Monitoring of HIV and HCV genetic diversity: proposal for a Caribbean surveillance network

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Monitoring of HIV and HCV genetic diversity
proposal for a Caribbean surveillance network
Georges Dos Santos, Jenny Martial, Marlène Ouka
and Raymond Césaire
Laboratoire de Virologie-Immunologie and INSERM
U433Centre Hospitalier Universitaire de
Fort-de-France Université des Antilles et de la
Guyane
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HIV classification
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HIV classification
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HIV clades distribution
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HIV diversity in the Caribbean is limited but
non-B subtypes are present
Los Alamos database
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Published data on HIV subtypes in the Caribbean
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Large-scale analysis of HIV diversityin
Guadeloupe, Martinique and French Guiana

• A total of 577 Plasma collected between 1998 and
  2003
• HIV resistance genotyping (TruGene, Visible
  Genetics)
• Subtype determination using the Stanford database
• Phylogenetic analysis

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HIV subtype distribution in Guadeloupe,
Martinique and French Guiana
Dos Santos G, et al. ICAAC 2003
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Epidemiological data of non-B HIV-1 subtype in
the FWI
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French HCV surveillance 2000-2001
Deny P, et al.
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HCV Genotypes () in Martinique
Martial J et al, J Clin Microbiol 2004
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HCV-4 phylogeny
Martinique
4a Egypt
4a France
4g
4h
(93/93)
4a
4c
4k
(62/44)
Africa
4i
(97/96)
4aB
4e
4f
(99/99)
4d France
4j
Africa
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WHO HIVResnet programme
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HIV primary drug resistance

• 1993-1994 reports on the transmission of HIV-1
  resistant to NRTI or NNRTI
• 1998 case of sexually transmitted
  multidrug-resistant HIV-1 (NRTI and PI)
• In developed countries, data on the prevalence of
  HIV drug resistance to at least one ART in
  untreated patients range from 5 to 27.
• Trend estimations of HIV resistance in recently
  infected persons show discrepancies
• Relative stability ( 10) in French, Switz, and
  Canadian cohorts
• Rapid increase to 20 - 27 in British and north
  American cohorts

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HIV primary drug resistance in the FWI

• Since 1999, 12 cases in 76 ARV naïve patients
  tested (preliminary data)
• including documented cases of transmission.

• Exemples of multi drug resistance patterns found
  in primary strains

RT M41L D67N T69N M184V T215F K219E
Protease L10I R41K A71T I84V
RT D67N T69D K70R K103N M184V K219Q
P225H Protease L10I M36I M46L F53L
I54V L63P V82A
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Caribbean HIV drug resistance surveillance
networkCaribbean HIVResNet ?

• What is the level of resistance to ARV in
  circulating HIV strains?
• How is HIV drug resistance changing over time?
• Are current access to treatment programs causing
  a rapid increase in HIV resistance?
• Does the level of HIV drug resistance
  justify/require changes in preventive or
  treatment approaches?

Adapted from Lazzari S, HIVResnet, WHO
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Target Populations proposed by WHO

• Persons newly diagnosed who never received
  antiretroviral drugs
• Where possible, recently infected persons
• first pregnancy or age less than 21 ?
• Detuned ELISA and/or previous negative HIV test ?
• Treated population will not be targeted for
  surveillance though specific studies may be
  required (e.g. Proportion of failures due to
  resistance)
• Pretreatment population survey is not suggested
  by WHO.
• However, recent reports showed that some
  resistance mutations remain detectable during
  several months or years.

Adapted from Lazzari S, HIVResnet, WHO
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Treshold assessment survey / Sentinel surveillance

• Sample size
• Treshold assessment survey at least 70
  sequences so that the gt5 treshold
• is triggered by the finding of 1 sample with
  major mutations
• Sentinel study around 400-500 sequences
  (sufficient to determine if resistance
• prevalence is less than 5 or to detect
  difference/change from 5 to 10)
• Consecutive newly diagnosed persons meeting
  inclusion criteria
• Periodicity 2-3 years
• Start in urban areas with high ART access

Adapted from Lazzari S, HIVResnet, WHO
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Issues to be discussed

• Epidemiological data managment ?
• Site selection and (representative?) sampling
  strategy ?
• Sequençing reference laboratories ?
• Cost of sequencing (currently around 200-300 US)
• Diagnosis reference laboratories ?
• Type of specimens (currently plasma at -80 but
  DBS are being validated)
• Pilot studies with standardized protocols ?
• Pol gene sequençing to provide drug resistance
  analysis and subtyping

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Conclusion

• Non-B subtypes and recombinant forms of HIV-1
  have been introduced in the Caribbean and their
  spread has to be surveid.
• Such variants might interfere in the future with
  vaccine trials.
• Transmission of drug resistant HIV is inevitable,
  and has to be carefully monitored at the
  population level.
• The time to expend HAART in the Caribbean is now.
• Simultaneous development of adequate
  infrastructure, uninterrupted supply of ARV,
  adherence programs, and evidence-based choice of
  treatment lines are warranted.

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