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HIV Drug Resistance Control: the Latin American experience

HIV Drug Resistance Control: the Latin American experience. Giovanni Ravasi Pan-American Health Organization, Brazil ravasigi@paho.org International AIDS Conference, Washington D.C, 22 July 2012 HIV Drug Resistance Surveillance and Control: A Global Concern.

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HIV Drug Resistance Control: the Latin American experience

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  1. HIV Drug Resistance Control: the Latin American experience Giovanni Ravasi Pan-American Health Organization, Brazil ravasigi@paho.org International AIDS Conference, Washington D.C, 22 July 2012 HIV Drug Resistance Surveillance and Control: A Global Concern

  2. Antiretroviral treatment in Latin America and the Caribbean “Antiretroviral Treatment in the Spotlight” • 521.000 people under ART - 63% regional coverage (Dec 2010) • 72,6% (1st line), 23,7% (2nd), 3,7% (3rd). • 63% of 1st line and 33% of 2nd regimens consistent with WHO. 63% 33%

  3. PAHO HIV Drug Resistance Strategy WHO HIVDR strategy introduced in the Caribbean in 2006 and Latin America in 2007. Technical cooperation provided to 30 countries (13 Latin America/17 Caribbean) for the development of HIVDR prevention and assessment strategies in 2008-2012. Key elements in Latin America and Caribbean: • Early Warning Indicators (EWI) • HIVDR surveillance and monitoring • Transmitted Drug Resistance (TDR) systematic review

  4. 1. HIVDR Early Warning Indicators • 24 countries reported EWIs (2010-2011): 8 LA/ 16 CAR • Regional EWI summary results published in 2011/2012.

  5. 2. HIVDR Surveillance and Monitoring HIVDR Surveillance: • Mexico (2004) - Bertagnolio et al • Brazil (2007-2008) - Inocencio et al - adapted* • Panama (2008-2010) - Castillo et al - adapted* * Genotyping not performed in WHO accredited labs. HIVDR Monitoring: • Haiti – ongoing • Guyana – ongoing

  6. Transmitted Drug Resistance (TDR) in Latin America Frentz et al. AIDS Rev. 2012 • 26 studies (3.218 patients) with sampling time 1993-2008. TDR Prevalence Any class: 6,3% (5,5-7,3%) NRTI: 3,8% (3,2 – 4,6%) NNRTI: 1,6 (1,2-2,1) PI: 2,4 (2,0 – 2,8%) Time trends (<2001 - >2003): NRTI decreased 6,6 to 2,8% (p<0,001) NNRTI increased 0,6 – 2,7 (p<0,001) PI increased 1,6 to 2,7% (p=0,01)

  7. 3. TDR systematic review Literature abstraction • 75 publications (56 articles and 19 abstracts)published between Jan 2000/Feb 2012 (11.194 individuals) • 79 surveys in Latin America and Caribbean • 87 drug resistance results: - 74 (85%) DR in chronically infected individuals • 13 (15%) TDR in recently infected individuals Sources NCBI-NIH PubMed, NIH-NLM Gate Way, Embase, WHO Global Health Library, BIREME BVS, SciELO. Abstracts from CROI, IAS, IAC, HIVDR International Workshop.

  8. 3. TDR systematic review Subregional distribution of surveys • 39 (49%) Brazil • 16 (20%) Southern Cone - no data for Paraguay and Uruguay • 8 (10%) Andean Region - no data for Ecuador and Bolivia • 7 (9%) Central America - no data for Nicaragua and Costa Rica • 6 (8%) México • 3 (4%) Caribbean - only Dominican Republic and Cuba

  9. 3. TDR systematic review Population type 64 (81%) mixed population, 4 pregnant women, 3 blood donors 4 MSM, and others (2 IDU; 1 FSW; 1 army soldiers) HIV Genotyping method 40 (62%) In House, 13 (20%) Viroseq, 12 (18%) Trugene Reference for DR mutations WHO list (2007-2009) of TDR mutations used in 28% papers after 2007. Results have been revised according to WHO 2009 list. WHO TDR categories to classify results: Low <5%; moderate 5-15%; high >15%.

  10. Resistance to any ARV class

  11. Resistance to individual ARV classes

  12. Brazil Prevalence of TDR shows geographic specificities with areas of low, moderate and high resistance. .

  13. Multiple class drug resistance (MDR) • No evidence of MDR in the Caribbean. • Very limited evidence (<1%) of MDR in Southern Cone, Central America, Andean Region (recently infected), Brazil and Mexico TAMs (≥3 mutations) • No evidence in the Andean Region, Central America, Caribbean • Very limited evidence (<1%) in Southern Cone, Brazil and Mexico. K65R (TDF mutation) • No evidence in the Andean Region, Southern Cone, Caribbean, Brazil and Mexico • In Central America: 1 sample with K65R only in 1 study in 2003.

  14. Common methodological limitations • Convenience sampling (or no sample size calculation presented). • Small sample size (<47- 54% surveys in recently / 22% in chronically infected subjects). • Long sampling time periods (>3 years in 24%; max 7 years) • Different survey populations (recently infected, recently diagnosed, pre-ART). • Different definitions of “recently infected”. • Different TDR mutation lists (IAS, Stanford, WHO, ANRS, etc.).

  15. Conclusions (1) - Prevalence and patterns of TDR vary across subregions. - HIVDR surveillance should be expanded. • Standardized and representative methodology. • Generic protocols for HIVDR surveillance (countries with low HIV prevalence; MARPs). • Full scale national HIVDR surveillance (TDR/pre-ART) when confirmed evidence of moderate resistance. - Use of HIVDR data for public health actions is a challenge. • Guidance for interpretation and programmatic use of HIVDR surveillance data is needed to support National Programs (especially in case of moderate-high resistance).

  16. Conclusions (2) Is important to strengthen HIVDR prevention • HIVDR prevention activities should be supported and strengthened at country level (EWIs, Treatment 2.0 and optimization, stock-out surveillance, prevention for positives, etc.). More operational research is needed • Support operational research on impact of low/moderate single class/multiple class TDR on first line effectiveness.

  17. PAHO HIV ProjectMassimo GhidinelliOmar SuedMonica AlonsoNoreen JackAmalia del RiegoBertha GomezMaria Dolores Perez-RosalesMarcelo VilaAll country based HIV Focal points WHO/HQ HIVDR teamSilvia BertagnolioDiane BennettMichael Jordan Acknowledgments Thankyou Gracias Obrigado Merci

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