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HIV genotyping approach benefited ART-experienced patients
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Using 454 sequencing improved predictions of virologic outcomes among treatment-experienced patients with HIV compared with Sanger sequencing, according to recent data published in Clinical Infectious Diseases
“Ultrasensitive HIV-1 genotyping helps physicians make more accurate estimates of the residual activity of ART drugs in patients with multidrug-resistant HIV,” Roger Paredes, MD, PhD, of the HIV Unit and irsiCaixa AIDS Research Institute in Badalona, Spain, told Infectious Disease News. “This allows physicians to design more efficacious ART combinations to tackle multidrug HIV resistance.”
Roger Paredes
The retrospective study included 132 patients across four Spanish academic hospitals who initiated salvage ART with either a protease inhibitor boosted with ritonavir (Norvir, AbbVie), raltegravir (Isentress, Merck) or etravirine (Intelence, Janssen). The patients had a viral load of at least 5,000 copies/mL within the 48 weeks preceding the treatment change with at least 1 mL of plasma available for genotypic resistance testing. The researchers used Sanger and 454 sequencing to generate genotypic sensitivity score (GSS) estimates and compared the effectiveness of each at predicting virologic failure.
Of the 132 patients, 28 (21%) experienced virologic failure, defined as two consecutive viral load measurements of 200 copies/mL or more at least 12 weeks after initiating salvage therapy. In a receiver operating characteristic analysis, the 454 sequencing predicted virologic failure better than Sanger sequencing (area under the curve: 0.69 vs. 0.6). Patients with a 454-GSS score of less than 3 had a significantly shorter time to virologic failure compared with those with a score of 3 or more, but there was no significant difference in time to virologic failure according to Sanger-GSS score.
In a multivariate analysis, a 454-GSS score of less than 3 and the number of previous antiretroviral medications received were associated with increased risk for virologic failure.
Paredes said that previous studies have shown that ultrasensitive genotyping is important in treatment-naïve patients, and now this study highlights in importance in treatment-experienced patients receiving salvage therapy.
“These data will further boost the interest of clinicians and diagnostic companies towards finally bringing next-generation sequencing to the HIV clinic,” Paredes said. “Once these tools become available, provided they deliver technically robust data in an easily interpretable manner, most clinicians and clinical labs will turn towards ultrasensitive genotyping for their clinical practice.”
Paredes said that he is now interested in evaluating the clinical value of ultrasensitive genotyping in other settings, such as in patients initiating treatment with novel integrase inhibitors or attachment inhibitors. Also important is finding ways to reduce the cost of sequencing, to allow for global resistance surveillance. — by Emily Shafer
Disclosure: See the study for full list of researchers’ financial disclosures.
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