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Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD.

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.

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Epidemiology of HIV Transmissed Drug Resistance Mutations. Amilcar Tanuri, MD, PhD.

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  1. 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.

  2. 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

  3. 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

  4. Transmission of Resistance in Europe

  5. Overall prevalence of TDR in German Seroconverter Cohort 1997–2007. Barbara Bartmeyer et al. PLoS ONE, 2010 , (5)10: e12718.

  6. Trend of TDR in San Francisco , USA Vivek Jain et al. PLoS ONE, December 2010 (5) Issue 12, e15510.

  7. Trend of TDR in San Francisco , USA Vivek Jain et al. PLoS ONE, December 2010 (5) Issue 12, e15510.

  8. Prevalence of Mutations with Reduced Antiretroviral-Drug Susceptibility 1082 HIV-infected Persons in the U.S. Weinstock et al. JID 2004;189:2174-80.

  9. 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.

  10. Trend of TDRM rate found in different surveys done in Rio de Janeiro .

  11. Trend of TDRM Pattern in Rio de Janeiro, Brazil.

  12. HIV Carrying DRM can be tramissed and can give rise to micro-epidemics Brenner et al. 2008; AIDS, 22(18): 2509–2515

  13. Impact in RC of DRM 11 9 5 17 Replication Capacity Wrin T, 40th ICAAC 2000

  14. Retention of DRM without ARV selection in B na C isolates in vitro. Gonzalez LM. et al. J Gen Virol. 2006 (5):1303-9.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  21. 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.

  22. 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.

  23. Grazie Thank you Obrigado

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