HIV Resistance Testing and Subtyping the Role of the BloodBorne Virus Specialist Testing Service

1
HIV Resistance Testing and Subtyping the Role
of the Blood-Borne Virus Specialist Testing
Service Specialist Virology Centres, Edinburgh
and Glasgow

• HIV Resistance testing
• Antiretroviral drug resistance is associated with
  poor virological and clinical outcomes. Where
  genotypic resistance testing is available patient
  outcomes are improved.. There are two reasons for
  testing c.f. BHIVA guidelines)
• Baseline resistance testing (introduced April
  2005)
• As transmission of virus with reduced drug
  sensitivity is well documented, testing for
  transmitted resistance is recommended in all
  newly diagnosed patients -close to the time of
  diagnosis.
• Viral failure resistance testing (introduced
  April 2002)
• Resistance testing should be undertaken at each
  point of viral rebound on therapy. Previous
  resistance test results must be considered as
  resistance virus will be archived .Both Glasgow
  and Edinburgh labs provide clinical support with
  the resistance test results.
• HIV resistance testing methods for pol gene
• The three major classes of antiretroviral drugs
  target two regions of the pol gene
• reverse transcriptase (nucleoside reverse
  transcriptase inhibitors (NRTI) and non
  nucleoside reverse transcriptase inhibitors
  (NNRTI))
• protease (protease inhibitors (PI)).
• Resistance to a drug arises when one or more
  mutations occur in the HIV genome. These are
  detected by sequencing the reverse transcriptase
  and protease regions.
• The methods used are-
• SVC Glasgow an in-house method, developed by
  the HPA Antiviral Susceptibility Unit, Birmingham
  
• SVC Edinburgh a commercial assay (TruGene
  from Bayer).

• The two methods produce comparable results, as
  assessed by performance in external quality
  control schemes (QCMD and UK HIV working group .
  Both laboratories analyse their sequences using
  an internationally recognised and frequently
  updated web-based interpretation algorithm, the
  Stanford University HIV Drug Resistance Database
  (http//hivdb.stanford.edu) and all data is
  submitted to the UK HIV Resistance database.
• HIV resistance testing for T20
• A newer class of antiretroviral drug has been
  developed, which targets the gp41 region, encoded
  by the env gene. So far only one drug, T20
  (enfuvirtide) has been licenced in the UK.
  Resistance cannot be detected by the method
  described above this requires sequencing of
  gp41. So far 10 samples have been tested
  resistance has been seen in 4 of these.

HIV subtyping for Scotland All new diagnoses are
subtyped for HIV provided sufficient RNA can be
detected. In 2004-05 the proportion of subtype B
infections, historically associated with MSM and
IDU in developed countries, continued to decline,
such that for the first year the majority of
specimens typed (53) are now non-B subtypes.
However, it is noticeable that this proportion is
even higher in samples from Glasgow compared to
Edinburgh (58 cf. 44) where there was also a
greater diversity of subtypes- presumably
reflecting the wider ethnic diversity in the
population. Subtype C is still the most common
non-B subtype and is generally associated with
infections in Southern Africa and the Indian
subcontinent. Other notable subtypes are the A/G
and A/E recombinants that are associated with
West Africa and SE Asia respectively. We continue
to identify the occasional individual harbouring
complex recombinant viruses composed of a number
of subtypes such as A/B/A and A/B/D. In 2005-06
the number of nonB strains coming into Scotland
appears to have stabilised. This reflects the
increase of HIV in MSMs which is predominately
subtype B.