The following links provide information about the ASI and to existing programs that use ASI technology:

Drug resistance algorithms can be specified in an XML document that adheres to an XML Document Type Definition (DTD) that we have developed (and refer to as the ASI2 DTD). The DTD is available online and the text of the DTD is shown in Appendix 1. It provides the basic framework that an algorithm must adhere to.

At the heart of an algorithm is a <DRUG> clause. An example clause taken from the ANRS algorithm is shown below:

<DRUG>
        <NAME>d4T</NAME>
        <FULLNAME>stavudine</FULLNAME>
        <RULE>
            <CONDITION>
                65R OR 151M OR 69i
            </CONDITION>
            <ACTIONS>
    	        <LEVEL>3</LEVEL>
            </ACTIONS>
        </RULE>
</DRUG>

In this example, for the drug d4T the algorithm designer would like the drug to receive a level of 3 if either mutation 151M or 65R is present or if an insertion is present at position 69 (the designer would have previously specified what was meant by level 3 - in ANRS it means "Resistance"). That is, if the condition statement evaluates to true then the appropriate action is taken. Note that the <CONDITION> clause of each <RULE> is free-form text that adheres to a language grammar we have developed for the purpose. This grammar is described in the next section.

The grammar for the ASI2 language is described in the table that follows using BNF notation.

Here is a link to the previous version of the ASI

Some examples of valid clauses in the language follow. The language is very much fairly self-explanatory given that it reads similarly to an English sentence.

1. 151M OR 69i
2. SELECT ATLEAST 2 FROM (41L, 67N, 70R, 210W, 215FY, 219QE)
3. SELECT ATLEAST 2 AND NOTMORETHAN 2 FROM (41L, 67N, 70R, 210W, 215FY, 219QE)
   What this really means is "choose exactly two from the following list". The keyword "EXACTLY", which has not been added to the language yet, would allow that rule to be expressed more compactly.
4. 215FY AND NOT 184VI
   For this to be true, a mutation F or Y must be present at position 215 and a V or I mutation must not be present at position 184.
5. SCORE FROM (65R => 20, 74V => 20, 184VI => 20)
   Scores are added for each score that is triggered by a matching mutation, so if 65R and 74V were present the total score would be 40. A <SCORERANGE> section of the <ACTIONS> would indicate how scores were to be mapped to resistance levels.
6. 151M AND EXCLUDE 69i
   The mutation 69i must not be present for this clause to evaluate to true. That is, 151M would have to be present along with an arbitrary number of other mutations as long as one was not 69i.
7. 69(NOT TDN)
   A mutation at position 69 other than T69D and T69N. The consensus must also be excluded to pick up atypical mutations at this position.
8. 215F OR 215Y
   A long way of saying 215FY.
9. MAX ( 101P => 40, 101E => 30, 101HN => 15, 101Q => 5 )
   Use the maximum score in position 101 among scores triggered by a matching mutation: 40(P), 30(E), 15(H), 15(N), 5(Q)
10. (184V AND 115F) => 20
    a mutation V at position 184 and mutation F at 115 must both be present for the score of 20 to be triggered

Similarly to the previos version, once specified in the ASI2 format, an algorithm can be compiled into an executable set of routines. These routines accept as input a set of mutations and produce as output a list of drug resistance levels along with other output (such as comment strings) as directed by the algorithm. As mentioned in the introduction, SableCC (a Java compiler compiler) was used to create a Java framework; the previous one was written in Perl.

1. Delete processing directives since they are no longer used. Processing directives look like the example below

   <PROCESSING_DIRECTIVES> <RESTRICTED_POSITION_SCORING/> </PROCESSING_DIRECTIVES>



2. Use the new MAX keyword to define the set of mutations among which to choose the highest score since the RESTRICTED_POSITION_SCORING processing directive is no longer used.
   For example, the old ASI (ASI_OLD) rule needs to be rewritten as shown below (ASI2)
   

   A) ASI_OLD <CONDITION>SCORE FROM ( 98G => 10, 100I => 40, 101P => 40, 101E => 30, 101HN => 15, 101Q => 5 ) </CONDITION> B) ASI2 <CONDITION>SCORE FROM ( 98G => 10, 100I => 40, MAX (101P => 40, 101E => 30, 101HN => 15, 101Q => 5) ) </CONDITION>

   In this example, if a mutation list with just 101HP was submitted to the new ASI engine along with:
   A) the original unchanged ASI_OLD rule, the mutation would score a 55 - the sum of both scores, 40 (101P) and 15 (101H); B) the rewritten ASI2 rule, the mutation would score a 40 - the higher of 40 and 15
   


3. Add gene information to link the drug class to a gene. The examples below link the protease and RT genes to their respective drug classes.

   <GENE_DEFINITION> <NAME>PR</NAME> <DRUGCLASSLIST>PI</DRUGCLASSLIST> </GENE_DEFINITION> <GENE_DEFINITION> <NAME>RT</NAME> <DRUGCLASSLIST>NNRTI, NRTI</DRUGCLASSLIST> </GENE_DEFINITION>



4. You must rewrite your scoring ranges if your definitions overlap, since it is no longer allowed. For example, the global range in the old ASI rule (ASI_OLD) had to be rewritten as shown below (ASI2)

   ASI_OLD <GLOBALRANGE> (-INF TO 10 => 1, 10 TO 15 => 2, 15 TO 30 => 3, 30 TO 60 => 4, 60 TO INF => 5) </GLOBALRANGE>

   ASI2 <GLOBALRANGE> (-INF TO 9 => 1, 10 TO 14 => 2, 15 TO 29 => 3, 30 TO 59 => 4, 60 TO INF => 5) </GLOBALRANGE>

1. Hirsch MS, Brun-Vezinet F, D'Aquila RT, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel. JAMA 2000;283:2417-2426.
2. British HIV Association. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med 2001;2(4):276-313.
3. EuroGuidelines Group for HIV Resistance. Clinical and laboratory guidelines for the use of HIV-1 drug resistance testing as part of treatment management: recommendations for the European setting. AIDS 2001;15:309-320.
4. US Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection A. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (The living document, February 4, 2002), http://www.aidsinfo.nih.gov/guidelines/, 2002.