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Remarkable progress in access to HIV medicines, but there are still significant unmet needs…
Source: WHO, UNICEF & UNAIDS (2011 Progress Report)
• 6.65 million people in developing countries on ART by end of 2010 (~50% coverage)
• +10 million in need not yet accessing treatment
• At least +18 million people will need treatment in the future
one new infection for every 13 people who currently had HIV in 2010 for every 2 new infections, 3 people were put on ART, but 6 are still in need of ART
Resources available for HIV in low and middle income countries, 1986-2010
UNAIDS Investment Framework
SYNERGIES WITH DEVELOPMENT SECTORS
CRITICAL ENABLERS
• Social enablers Advocacy, laws, stigma etc.
• Programme enablers
Care & treatment
Male circumcision
Keeping people alive
Key populations
Child infections & maternal deaths
Condoms
OBJECTIVES
Stopping new infections
Behaviour change
BASIC PROGRAMME ACTIVITIES
UN targets for HIV by 2015
1
Halve the sexual transmission of HIV
2
Halve new HIV cases among injecting drug users
3
Eliminate new HIV infections among children and halve AIDS-related maternal deaths
4
Get 15 million people on HIV treatment
5
Halve tuberculosis deaths among people living with HIV
10
Eliminate parallel systems, to strengthen the integration of the HIV response
9
Eliminate travel related restrictions on entry, stay and residence
8
Eliminate stigma and discrimination by promoting laws and policies to realize human rights
7
Eliminate gender inequalities and sexual violence and increase capacities of women and girls
6
Close the global resource gap and achieve annual investment of US$ 22-24 bn
United Nations General Assembly High Level Meeting on AIDS, 2011
New prevention- and treatment-related targets for
2015:
50% ↓ in sexual transmission of HIV 50% ↓ of HIV among people who inject drugs 50% ↓ TB deaths in people living with HIV Eliminate new HIV infections among children and halve AIDS-related maternal deaths Get 15 million people on antiretroviral treatment
Targets are inter-related: the scientific rationale for treatment and prevention .
6/14/2012 7
Efficacy (%)
Maximum observed benefits, in major studies* Efficacy (C.I.)
HIV Vaccine (Thai RV144)
31% (1% – 51%)
Male circumcision (Orange Farm, Rakai, Kisumu)
57% (42% – 68%)
39% (6% – 60%) Microbicide (CAPRISA 004 - tenofovir gel)
Adapted from Padian et al, 2010; Abdool Karim, 2010; Grant et al , 2010; Cohen et al, 2011
Antiretroviral treatment for sero-discordant couples is the most effective biomedical intervention
44% (15% – 63%) PrEP (iPrEx - oral tenofovir/emtricitabine)
96% (72% – 99%) ART for HIV-positive partner (HPTN 052)
0 10 20 30 40 50 60 70 80 90 100 * Some studies of the same interventions showed divergent results
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
>500 350-499 250-349 200-249 100-199 50-99 <50
CD4 Count (cells/ml)
Cove
rage
The new ARV treatment target: 15 million people by 2015
0%
20%
40%
60%
80%
100%
>500 350-499 250-349 200-249 100-199 50-99 <50
CD4 Count (cells/ml)
Cove
rage
13.1 million (health)
CD4 350
15 million
Treatment for prevention
Source: Schwartlander et al, June 2011
Target 4
Treatment Reach 15 million people living with HIV with effective antiretroviral treatment
Antiretroviral treatment and coverage has grown rapidly in low- and middle-income countries, 2004–2010
Number of people (million)
(%) Coverage rate*
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*Coverage under WHO guidelines (CD4 count <350)
2004 2005 2006 2007 2008 2009 2010
0
1
2
3
4
5
6
7
8
0
10
20
30
40
50
60
70
80
Number of people on antiretroviral therapy
17 countries
42 countries
34 countries
15 countries
11 countries
Nepal Pakistan Somalia Sudan Tajikistan Tunisia Ukraine
Belarus Belize Benin Burkina Faso Cape Verde Congo El Salvador Eritrea Gabon Guatemala Guinea Guinea-Bissau Haiti Honduras Jamaica Lao PDR Lesotho Malawi Mali
Liberia Lithuania Malaysia Mauritania Mongolia Morocco Myanmar Niger Nigeria Panama Poland Rep. of Moldova Russian Fed Sao Tome and Principe Serbia Sierra Leone Sri Lanka Uzbekistan
Algeria Angola Armenia Azerbaijan Bangladesh Bhutan Bolivia Bulgaria Burundi Cameroon CAR Chad China Colombia Côte d’Ivoire Equatorial Guinea Fiji Gambia Ghana Hungary India Indonesia Kazakhstan Lebanon
Mozambique Oman Papua New Guinea Peru Philippines Senegal South Africa Suriname Togo Turkey Uganda UR Tanzania Venezuela Viet Nam Zimbabwe
Argentina Brazil Costa Rica Dominican Rep. Ecuador Ethiopia Georgia Kenya Mexico
Paraguay Romania Swaziland Thailand Uruguay Zambia
Botswana Cambodia Chile Comoros Croatia Cuba Namibia
Nicaragua Guyana Rwanda Slovakia
0%-19%
20%-39%
40%-59%
60%-79% >80%
Afghanistan DR Congo Djibouti Egypt Iran Kyrgyzstan Latvia Madagascar Maldives Mauritius
Eligible populations receiving antiretroviral treatment in low- and middle-income countries at the end of 2010
6/14/2012 12
People receiving antiretroviral treatment in low- and middle-income countries, 2002–2010
2002
7
4
2
1
0
6
5
3
Milli
on
2003 2004 2005 2006 2007 2008 2009 2010
Middle East and North Africa
Europe and Central Asia
East, South and South-East Asia
Latin America and the Caribbean
Sub-Saharan Africa
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6/14/2012 14
Slow treatment uptake costs millions of lives in low-income countries
6/14/2012 15
Coverage of health solution
Ideal uptake
Typical uptake
100%
75%
50%
25%
0% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years from availability
Millions of deaths could be averted
Can treatment be more accessible, affordable, simple and efficient?
Treatment 2.0 A programmatic approach
TREATMENT 2.0
Adapt delivery systems
Mobilize communities
POC and other
simplified monitoring
Optimize
drug regimens
Reduce costs
Objective: Achieve and sustain universal access & maximize the preventive benefits of ART
Optimizing Drug Regimens What does it mean?
Optimizing drug regimens: Major strategies for the mid- and long-term
Co-formulation (use FDCs or co-blister pack)
Reformulation (use extended release formulation; improve drug bioavailability; child-friendly formulations)
Dose adjustment (reduce toxicity, reduce pill burden/size)
New drugs (substitution to reduce toxicity or increase efficacy)
New strategies (eg: induction-maintenance; intensification)
Drug manufacturing process (improve API route synthesis and reduce cost)
Short term priorities for ARV optimization
1. Moving towards one pill once daily to optimize 1st line regimens
TDF/3TC/EFV as FDC
2. Development of more heat stable, once daily boosted PI options to optimize 2nd line regimens
ATV/r as a heat stable FDC
3. Improving pediatric drug regimens, moving from liquid to solid formulations (eg: sprinkles, dispersible tablets, adult strength scored tablets)
LPV/r sprinkles, AZT/3TC dispersible tablets, TDF/3TC/EFV dispersible and scored tablets
HIV drug pipeline: 2011
Agent Class Sponsor Status
Vicriviroc CCR5 antagnonist Schering Phase III
Elvitegravir Integrase inhibitor Gilead Phase III
Apricitabine, ATC* NRTI Avexa Phase II/III
Berivimat* Maturation inhibitor Myriad Phase IIb
UK453,061* NNRTI Pfizer Phase II
IDX889* NNRTI Indenix/GSK Phase II
GSK1349572* Integrase inhibitor GSK/Shionogi Phase Iib
GSK1265744 Integrase inhibitor GSK/Shionogi Phase Iia
PRO 140* CCR5 antagonist Progenics Phase II
Ibalizumab* CD4 antagonist Taimed Phase IIb
Gilead 9350 PK booster Gilead Phase II
* Potential activity against extensive drug resistance. Development has stopped.
Treatment is not just delivering drugs. What about early diagnosis and follow up?
Many tests are performed but patients do not get the results, compounding low coverage of essential HIV diagnostics
Based on weighted average of data from 3 SSA countries, 46% of CD4 test results were not received by the patient1,2,3,4
Sources: 1 National volumes for Mozambique, Malawi and South Africa based on CHAI data; 2 LTFU estimated based on Jani et al (2011); 3 MOH Malawi; 4 Larson et al (2011); 5 December 2008 Stocktaking Report, UNICEF
CD4 tests EID tests Based on a 2008 UNICEF stocktaking report, 51% of positive EID test results are not received by the patient5
Roughly half of all laboratory-based CD4 and EID results are never delivered to patients
51% patients not
informed
46% patients not
informed
Point-of-Care Diagnostics
HIV rapid test CD4 Some POC on the market – more to come
Viral Load No POC devices on the market –several on the pipeline
Early infant diagnosis SAMBA 1 and others
Slide courtesy of Maurine M. Murtagh and UNITAID
CD4 product pipeline (timing and sequence may change)
2009 2010 2011 2012 2013
PointCare
Partec Mini
PIMA
Daktari
Burnet mBio
Zyomyx
Instruments Disposable
Technology Pipeline – Viral Load and EID*
2011 2012 2013 2014 2015
Alere
NWGHF VL
NWGHF EID SAMBA 2
VL
SAMBA 1 EID
Liat
Wave 80 EOSCAPE
Gene XPert
Micronics
Biohelix
ALL
* Estimated. Timeline and sequence may change
Mozambique: Impact of PoC CD4 on time of ART initiation
Sitoe et al, CROI, 2010
Total time to ART initiation was reduced from 44 days to 21 days
Patient access to the initial CD4 result improved from 57% to 93%
N=849
Pricing and sustainability
Many aspects of drug quality control need improvement: Quality of drug regulatory authorities in 26 African countries
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Not mentioned
Not existing
Inadequate
Adequate
0
5
10
15
20
25
Source: World Health Organization, 2010
Local drug production is an attractive concept
Drug production requires continuous innovation. The market needs to be attractive enough for companies to invest. Investment needs to ensure sufficient, stable supplies.
Pessimists are vocal: “Local production of drugs to guarantee affordability and sustained supply is a romantic idea”
National AIDS Programme manager, Brazil
Median transaction prices in 2009 US$ per person/per year (25th – 75th Quartile range)
South Africa (local production)
Low-income countries
Lower middle-income countries
Upper middle-income countries
204 (58 – 248)
41 (39 – 48)
42 (41 – 43)
43 (42 – 45)
183 (142 – 474)
99 (94 – 118)
-
94 (92 – 97)
NVP 200 mg
ZDV 300 mg
Source: WHO Price reporting mechanism, 2010
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Price trends for ART regimens 2008-2010
0
5
10
15
15
15
20
US$ 25 Median monthly transaction price per patient
A [3TC+ZDV] +[LPV+RTV] [150+300]mg +[200+50]mg
B EFV+FTC +TDF [600
+200+300]mg
C [FTC+TDF]
+NVP [200+300]mg +200mg
D EFV
+[3TC+ZDV] 600mg +[150+300]mg
E 3TC
+NVP +d4T[150
+200+30]mg
2009
2008
2010 (1st quarter)
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Drug prices can be reduced! Ukraine 2004 vs 2009
Zidovudine (AZT)
Lamivudine (3TC)
Zidovudine (AZT) plus Lamivudine
(3TC)
Stavudine (d4T)
Evafirenz (EFV)
Nevirapine (NNRTI),
tabs
Nelfinavir
2004
2009
US$ 350
300
250
200
150
100
50
0
Source: International HIV/AIDS Alliance in Ukraine.
Treatment costs per person per year
Generic competition & treatment scale-up have cut costs
$10,400
$2,700
Lowest generic price, first-line ARV regimen
Originator generic price, first-line ARV regimen
Number of people in LMICs receiving antiretroviral treatment
A new tender strategy reduced prices for key antiretrovirals in South Africa (2008-2010 comparison)
ARV drug 2008 price (South African Rands)
2010 price (South African Rands)
Price reduction (%)
Efavirenz (600 mg tablet) R 107.07 R 39.22 63% Lamivudine (150 mg tablet)
R 29.77 R 18.22 39% Nevirapine (200 mg tablet)
R 31.53 R 22.99 27% Tenofovir (300 mg tablet) R 155.60 R 54.82 65%
How it was done: • Pre-established target prices • Encouraged all suppliers to participate, locally and internationally • Ensured adequate products were registered with the Medicines Control Council (MCC) • Published a reference price list based on international transactional prices • Suppliers were required to provide a breakdown of their cost components • Price changes were monitored through the lifecycle of the tender.
Per-patient PEPFAR budget allocation is estimated as lagged treatment allocation, divided by end-of-reporting of patients directly supported on ART by PEPFAR. Budget per result estimates may vary from site-level costing estimates.
Bulk procurement has reduced ART costs: PEPFAR costs per patient, 2004-2009
Using TRIPS flexibilities: compulsory licensing of Efavirenz, Brazil 2007
Annual cost – decreased from US$ 580 (brand) to US$166 per patient per year (Indian generic)
Estimated “savings” until 2012 - US$ 237 millions – long term sustainability – new patients, 3rd line drugs In 2007 alone – expenditure with EFZ dropped from US$ 42 millions to US$ 12 millions National production started in 2009
The future is happening right now: Migration from 1st to 2nd line treatment
Region Annual Rate of Migration
Africa 2.6%
Latin America 2.6%
South-East Asia 1.1%
Western Pacific 1.1%
Other Regions 1.9%
Countries using routine viral load monitoring
6.0%
Source: Systematic review by WHO and Australian National Centre in HIV Epidemiology and Clinical Research (CROI 2010)
Long term treatment programs: 25% ‒ 30% of patients are on 2nd line treatment
Service delivery and community mobilization
Major causes of loss to follow-up in the care continuum framework
Stigma
Transport costs
Loss of income
Prolonged waiting times
High frequency of clinic visits
Treatment and health illiteracy
Poor linkages between services
Over-burdened healthcare systems
Same people, same behaviour… different doors
Scaling up HIV treatment in Thyolo, Malawi, through decentralization and task shifting
Bemelmans M et al. Providing universal access to antiretroviral therapy in Thyolo, Malawi through task-shifting and decentralization of HIV/AIDS care. Tropical Medicine and International Health, 2010, 15(12):141.
Access to ART in:
Time to ART initiation decreased from nearly 100 days in 2003 to less than 3 weeks in 2009.
Better outcomes through decentralization of ART service delivery in South Africa
Patients at primary healthcare facilities had:
Better retention in care
Lower mortality rates
Non-inferior virological suppression
Fatti G, Grimwood A, Bock P (2010) Better Antiretroviral Therapy Outcomes at Primary Healthcare Facilities: An Evaluation of Three Tiers of ART Services in Four South African Provinces. PLoS ONE 5(9): e12888. doi:10.1371/journal.pone.0012888
Delivering home-based HIV services Jinja District, southeast Uganda
Home-based and facility-based treatment costs were broadly comparable.
Patient costs to access care were 50% lower in the first year for those receiving home-based care, and 66% lower thereafter.
Treatment outcomes and rates of loss to follow-up were similar in both groups
Shabbar J et al. Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial . Lancet 2009; 374 (9707): 2080–2089
Impact of community groups on ART delivery and retention in Mozambique
There was an approximately 4-fold reduction in medical consultations among patients receiving CAG-based care.
Number of patients Median follow-up time
1384 12.9 months
# Patients remained on care 1269 (97.5%)
# Patients transferred out 83 (6%)
# Deaths 30 (2%) # Lost to follow-up 2 (0.2%) Decroo, Tom et al., Distribution of
Antiretroviral Treatment Through Self-Forming Groups of Patients in Tete Province, Mozambique. JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2011 - Volume 56 - Issue 2 - pp e39-e44 doi: 10.1097/QAI.0b013e3182055138
What is needed to meet the challenge of scale up?
Radical simplification (treatment algorithm, drugs, services)
Innovation (in drug design, diagnostics, delivery)
Efficiency gains
Effectiveness and impact
Equity and affordability (at individual and system level)
Leadership, willingness and resources to invest
The challenges posed by ‘15 by 15’
Financing Cost and complexity of treatment Inefficiencies in and fragmentation of service delivery Treating earlier for improved and broader health outcomes - early
diagnosis Transition from emergency response to sustained chronic care
The beginning of the end of AIDS is in our hands
