WHO 2013 ARV Guidelines What's new in the WHO ART guidelines How did markets react? Dr. J. Perriëns Coordinator, HIV Technology and Commodities HIV department, WHO, Geneva
When to start in adults Starting treatment Threshold for treatment initiation moved to < 500 CD4 Priority for reaching all HIV+ symptomatic persons and those with CD4 350 More CD4-independent situations for ART initiation: HIV sero-discordant couples Pregnant women Chronic active HBV infection Children less than 5 years of age September 2013
What to Start in Adults FIRST-LINE REGIMENS (PREFERRED ARV REGIMENS) TARGET POPULATION HIV+ ADULTS 2010 ART GUIDELINES 2013 ART GUIDELINES AZT or TDF + 3TC (or FTC) + EFV or NVP HIV+ PREGNANT WOMEN HIV/TB CO-INFECTION HIV/HBV CO-INFECTION AZT + 3TC + NVP or EFV AZT or TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + EFV (as fixed dose combination)
What ART to Switch to TARGET POPULATION HIV+ ADULTS AND ADOLESCENTS HIV+ PREGNANT WOMEN HIV/TB CO-INFECTION HIV/HBV CO-INFECTION If d4t or AZT used in first-line If TDF used in first-line If rifabutin available If rifabutin not available WHAT TO SWITCH IN ADULTS (PREFERRED REGIMENS) 2010 ART GUIDELINES TDF + 3TC (or FTC) + ATV/r or LPV/r AZT + 3TC + ATV/r or LPV/r Same regimens recommended for adults Same regimens as recommended for adults NRTI backbone plus LPV/r or SQV/r with adjusted dose of RTV (i.e., LPV/r 400mg/400mg BID or SQV/r 400mg/400mg BID) AZT + TDF + 3TC (or FTC) + (ATV/r or LPV/r) 2013 ART GUIDELINES No change No change No change No change No change No change
When to start in children AGE GROUP 2010 RECOMMENDATIONS <1 YEARS Treat ALL Strong recommendation, moderate-quality evidence 1-2 YEARS Treat ALL Conditional recommendation, very-low-quality evidence 2-5 YEARS Initiate ART with CD4 count 750 cells/mm3 or <25%, irrespective of WHO clinical stage AGE GROUP 2013 RECOMMENDATIONS < 1 YEARS Treat ALL Strong recommendation, moderate-quality evidence 1-5 YEARS Treat ALL Conditional recommendation, very-lowquality evidence Priority: children < 2 years or WHO stage 3-4 or CD4 count 750 cells/mm3 or < 25% 5 YEARS CD4 count 350 cells/mm3 (As in adults), irrespective of WHO clinical stage AND WHO clinical stage 3 or 4 5 YEARS CD4 500 cells/mm3 Conditional recommendation, very-lowquality evidence CD4 350 cells/mm³ as a priority (As in Adults) Strong recommendation, moderate-quality evidence
Age group What ART to start: age < 3 years Prior exposure to PMTCT ARV s 2010 recommendations 2013 recommendations <12 months Exposed LPV/r + 2 NRTIs LPV/r plus 2 NRTIs Not Exposed Exposure unknown If LPV/r not available, NVP-based 12 to <36 months Regardless of exposure NVP + 2 NRTIs AZT + 3TC ABC + 3TC d4t + 3TC Plus NRTI backbone: AZT or ABC + 3TC (d4t+3tc*) When HIV RNA monitoring is available, consider to substitute LPV/r with NNRTI after virological suppression is sustained (conditional, low quality)
Monitoring response RECOMMENDATION Viral load is recommended as the preferred monitoring approach to diagnose and confirm ARV treatment failure If viral load is not routinely available, CD4 count and clinical monitoring should be used to diagnose treatment failure Test viral load Viral load >1000 copies/ml Evaluate for adherence concerns Repeat viral load testing after 3 6 months Viral load 1000 copies/ml Maintain firstline therapy Viral load >1000 copies/ml Switch to second-line therapy
What happened in the market? Adult treatment: proportion of patients treated with each of the primary nucleosides 70% 60% 50% 40% 30% 20% d4t AZT TDF ddi ABC CADO 1 June 2010 10% SUFA 1 SUFA 2 MULTIPLE CONSULTATIONS ON GL 0% 01/12/2010 01/06/2011 01/12/2011 01/06/2012 01/12/2012 01/06/2013
45% 40% Relative uptake of different tenofovir containing formulations AUROBINDO JUN 13 USFDA 35% Efavirenz (EFV) + Emtricitabine (FTC) + Tenofovir (TDF) 30% 25% 20% MSD 2007 15% MYLAN 10% OCT 10 5% CIPLA DEC 11 HETERO AUG 12 USFDA AUROBINDO FEB 13 USFDA Efavirenz (EFV) + Lamivudine (3TC) + Tenofovir (TDF) Emtricitabine (FTC) + Tenofovir (TDF) Lamivudine (3TC) + Tenofovir (TDF) Tenofovir (TDF) MYLAN 0% OCT 10 01/12/2010 01/12/2011 01/12/2012
4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% Proportion of adults treated with any protease inhibitor, with LPV/r, with ATV, and with other PI's Proportion of adults treated with any third line drug 0.012% 0.010% 0.008% 0.006% 0.5% 0.0% 01/12/2010 01/12/2011 01/12/2012 % of all PI in adults treatment LPV/r ATV All other PIs Linear (% of all PI in adults treatment) 0.004% 0.002% 0.000% 01/12/2010 01/12/2011 01/12/2012 % of all 3rd line drugs in adults treatment
60.0% Market share (% of children-years sold) of pediatric formulations in 2012-13 50.0% 50.8% 40.0% 30.0% 20.0% 20.8% 10.0% 0.0% 2.5% 2.6% 2.8% 2.8% Other * LPV/r ZDV 3TC + d4t ABC + 3TC NVP 3TC + ZDV 3TC + NVP + d4t 3.6% 5.3% 8.8% 3TC + NVP + ZDV * Includes d4t 0.2%; EFV 0.7%; ABV 0,6%; 3TC 0.7%; and ddi 0.3%
Trends in the use of pediatric formulations (% of children on treatment using) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 01/12/2010 Oral liquid formulation 01/12/2011 [3TC + NVP + d4t] and [3TC + d4t] and [d4t] 01/12/2012 Solid formulations
Towards 2015 Additional 1 st line options Better 2 nd / 3 rd lines New strategies (if proven effective) New drugs and new combinations shall be made available, globally, at reasonable price and possibly as FDCs Nucleosides Integrase Inhibitors Non-nucleosides Protease Inhibitors Available agents / combinations Raltegravir Rilpivirine (FDC) Darunavir (boosted FDC) Elvitegravir (FDC) Dolutegravir (FDC) Investigational agents / combinations TAF (TDF prodrug) MK-1439 TMC 310911