HTB

XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, 10-14 June 2003

1 September 2003. Related: Conference reports, Drug resistance, , .

Reports by Simon Collins, Polly Clayden, Graham McKerrow and Steve Taylor for HIV i-Base

Probably the most useful insights into the importance of future clinical developments come from the annual Resistance Workshop, restricted to around 150 researchers and this year only one HIV-positive community place. So while we’d like to bring you an in-depth report from the meeting, we will have instead to report from the abstracts. These are now available online at:
http://www.mediscover.net/journals.cfm

The abstract book repays reading, and although some of these studies were subsequently presented at the IAS meeting in Paris, among the technical presentations often focusing on the minutiae of resistance were many studies that included findings that impact directly on clinical care.

These included:

  • Increases in transmission of drug resistant virus – which was detected in 11% of cases of primary infection in Europe (abstract 117) and in 17% of drug naïve individuals in the UK (abstract 124);
  • Further discussion about coinfection and superinfection – data revealed that with coinfection, both viruses were likely to remain present over time, whereas in superinfection the new and fitter virus often outgrows the first (abstracts 62, 63);
  • Much higher rates or nevirapine resistance than previously reported from single-dose nevirapine used to prevent mother-to-child transmission, were found by looking at earlier samples and minority viral populations – at least 75% of women showed evidence of resistance to nevirapine two weeks after a single-dose during pregnancy (abstracts 78, 79);
  • Transmission of drug resistant virus does not readily revert to wild-type even in the absence of drug, and does not appear to carry substantial reduced replicative capacity (abstracts 80, 115);
  • Currently available commercial resistance assays are insufficiently sensitive to detect low level resistance and minority populations (abstract 86, and 134, 143);
  • Cross resistance between nevirapine and efavirenz can occur even in the absence of detection of key genotypic mutations detectable by population sequencing (abstracts 134, 143);
  • Some drugs continue to contribute an antiviral effect, even in the presence of mutations (d4T – abstract 133, and 3TC – abstract 140);
  • Replicative capacity results may be distorted by the presence of even low levels of wild-type virus in the assay (abstract 85);
  • The choice of concomitant nucleosides and particularly thymidine analogue in tenofovir-including regimens may protect against MDR K65R mutation (abstracts 135, 136, 137) and possible CD8 mediated responses to tenofovir resistance from a macaques study (abstract 70). Other TDF related abstracts include 29, 30, 33, and 34;
  • Indication that diversity in responses to controlling viraemia following treatment interruption (in the SSITT trial) can be explained by differences in virus, rather than host immune response (abstract 56);
  • Analysis of residual viral replication below 50 copies – and the suggestion that resistance doesn’t generally occur < 50 copies due to only localised immune responses and fails to generate HIV-specific memory cells which are required to generate new resistant variants within the memory pool (abstract 57);
  • Frequent discordant resistance profiles between plasma and the genital tract, with nucleoside-associated mutations (to AZT and 3TC) maintained in the vaginal tract up to four years after discontinuing those treatments (abstract 68). A second study showed transmission of and maintenance of AZT resistant virus on the male genital tract (abstract 83);
  • Immunological benefit of T-20 despite resistance and shift to NSI CCDR5 virus (abstract 72).

Short reports follow for each of these subjects.

Unless stated otherwise, all abstracts in the references refer to the XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, 10-14 June 2003 and are published as part of Antiviral Therapy Volume 8 Issue 3.

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