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Successes and Challenges of Roll-out of ART  in Low-Income countries Lut Lynen Institute of Tropical Medicine, Antwerp
 
 
Many more….
1981: “The beginning of AIDS”
Antiretroviral therapy and management of HIV infection. Paul A Volberding, Steven G Deeks Lancet 2010; 376:49-62
Approved antiretrovirals + Darunavir + Maraviroc + Raltegravir NNRTI 1987 1991 1992 1994 1995 1996 1997 1998 1999 2000 1988 1989 1990 NRTI Fusion Inhibitors Ziagen Combivir Videx Retrovir Zerit Hivid Epivir Trizivir Viramune Rescriptor Sustiva Norvir Invirase Agenerase Crixivan Fortovase Kaletra Viracept 2001 Viread 2002 2003 Reyataz PI FUZEON Emtriva
http://www.nature.com/nature/journal/v466/n7304_supp/pdf/nature09240.pdf
VOILÀ CE QU'UN MALADE DU SIDA  DOIT AVALER CHAQUE SEMAINE,  SANS GUERIR POUR AUTANT
Long term viral suppression Near normal life expectancy
 
 
Bridging the gap Momentum scaling up
 
Total available resources  for AIDS 1986-2008 13 billion 2008 [i] 1996-2005 data: Extracted from 2006 Report on the Global AIDS Epidemic (UNAIDS, 2006); [ii] 1986-1993 data: Mann.&. Tarantola, 1996 Notes : [1] 1986-2000 figures are for international funds only;  [2]  Domestic funds are included from 2001 onwards 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 US$ million 292 1623 8.3 billion Signing of Declaration of Commitment on HIV/AIDS,UNGASS 1995  2000 2005 1987 1990 Less than  US$ 1 million  59 212 World Bank MAP launch  Global Fund  PEPFAR 257 UNAIDS  Gates Foundation  10 000 8.9 billion 10 billion 7.1 Source :  UNAIDS & WHO unpublished estimates, 2007
 
 
« AIDS exceptionalism »
Price reduction through generic competition 3TC-D4T-NVP
ART scale up in the Developing World ,[object Object],[object Object],[object Object],[object Object],[object Object]
10 million by 2010!
 
Since 1996 the availability of effective treatment, has saved some 2.9 million lives…
Decline in TB incidence Source: Botswana MOH TB control program report to the Global Fund; mortality Central Statistical Office; ART, MOH; WHO, Botswana Triangulation 2005-6.
Challenges
ART has helped to dispel stigma and generate unprecedented demand for HIV services
Ongoing challenges
Late initiation of treatment in Sub-Saharan Africa leads to high initial mortality ART-LINC
Confronting reality ,[object Object],Egger M, 14 th  CROI, Los Angeles 2007, #62. Late!
Early Mortality- The Case For early HIV Diagnosis and Care (community based ART program SA) SOURCE: S Lawn et al:  AIDS; 22 : 1897–1908 (2008)
 
Pediatric diagnosis and treatment 15% of HIV-exposed infants receive an HIV test within the two first months of life 28 % 28% of eligible children on ART
Use of simple 1 st  and 2 nd  line regimens AZT + 3TC + LPV/r TDF + 3TC or FTC + LPV/r TDF + 3TC or FTC + NVP AZT + 3TC + ATV/r TDF + 3TC or FTC + EFV AZT + 3TC + NVP TDF + 3TC or FTC + ATV/r AZT + 3TC + EFV Preferred 2 nd  Line Options Preferred 1 st  Line Options
Projected need for second-line ARV  ,[object Object],WHO working group, HIV Department, May 2007
Very few patients are on second-line regimens in LMIC WHO 2010: Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector
How do we suspect/diagnose treatment failure? VL>10,000 FIRST  VL SECOND CD4 THIRD symptoms LATE DETECTION OF TREATMENT FAILURE Time Amount of CD4 or Amount of Virus ARV success ARV not success -  Virus -   CD4
Not available EXPERT OPINION, not EVIDENCE-BASED
10 12 10 8 Report Setting WHO Criteria Sens % PPV % An et al.  2003 2006 2006 2006 30 20 24 27 21 17 17 33 Uganda Rwanda South Africa Meya et al. Van Griensven Mee, P. et al Cambodia
Using VL to better decide when to switch ART Two possible approaches… Targeted  Viral Load Routine  Viral Load To avoid unnecessary switching To detect early  adherence problems
Role of Point-of-Care Technologies
Coverage of TB services for PLWHIV, 2009, SSA 1000 new HIV cases ART eligible =44% Know HIV status =33% Screened for  TB= 5% Incident TB in PLWHV=3% TB-ART=0.5% IPT=0.2% UNAIDS 2010, WHO Global TB report 2009 On ART = 16% 67% Does not know the HIV status
How many start ART? HIV Tested HIV-infected CD4/results Eligible for ART  Start ART  2,775 1,467 605 368 154 (42%) Failure to  obtain CD4 Failure to  start ART when eligible Median time to ART initiation:  100 days Bassett et al.  AIDS  2010 – slide from Walenski R
Attrition
 
 
  Focus is on reporting ART cohorts  ART COHORT
15% defaulted before the start of ART and more than half had died before the first ART initiation visit
Retain people in care! Tracing LTFU!
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Patients’ perception
 
START ART EARLIER !! With better drugs… Viral load accessible  Infant diagnosis  Long term retention  Community involvement Social support systems
                 Zambia, Fredrick Sinyinza START ART EARLIER !! The number of people estimated to be in need of antiretroviral therapy at the end of 2009 increased from 10.1 million to 14.6 million [13.5 million–15.8 million]  WHO report 2010 Dear Lut, “ With the implementation of the new guidelines rolling out of ART is not without challenges. At one of the main sites, where I work, the number of pt starting HAART since we started using the new guidelines ( late sept this yr)  has increased by 37% ( considering pts with  WHO stage 1,2 and CD4 200-350)),  as a result the clinic has become congested, the patients are complaining and the lab is complaining (too many specimens).”
 
Patients  (%) stratified by CD4 count soon  after diagnosis (Swiss Cohort) M. Battegay, M. Rickenbach et al. 200 350
05/03/11
With better drugs… Second line ART is 10 x  more expensive! Alternative first line ART is 3 x  more expensive!
 
At Front Lines, AIDS War Is Falling Apart By  DONALD G.  McNEIL  Jr. Published: May 9, 2010 As the Need Grows, the Money for AIDS Runs Far Short By  DONALD G.  McNEIL  Jr. Published: May 9, 2010
13 Billion
Take-home message MORE MONEY  FOR AIDS LESS AIDS FOR THE MONEY There is no excuse Far too many lives are at stake And there is not enough money
Long term retention?
Mambo? Sawa Shida --------
DIRECÇÃO PROVINCIAL DE SAÚDE TETE MOÇAMBIQUE Community  ART Groups TOM DECROO
13 %   HIV (2007) 31 %   ART coverage 20 %   lost to follow up Tete
[object Object],[object Object],[object Object],[object Object],[object Object],please find here latest link http://vimeo.com/12765892   
Take-home message Be creative

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Dec2010 1final ll

  • 1. Successes and Challenges of Roll-out of ART in Low-Income countries Lut Lynen Institute of Tropical Medicine, Antwerp
  • 2.  
  • 3.  
  • 6. Antiretroviral therapy and management of HIV infection. Paul A Volberding, Steven G Deeks Lancet 2010; 376:49-62
  • 7. Approved antiretrovirals + Darunavir + Maraviroc + Raltegravir NNRTI 1987 1991 1992 1994 1995 1996 1997 1998 1999 2000 1988 1989 1990 NRTI Fusion Inhibitors Ziagen Combivir Videx Retrovir Zerit Hivid Epivir Trizivir Viramune Rescriptor Sustiva Norvir Invirase Agenerase Crixivan Fortovase Kaletra Viracept 2001 Viread 2002 2003 Reyataz PI FUZEON Emtriva
  • 9. VOILÀ CE QU'UN MALADE DU SIDA DOIT AVALER CHAQUE SEMAINE, SANS GUERIR POUR AUTANT
  • 10. Long term viral suppression Near normal life expectancy
  • 11.  
  • 12.  
  • 13. Bridging the gap Momentum scaling up
  • 14.  
  • 15. Total available resources for AIDS 1986-2008 13 billion 2008 [i] 1996-2005 data: Extracted from 2006 Report on the Global AIDS Epidemic (UNAIDS, 2006); [ii] 1986-1993 data: Mann.&. Tarantola, 1996 Notes : [1] 1986-2000 figures are for international funds only; [2] Domestic funds are included from 2001 onwards 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 US$ million 292 1623 8.3 billion Signing of Declaration of Commitment on HIV/AIDS,UNGASS 1995 2000 2005 1987 1990 Less than US$ 1 million 59 212 World Bank MAP launch Global Fund PEPFAR 257 UNAIDS Gates Foundation 10 000 8.9 billion 10 billion 7.1 Source : UNAIDS & WHO unpublished estimates, 2007
  • 16.  
  • 17.  
  • 19. Price reduction through generic competition 3TC-D4T-NVP
  • 20.
  • 21. 10 million by 2010!
  • 22.  
  • 23. Since 1996 the availability of effective treatment, has saved some 2.9 million lives…
  • 24. Decline in TB incidence Source: Botswana MOH TB control program report to the Global Fund; mortality Central Statistical Office; ART, MOH; WHO, Botswana Triangulation 2005-6.
  • 26. ART has helped to dispel stigma and generate unprecedented demand for HIV services
  • 28. Late initiation of treatment in Sub-Saharan Africa leads to high initial mortality ART-LINC
  • 29.
  • 30. Early Mortality- The Case For early HIV Diagnosis and Care (community based ART program SA) SOURCE: S Lawn et al: AIDS; 22 : 1897–1908 (2008)
  • 31.  
  • 32. Pediatric diagnosis and treatment 15% of HIV-exposed infants receive an HIV test within the two first months of life 28 % 28% of eligible children on ART
  • 33. Use of simple 1 st and 2 nd line regimens AZT + 3TC + LPV/r TDF + 3TC or FTC + LPV/r TDF + 3TC or FTC + NVP AZT + 3TC + ATV/r TDF + 3TC or FTC + EFV AZT + 3TC + NVP TDF + 3TC or FTC + ATV/r AZT + 3TC + EFV Preferred 2 nd Line Options Preferred 1 st Line Options
  • 34.
  • 35. Very few patients are on second-line regimens in LMIC WHO 2010: Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector
  • 36. How do we suspect/diagnose treatment failure? VL>10,000 FIRST VL SECOND CD4 THIRD symptoms LATE DETECTION OF TREATMENT FAILURE Time Amount of CD4 or Amount of Virus ARV success ARV not success - Virus - CD4
  • 37. Not available EXPERT OPINION, not EVIDENCE-BASED
  • 38. 10 12 10 8 Report Setting WHO Criteria Sens % PPV % An et al. 2003 2006 2006 2006 30 20 24 27 21 17 17 33 Uganda Rwanda South Africa Meya et al. Van Griensven Mee, P. et al Cambodia
  • 39. Using VL to better decide when to switch ART Two possible approaches… Targeted Viral Load Routine Viral Load To avoid unnecessary switching To detect early adherence problems
  • 40. Role of Point-of-Care Technologies
  • 41. Coverage of TB services for PLWHIV, 2009, SSA 1000 new HIV cases ART eligible =44% Know HIV status =33% Screened for TB= 5% Incident TB in PLWHV=3% TB-ART=0.5% IPT=0.2% UNAIDS 2010, WHO Global TB report 2009 On ART = 16% 67% Does not know the HIV status
  • 42. How many start ART? HIV Tested HIV-infected CD4/results Eligible for ART Start ART 2,775 1,467 605 368 154 (42%) Failure to obtain CD4 Failure to start ART when eligible Median time to ART initiation: 100 days Bassett et al. AIDS 2010 – slide from Walenski R
  • 44.  
  • 45.  
  • 46. Focus is on reporting ART cohorts ART COHORT
  • 47. 15% defaulted before the start of ART and more than half had died before the first ART initiation visit
  • 48. Retain people in care! Tracing LTFU!
  • 49.
  • 50.  
  • 51. START ART EARLIER !! With better drugs… Viral load accessible Infant diagnosis Long term retention Community involvement Social support systems
  • 52.                  Zambia, Fredrick Sinyinza START ART EARLIER !! The number of people estimated to be in need of antiretroviral therapy at the end of 2009 increased from 10.1 million to 14.6 million [13.5 million–15.8 million] WHO report 2010 Dear Lut, “ With the implementation of the new guidelines rolling out of ART is not without challenges. At one of the main sites, where I work, the number of pt starting HAART since we started using the new guidelines ( late sept this yr)  has increased by 37% ( considering pts with  WHO stage 1,2 and CD4 200-350)), as a result the clinic has become congested, the patients are complaining and the lab is complaining (too many specimens).”
  • 53.  
  • 54. Patients (%) stratified by CD4 count soon after diagnosis (Swiss Cohort) M. Battegay, M. Rickenbach et al. 200 350
  • 56. With better drugs… Second line ART is 10 x more expensive! Alternative first line ART is 3 x more expensive!
  • 57.  
  • 58. At Front Lines, AIDS War Is Falling Apart By DONALD G. McNEIL Jr. Published: May 9, 2010 As the Need Grows, the Money for AIDS Runs Far Short By DONALD G. McNEIL Jr. Published: May 9, 2010
  • 60. Take-home message MORE MONEY FOR AIDS LESS AIDS FOR THE MONEY There is no excuse Far too many lives are at stake And there is not enough money
  • 62. Mambo? Sawa Shida --------
  • 63. DIRECÇÃO PROVINCIAL DE SAÚDE TETE MOÇAMBIQUE Community ART Groups TOM DECROO
  • 64. 13 % HIV (2007) 31 % ART coverage 20 % lost to follow up Tete
  • 65.

Editor's Notes

  1. effective, convenient, and relatively nontoxic. ART regimens should be chosen in consideration of a patient’s particular clinical situation. Successful treatment is associated with durable suppression of HIV viremia over years, and consequently, ART reduces the risk
  2. Virginia Hughes: Outlook for a Cure. Nature 15 July 2010
  3. Massive increase in AIDS funding, especially after the UNGASS declaration in 2002, followed by the global fund and later by PEPFAR.
  4. And treatment benefit became clear, the AIDS-related mortality began to decline in sub-Saharan Africa and the Caribbean in 2005. Different patterns have emerged in other regions. In North America and Western and Central Europe, deaths due to AIDS began to decline soon aſter antiretroviral therapy was introduced in 1996. And it is estimated that since 1996 the availability of ART has saved close to three million lives.
  5. A community based program in South Africa shows the same effect
  6. Opnieuw, gebrek aan virale lading mag geen obstakel vormen. Op basis van klinische en immunologische criteria kan je ook therapie falen vermoeden, … . vinden experts. Maar waar is de evidence?
  7. Verschillende studies hebben aangetoond dat inderdaad de diagnostische accuraatheid van de WGO crioteria laag is. Niet alleen worden slecht 24-33% van de patiënten geïdentificeerd, maar bovendien is de PPV erg laag, wat leidt tot onnodig switchen naar een tweede lijnsbehandeling
  8. Two OPD in Durban, PITC
  9. Er zitten oon cohortes in met betalende patiëte
  10. Parents and a younger daughter in Uganda have H.I.V. but only the daughter is eligible for drugs.
  11. http://www.msf.org.uk/UploadedFiles/HIV_report_No_Time_To_Quit_May_2010_201005273105.pdf While the exceptional drive and resource mobilisation since 2001 allowed us to fight effectively against the HIV/AIDS epidemic over the past years, a sense of denial has set in among the donor community about this ongoing crisis. For the past year and a half, donors have increasingly voiced concern regarding the cost, sustainability and relative priority of HIV/ AIDS, against the background of an ostensible lack of funds.Access is about sufficient available treatment slots and ART sites distributed across the country. Today already, poorer patients cannot access the ARV lifeline, and rural areas in particular are underserved.In October 2010, a donor replenishment conference is planned to mobilize funds for the period 2011−2013. Donors have already requested the Global Fund to lower its financial ambitions. In 2009, the initial estimated needs were set at USD 20 billion for 2011-2013. In 2010, this estimate was revised down in the form of two additional scenarios, USD 13 or 17 billion respectively. All three scenarios inadequately reflect demand, as none include the additional resources required to implement the new WHO guidelines on earlier treatment and improved drug regimens. These funding levels will force rationing of treatment under Global Fund grants and accepting to support sub-standard treatment. In the Democratic Republic of Congo (DRC) 283,055 people are estimated to be in need of ART (as per the old WHO initiation criteria), but by the end of 2009, only 34,967 were reportedly on treatment - roughly 12% of the need. 44On top of the existing backlog of patients waiting for care, an estimated 179,000 more people will be become eligible for ART every year (as per old WHO criteria). In 2009, the Global Fund was supporting 1,000 new initiations per month. Now the revised availability of funds for initiation has been cut six-fold to 2,000 per year . The consequence is that in DRC – in spite of the acute crisis situation - dramatically fewer patients can start ARV. However, there is not yet unified donor support for earlier treatment with an improved first-line treatment regimen. For example, PEPFAR’s director has voiced reluctance towards implementing the new WHO treatment guidelines for earlier treatment. 52 This reluctance is translating into support of a lower standard of care in recipient countries. Most governments in the region simply cannot implement such a change without donor support
  12. Padma TV, New Dehli: Despite lofty promises, many donor agencieshave not delivered. For example, the Global Fund to Fight AIDS, Tuberculosis and Malaria pledged US$10 billion a year when it was set up in 2001, but has delivered only US$3 billion a year so far. National governments are no better at fund- ing their AIDS programmes. At an April 2001 summit in Abuja, Nigeria, 52 African coun- tries pledged to allocate at least 15% of their national budgets for health. In 2007, only three (Botswana, Djibouti and Rwanda) were on track, and three others (Burkina Faso, Liberia and Malawi) had reached some targets. These slow and bureaucratic governmen These days, 92% of those receiving treatment in low- and middle-income countries take generic drugs made in India — the ‘pharmacy of the developing world’
  13. ARV = drugs, ART = therapy = broader DPS (not MISAU, as requested by DPS)
  14. ART = therapy, ARV = drugs 24% : report of MOH, end 2009 for central MBQ, more recent then national 31% of 2008