slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD. PowerPoint Presentation
Download Presentation
Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD.

Loading in 2 Seconds...

play fullscreen
1 / 24

Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD. - PowerPoint PPT Presentation


  • 129 Views
  • Uploaded on

Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD. Head of Laboratório de Virologia Molecular, UFRJ, Brazil. Senior Lab Advisor ICAP, Columbia University, NY, USA. Sic Transit Gloria Mundi. Ad Majorem Dei Gloriam In Hoc Signo Vinces.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD.' - leia


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Epidemiology of HIV Transmissed Drug Resistance Mutations.

Amilcar Tanuri, MD, PhD.

Head of Laboratório de Virologia Molecular, UFRJ, Brazil.

Senior Lab Advisor ICAP, Columbia University, NY, USA.

Sic Transit Gloria Mundi.

Ad Majorem Dei Gloriam In Hoc Signo Vinces.

arv resistance in treated individuals
ARV Resistance in Treated Individuals
  • HIV DR Decreasing since initiation of triple therapy
  • DR is low in those using RTV boosted PI's
  • DR can be managed by new drugs within existing classes and new classes
transmission of drug resistance in hiv
Transmission of Drug Resistance in HIV
  • ARV treated individuals living longer
  • Incident infections continue to increase worldwide
  • Transmitted resistance well recognised in countries with wide ARV coverage
overall prevalence of tdr in german seroconverter cohort 1997 2007
Overall prevalence of TDR in German Seroconverter Cohort 1997–2007.

Barbara Bartmeyer et al. PLoS ONE, 2010 , (5)10: e12718.

trend of tdr in san francisco usa
Trend of TDR in San Francisco , USA

Vivek Jain et al. PLoS ONE, December 2010 (5) Issue 12, e15510.

trend of tdr in san francisco usa1
Trend of TDR in San Francisco , USA

Vivek Jain et al. PLoS ONE, December 2010 (5) Issue 12, e15510.

prevalence of mutations with reduced antiretroviral drug susceptibility
Prevalence of Mutations with Reduced Antiretroviral-Drug Susceptibility

1082 HIV-infected Persons in the U.S.

Weinstock et al. JID 2004;189:2174-80.

in resource rich world transmitted resistance appears to be stabilising or even reducing uk data
In resource rich world, transmitted resistance appears to be stabilising or even reducing (UK data)

14

Chronic infection

12

10

8

Samples with IAS mutation(s) (%)

6

4

Acute infection

2

0

1997

1998

1999

2000

2001

2002

2003

2004

2005

Year of sample

UK Collaborative Group on HIV Drug Resistance.

AIDS 2007;21:1035-9.

hiv carrying drm can be tramissed and can give rise to micro epidemics
HIV Carrying DRM can be tramissed and can give rise to micro-epidemics

Brenner et al. 2008; AIDS, 22(18): 2509–2515

impact in rc of drm
Impact in RC of DRM

11

9

5

17

Replication Capacity

Wrin T, 40th ICAAC 2000

retention of drm without arv selection in b na c isolates in vitro
Retention of DRM without ARV selection in B na C isolates in vitro.

Gonzalez LM. et al. J Gen Virol. 2006 (5):1303-9.

persistence of transmitted resistance in primary hiv infection

n=9

Persistent resistance

n=11

Primary resistance

n=2

Reversion to wild type

US; F/U median 9 months

n=16

Primary resistance

n=14

Persistent resistance

UK; F/U up to 3 years

n=2

Reversion to wild type

Persistence of Transmitted Resistance in Primary HIV Infection

Variable persistence according to mutations: TAMs persist, K103N persists, some PI persist (M46I, L90M), MDR can persist

Little et al. 11th CROI 2004, San Francisco, CA. Abs 36LB.

Pao et al. JAIDS 2004;37:1570-3.

dart trial zdv 3tc tdf
DART TRIAL ZDV/3TC/TDF

Prevalence of mutations at 24 and 48 weeks in absence of virological monitoring

Pillay et al. CROI 2007. Abstr. 642.

baseline resistance in dart trial
8/91 with resistance (9%)

41L,

108I,

103N+190A,

41L+70R+184V

41L,

103N+184V,

103N+181C+184V,

67N+181C+184V

Baseline Resistance in DART Trial

Drugs Compromised

Nucleoside analogues: 41L, 70R, 67N

3TC: 184V

NNRTI: 103N, 190A, 181C, 108I

  • Undisclosed Prior ART !!!!.
  • Maybe it is important to monitore cronic infected individuals in RLC.

Pillay et al. CROI 2007. Abstr. 642.

summary
Summary
  • Resistance develops following failure of therapy.
  • Resistance can be transmitted
  • Improvements in ARV regimens reduces emergence and transmission of resistance
  • Extensive resistance may develop in absence of cautious monitoring of ARV use.
  • Transmitted resistance is an important element in the new approach of “test and treat” to tackle HIV transmission.
  • Undisclosed prior ART in Resource Poor Settings can be an important element.
global distribution of hiv 1 subtypes and recombinants in 2000 2003 and 2004 2007
Global distribution of HIV-1 subtypes and recombinantsin 2000–2003 and 2004–2007.
  • The global and regional distributions of individual subtypes and recombinants are broadly stable.
  • subtype C still accounts for nearly half (48%) of all global infections.
  • CRF2_ AG doubled in 5 years.

Joris Hemelaar et al. AIDS 2011, 25:679–689

hiv 2 in the world
HIV-2 in the world
  • HIV-2 is prevalent in West Africa but can be also be found in other African Regions (Angola and Mozambique), and in Spain, Portugal, France, India, and Macau in micro-epidemics.
  • The proportion of HIV-2 in AIDS Epidemic in Angola and Mozambique is 0.6% and 0.25% , respectively.
  • HIV-2 is naturally resistant to NNRTI
  • HIV-2 accumulate more frequently Q151M mutation when compared to HIV-1 individuals treated with AZT or d4T.
dinamics of hiv 2 infection in west africa guine bissau project bandim
Dinamics of HIV-2 infection in west Africa (Guine Bissau)- Project Bandim

%

  • The amount of HIV-1/HIV-2 coinfection in west Africa is increasing and this can pose a threat to HAART therapies which target more the HIV-1.
  • HIV-1/HIV-2 coinfection in west Africa can also be a important problem for the PMTCT interventions.
final remarks
Final Remarks
  • The best way to prevent the spread of HIV DR is to prevent HIV infection.
  • The best way to prevent the spread of HIV DR is to keep the patients in ARV with undetectable VL.
  • In RLS the VL is not available in large scale.
  • 2nd line potent regimens are not available in RLS.
  • We need to make na effort to implement VL and make available potent 2nd line regimens to curb the spread of HIV DR.
slide24

Grazie

Thank you

Obrigado