The XIV International HIV Drug Resistance Workshop took place between June 7 and 11 in Quebec City, Canada. At this year’s workshop there was evidence of a number of developments in areas, including prevention of mother-to-child transmission (PMTCT); epidemiology – in particular, the issue of drug transmission and its public health consequences; further understanding of the mechanisms of action of entry inhibitors, and finally some new insights into subtype variation.
Key take-home messages from the XII International HIV Drug Resistance Workshop
Prevention of mother-to-child transmission (PMTCT)
Single dose nevirapine (Viramune) leads to drug resistance. Even where resistance appears not to have occurred, more rigorous analysis using highly-sensitive detection techniques confirm that resistance is not only present but likely to be sustained over several months. Latest data further suggest that since the aim is to prevent HIV infection to the infant rather than to treat the mother, prophylactic treatment given only to the child may suffice avoiding resistance in the mother altogether.
Epidemiology
Accumulative data from public health surveillance show that current levels of reported transmission of drug resistance are likely to be under-estimates. In the setting of the developing world, transmitted resistance still remain a largely theoretical concern. Modelling studies suggest that factors such as viral fitness (which affect transmissibility) rather than an increase in treatment availability will have the biggest impact on primary drug resistance in the population. This has serious implications for ensuring that the most optimal therapy is made available especially as first and second-line regimens, given the potential for a serious long-term impact on public health.
Subtypes: resistance evolution and implications for therapy
Many clinicians have long assumed that patients are HIV-1 subtype B and have treated accordingly. The evolving epidemiology of HIV in Europe and the epidemic raging in the developing world requires a reappraisal of this assumption. Although mainstream guidance does not stipulate different treatment algorithms based upon subtype, virologists and physicians need to closely monitor genotypic reports for a more comprehensive understanding of possible discrepancies in polymorphic and primary mutational pathways between subtype B and other subtypes. Disregard for these advances in HIV subtype research is no longer acceptable and constitutes both clinical and political myopia.
Resistance to new antiretroviral drugs
Entry inhibitors are picking up pace through Phase 2 and 3 trials with the Pfizer agent furthest along the drug development pipeline. Current data on resistance evolution, replication and synergy between compounds in the entry inhibitor class remain largely in vitro, but suggest that it may be possible to sequence the CCR5 antagonists. The tricky question, say experts, will be what order to use various entry inhibitors and CCR5 antagonists.
Predicting clinical response
Cut-off values so lauded over the past few years may not prove to be the panacea for predicting drug success after all. At least, biologic values related to phenotypic changes and technical cut-off signifying limitations of assays are considered to be of little value and as such are less reported. The move is towards defining clinical cut-off values as the only meaningful indicator. This development is partly due to the longitudinal experience that now exists with a number of antiretrovirals that enable a more precise definition than was previously possible. Proficient physicians and advocates will need to distinguish and familiarise themselves with these values as well as genotypic profiles and genotypic resistance scores which combine information on drug exposure. Combined, these will provide powerful monitoring tools for informed prescribing.