The role of virological monitoring A clinical perspective Eric Goemaere MSF South Africa

Treatment simplification? HIV/TB integration PHC decentralization Task shifting Simplified treatment

Impact of routine monitoring <> Immuno- clinical monitoring on regimen change Project/ Country nMedian time on ART on second line Thyolo, Malawi M0.4 % Buhera, Zimbabwe M1.6 %

VL monitoring in LIC : a love/hate story HIV Viral Load Monitoring in Resource-Limited Regions: Optional or Necessary? Alexandra Calmy,1,5 Nathan Ford,6 Bernard Hirschel,2 Steven J. Reynolds,7 Lut Lynen,4 Eric Goemaere,8 Felipe Garcia de la Vega,1Luc Perrin,3 and William Rodriguez9,10, CID 2007:44 HIV Viral Load Monitoring in Resource-Limited Regions: Optional or Necessary? Alexandra Calmy,1,5 Nathan Ford,6 Bernard Hirschel,2 Steven J. Reynolds,7 Lut Lynen,4 Eric Goemaere,8 Felipe Garcia de la Vega,1Luc Perrin,3 and William Rodriguez9,10, CID 2007:44 More accurate assessment of treatment failure will reduce the delay in switching to second-line drugs. Targeted use of VL can limit unnecessary switching and routine use of VL can reduce the risk of resistance. WHO 2010 guidelines Keiser et al, AIDS 2011

Female, CHK Kinsahsa N° , DOB 11/10/1972 Exclusive Immuno/clinical monitoring delays clinical reaction Phase IV Oesophageal candidiasis VL VL > moved to 2 nd line Cd4 < 30 % Cd4 < 50 %

Predicting virological failure ( < 30 % of nadir CD4) in adults M. Pujades, L. Pinoges, Epicentre, not published Sensitivity = 17.2% (12.3% %) Specificity = 94.5% (93.6% %) Sensitivity = 17.2% (12.3% %) Specificity = 94.5% (93.6% %) PPV = 18.5% (13.3% %) NPV = 94.0% (93.1% %) PPV = 18.5% (13.3% %) NPV = 94.0% (93.1% %)

Predicting virological failure in children – Thailand: US IF criteria to identify children with single viral load >1000 copies/ml after 1 year of treatment (n=202) Sensitivity: 15%; PPV: 16% (Jittamala et al. 2009) – Uganda: WHO IF criteria to identify children with confirmed viral load >400 copies/ml for (n=116) Sensitivity: 0% (Ruel et al. 2010) – South Africa : criteria to identify children with VL > 1000 cp/ml ( n = 2543 ) Sensitivity 5 %, PPV= 42 % ( Mary Ann Davies, Durban Aids conference June 2011) – Thailand: US IF criteria to identify children with single viral load >1000 copies/ml after 1 year of treatment (n=202) Sensitivity: 15%; PPV: 16% (Jittamala et al. 2009) – Uganda: WHO IF criteria to identify children with confirmed viral load >400 copies/ml for (n=116) Sensitivity: 0% (Ruel et al. 2010) – South Africa : criteria to identify children with VL > 1000 cp/ml ( n = 2543 ) Sensitivity 5 %, PPV= 42 % ( Mary Ann Davies, Durban Aids conference June 2011)

Impact in early detection of VF Viral load at 3 months after initiation of antiretroviral therapy is associated with better virological and treatment outcomes than at 6 months. B. Kerschberger 1, A. M. Boulle 2, K. Kranzer 3, K. Hilderbrand 1,2, M. Schomaker 2, D.Coetzee 2, E.Goemaere 4, N. Ford 2,5, G. Van Cutsem 1,2 VL3 group : 22% less likely to experience subsequent virological failure, 27% less likely to be later switched to second line regimen

If no access to VL, priorities for VL ? Steven Van Den Broucke, Sandra Simons, Katharina Kranzer Dhodho Munyaradzi, Carol Metcalf, Kwenzakwenkosi Ncube, Helen Bygrave Poster : THPE725 Thursday 26th

Impact of late viraemia detection on horizontal and vertical transmission ? Horizontal transmission Vertical transmission – PMTCT B + : danger for subsequent pregnancies Horizontal transmission Vertical transmission – PMTCT B + : danger for subsequent pregnancies p2p3p4 HIV (+): ART: LTF: 12 M** Pre-ART Facility based HCT : Enrolled in care: LTF: 6 M Out of facility HCT : LTF:

Impact of late viraemia detection on resistance building ( TAM and K65R) Source : The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral, Therapy, Mina C. Hosseinipour & all, AIDS 23:1127–1134

Conclusions Immuno/clinical monitoring do not replace virological monitoring Key challenges are around technical/ geographical / financial access to virological monitoring Unitaid/ Chai/Unicef / MSF concerted efforts will work on all 3 aspects to make virological monitoring a reality in LIC by 2015

Acknowledgements MSF & MOH teams in Zimbabwe, RDC and South Africa Helen Bygrave, Teri Roberts,Nathan Ford All the ones fighting to be ‘ viral load undetectable’

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