Characteristics of study participants.

<p>Characteristics of study participants.</p

Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation

<div><p>Introduction</p><p>HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve.</p><p>Methods</p><p>An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations. The DRM pattern-ARV combinations included 52 nucleoside RT inhibitor (NRTI) DRM pattern-ARV combinations (13 patterns x 4 NRTIs), 27 nonnucleoside RT inhibitor (NNRTI) DRM pattern-ARV combinations (9 patterns x 3 NNRTIs), 39 protease inhibitor (PI) DRM pattern-ARV combinations (13 patterns x 3 PIs) and 42 integrase strand transfer inhibitor (INSTI) DRM pattern-ARV combinations (14 patterns x 3 INSTIs).</p><p>Results</p><p>There was universal agreement that a GRT report should include the NRTIs lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir disoproxil fumarate; the NNRTIs efavirenz, etravirine, nevirapine, and rilpivirine; the PIs atazanavir/r, darunavir/r, and lopinavir/r (with “/r” indicating pharmacological boosting with ritonavir or cobicistat); and the INSTIs dolutegravir, elvitegravir, and raltegravir. There was a range of opinion as to whether the NRTIs stavudine and didanosine and the PIs nelfinavir, indinavir/r, saquinavir/r, fosamprenavir/r, and tipranavir/r should be included. The expert panel members provided highly concordant DRM pattern-ARV interpretations with only 6% of NRTI, 6% of NNRTI, 5% of PI, and 3% of INSTI individual expert interpretations differing from the expert panel median by more than one resistance level. The expert panel median differed from the HIVDB 7.0 GRT-IS for 20 (12.5%) of the 160 DRM pattern-ARV combinations including 12 NRTI, two NNRTI, and six INSTI pattern-ARV combinations. Eighteen of these differences were updated in HIVDB 8.1 GRT-IS to reflect the expert panel median. Additionally, HIVDB users are now provided with the option to exclude those ARVs not considered to be universally required.</p><p>Conclusions</p><p>The HIVDB GRT-IS was updated through a collaborative process to reflect changes in HIV drug resistance knowledge, treatment guidelines, and expert opinion. Such a process broadens consensus among experts and identifies areas requiring further study.</p></div

Comparison of the HIVDB version 7.0, expert panel median, and eventual HIVDB version 8.1 levels for the 20 DRM pattern / ARV combinations with a difference between HIVDB version 7.0 and the expert panel median.

<p>Comparison of the HIVDB version 7.0, expert panel median, and eventual HIVDB version 8.1 levels for the 20 DRM pattern / ARV combinations with a difference between HIVDB version 7.0 and the expert panel median.</p

Patterns of predicted relative PI susceptibility profiles for 19,379 viruses in HIVDB with 5,634 distinct PI-Resistance patterns^*.

<p>Patterns of predicted relative PI susceptibility profiles for 19,379 viruses in HIVDB with 5,634 distinct PI-Resistance patterns^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181357#t008fn001" target="_blank">*</a>}.</p

List of antiretroviral (ARV) drugs and their abbreviations by ARV class.

<p>List of antiretroviral (ARV) drugs and their abbreviations by ARV class.</p

In vitro susceptibilities associated with the 13 PI drug resistance mutation patterns.

<p>In vitro susceptibilities associated with the 13 PI drug resistance mutation patterns.</p

Patterns of predicted relative NNRTI susceptibility profiles for 31,484 viruses in HIVDB with 2,347 distinct NNRTI-Resistance patterns^*.

<p>Patterns of predicted relative NNRTI susceptibility profiles for 31,484 viruses in HIVDB with 2,347 distinct NNRTI-Resistance patterns^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181357#t006fn002" target="_blank">*</a>}.</p

In vitro susceptibilities associated with the 13 NRTI drug resistance mutation (DRM) patterns.

<p>In vitro susceptibilities associated with the 13 NRTI drug resistance mutation (DRM) patterns.</p

Expert panel assessments of 14 NRTI-associated drug-resistance mutation (DRM) patterns.

<p>Abbreviations: ABC (abacavir), AZT (zidovudine), TDF (tenofovir), 3FTC (lamivudine and emtricitabine), S (susceptible), P (potential low-level resistance), L (low-level resistance), I (intermediate resistance), H (high-level resistance). The diameter of each circle is proportional to the number of experts at the assigned level shown on the Y-axis. The bold dash is the median of the expert assessments. The vertical lines represent the HIVDB version 7.0 interpretations.</p

Expert panel assessments of 9 NNRTI-associated drug-resistance mutation (DRM) patterns.

<p>Abbreviations: EFV (efavirenz), ETR (etravirine), RPV (riplivirine), S (susceptible), P (potential low-level resistance), L (low-level resistance), I (intermediate resistance), H (high-level resistance). The diameter of each circle is proportional to the number of experts at the assigned level shown on the Y-axis. The bold dash is the median of the expert assessments. The vertical lines represent the HIVDB version 7.0 interpretations.</p