HIV Drug Resistance Control: the Latin American experience

Giovanni RavasiPan-American Health Organization, Brazil

ravasigi@paho.org

International AIDS Conference, Washington D.C, 22 July 2012HIV Drug Resistance Surveillance and Control: A Global Concern

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%

PAHO HIV Drug Resistance StrategyWHO 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:1. Early Warning Indicators (EWI)2. HIVDR surveillance and monitoring3. Transmitted Drug Resistance (TDR) systematic review

1. HIVDR Early Warning Indicators

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

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

2. HIVDR Surveillance and Monitoring

Transmitted Drug Resistance (TDR) in Latin AmericaFrentz et al. AIDS Rev. 2012• 26 studies (3.218 patients) with sampling time 1993-2008.

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)

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%)

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

3. TDR systematic review

Sources

NCBI-NIH PubMed, NIH-NLM Gate Way, Embase, WHO Global Health Library, BIREME BVS, SciELO. Abstracts from CROI, IAS, IAC, HIVDR International Workshop.

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

3. TDR systematic review

3. TDR systematic review

Population type64 (81%) mixed population, 4 pregnant women, 3 blood donors4 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%.

Resistance to any ARV class

Resistance to individual ARV classes

Brazil

.

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

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.

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.).

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).

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.

PAHO HIV ProjectMassimo GhidinelliOmar SuedMonica AlonsoNoreen JackAmalia del RiegoBertha GomezMaria Dolores Perez-RosalesMarcelo Vila

All country based HIV Focal points

WHO/HQ HIVDR teamSilvia BertagnolioDiane BennettMichael Jordan

Thank you

Gracias

Obrigado

Merci

Acknowledgments