Summary of resistance studies at Retrovirus

3 April 2004. Related: Conference reports, Drug resistance, CROI 11 (Retrovirus) 2004.

Simon Collins, HIV i-Base

Many of the oral presentations provided a higher profile for research than was first presented at the XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, held in June 2003.

These studies, based on the same data are reported in our report from that meeting in September/August 2003 issue of HTB.

http://www.i-base.org.uk/pub/htb/v4/htb4-7/index.html

Summary conclusions from these important studies included:

• the persistence of transmitted drug resistance including 9/11 patients including no PI-reversion to wild-type after more than three years. [1] Similar duration of transmitted resistance was also reported by a UK group in a new study at the meeting. [2]
• that efavirenz-exposure correlated more strongly with treatment failure than the absence of evidence of genotypic NNRTI-resistance and that most currently available resistance assays are insufficiently sensitive to detect this low-level resistance. [3]
• discussions about the K65R mutation and the possible protective benefit from using thymidine analogues in tenofovir-containing regimens. [4, 5]
  Several studies also provided updated information on the incidence of NNRTI resistance in mother to child transmission programmes using single-dose nevirapine and these are covered in detail by Polly Clayden in this issue of HTB.

A study from the UK presented for the first time at this meeting indicated that response to first-line treatment in patients who have been infected with single-class associated drug-resistant virus can be similar to response in treatment naïve individuals. The researchers commented that the response to future treatments is likely to be where the impact of the transmitted resistance becomes clinically significant through reduced treatment options. [6]

References:

1. Little SJ, Koelsch K, Ignaci C. Persistence of transmitted drug-resistant virus among subjects with primary HIV infection deferring antiretroviral therapy. 11th CROI 2004, Oral abstract 36LB.
2. Cane P, Dean G, Fisher M et al. Persistence of primary genotypic resistance following HIV-1 seroconversion for as long as three years post-infection. 11th CROI 2004, Abstract 684.
3. Mellors J, Palmer S, Nissley D et al. Low-frequency NNRTI-resistant variants contribute to failure of efavirenz-containing regimens. 11th CROI 2004, Oral abstract 39.
4. Parikh U, Koontz D, Sluis-Cremer N et al. K65R: a multinucleoside resistance mutation of increasing prevalence exhibits bi-directional phenotypic antagonism with TAM. 11th CROI 2004, Oral abstract 54.
5. White KL, Margot NA, Chen JM et al. The HIV-1 K65R RT mutant utilises a combination of decreased incorporation and decreased excision to evade NRTI. 11th CROI 2004, Oral abstract 55.
6. Pillay D, Jurriaans S, Prins M et al. The effect of transmitted drug resistance on virological response to HAART regimens adjusted for genotypic resistance at baseline. 11th CROI 2004, Abstract 685.