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Updated draft:  HIV-1 Drug Resistance Mutations (DRMs) for Point of Care (POC) Testing (Stable read-only November 20).
https://drive.google.com/folderview?id=0B1dACJ3Ko969ZElRNk9EaGhMYUk&usp=sharing

Options for providing feedback:  1. Add comments to a shared text box  2. Edit the editable version of this document. 3. Download draft and then upload it to this folder or email it to me rshafer@stanford.edu.

Bob,
We spoke this week.  

One suggestion moving forward is to have a literature review on the data on clinical significance of the major mutations for Tier 1 (to begin with), specially for M184V (if you'd poll a group of clinicians and resistant experts you'd probably get a divided group) and to grade the data. This issue keeps getting discussed.  Aside from M184V is to look at the few papers that show K103N mutation and that in some patients, they can resuppress.  U Was, Lisa's data presented yesterday had a couple of these patients as well. 

Second suggestion is to open up the database to get more info on current first line regimen so we get more TDF containing regimen in the analysis.

Arlene

Watching Bob Shafer presentation on point of care (POC) selection of drug resistance mutation in Cape Town, South Africa. Excellent to see Stanford HIVDB interest in working with affordable technologies for resource limited countries.

I read the draft manuscript and think that it is very good. I suggest to determine the level of nucleotide variation around the mutations selected as Tier 1 for NRTI, NNRTI and PI. The rational for that is because probes for POC need to be designed to take in account the variation around the mutations. These analyses could be presented as supplementary information.

Thanks Bob:
It will be difficult to predict the future of point mutation assays (see i.e. scenario # 2 and tier 1 POC DRMs). The main question here is which mutation to test for?
For example 5-10% of patients receiving non-tenofovir-based therapy select the K65R mutation in treatment program in LMICs.
Cheers

References 
1. Chung MH, Beck IA, Dross S, Tapia K, Kiarie JN, Richardson BA, Overbaugh J, Sakr SR, John-Stewart GC, Frenkel LM. Oligonucleotide Ligation Assay Detects HIV  Drug Resistance Associated with Virologic Failure among Antiretroviral-Naïve Adults in Kenya. J Acquir Immune Defic Syndr. 2014 Aug 21. [Epub ahead of print] PubMed PMID: 25140907.
2.Sungkanuparph S, Manosuthi W, Kiertiburanakul S, Saekang N, Pairoj W, Chantratita W. Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. J Clin Virol. 2008 Apr;41(4):310-3. doi:10.1016/j.jcv.2007.12.015. Epub 2008 Mar 7. PubMed PMID: 18316243.

Hi Bob,

Responding to Ravi's email through this forum.  Agree that we should also have a statement on adherence counseling and how POC GRT could be placed (probably after 2nd detectable VL) . And note the importance of adherence intervention at first detectable viral load
 (Using current WHO algorithm)

Cheers,
Arlene

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HIV-1 Drug Resistance Mutations (DRMs) for Point of Care (POC) Testing (Stable read-only August 18, 2014 draft)

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HIV-1 Drug Resistance Mutations (DRMs) for Point of Care (POC) Testing (An editable document based on the August 18, 2014 draft)
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