.0 for GSS less than 1 (P < 0.001). Numerous sensitivity analyses confirmed these findings.

Conclusion: Our results demonstrate that emergent HIV drug resistance at LLV is strongly associated with subsequent virologic failure. Furthermore, we uncovered a ‘dose-dependent’ increase in the hazard ratio for virologic failure with decreasing GSS estimated at the time of LLV. On the basis of these findings, we propose that resistance genotyping be encouraged for HIV-infected individuals on antiretroviral therapy experiencing low-level viraemia.

Author Information

aBC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada

bBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Correspondence to Luke C. Swenson, BC Centre for Excellence in HIV/AIDS, 680-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Tel: +1 604 806 8281; fax: +1 604 806 8464; e-mail: lswenson@cfenet.ubc.ca

Received 28 November, 2013

Revised 6 January, 2014

Accepted 6 January, 2014

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© 2014 Lippincott Williams & Wilkins, Inc.