1. Priority Setting and Effectiveness Patrick Osewe, MD, MPH World Bank
Introduction

2. Learning Objectives
Introduce economic and ethical issues surrounding different care interventions
Share experience in prioritizing eligible populations for access to ART
Understand different policy options for scaling up access to ARV drugs
Understanding the constraints to scaling up care and support services in Africa
Share experience on how to averting possible negative consequences of scaled up treatment
Learning/Training Objectives
To introduce participants to economic and ethical issues surrounding different care interventions.
To outline and explain fair process in prioritizing eligible populations for access to ART.
To define and facilitate understanding of the different policy options for scaling up access to ARV drugs. To explain some of the constraints to scaling up access to care in developing countries.
To discuss ways of averting possible consequences of scaled up treatment.

3. Prioritizing Programs of Care for People with HIV/AIDS
What considerations are made when deciding what kind of treatment to offer for people with HIV/AIDS?
Economic
Analysis
Unit 9 examines issues related to prioritizing programs of care for people with HIV/AIDS.
Demand
Ethics
Technical
Challenges
Acceptability
Bio-
medical
need
Political
Pressure

4. Ethical Principles that are Related to Priority Setting
Justice
Human rights and dignity
The common good
Fair opportunity
Ethical Principles
Justice is the moral virtue of constant and firm willingness to give to one's neighbor that which is his or her due. Justice promotes fair, equitable, and appropriate treatment in light of what is owed to the individual.
Human dignity is the principle that accepts that humans deserve a certain standard of respect, free from needless degradation.
The common good demands that actions be taken that benefit the community.
Beneficence includes any form of action to benefit another.
Fair opportunity is the rule of social distribution that attempts to decrease unjust forms of allocation

5. Care Options for People with HIV/AIDS in Africa
Ways of improving the quality of life for people with HIV and AIDS in Africa include
Palliative care: providing supportive care and pain control
Prophylactic care against opportunistic infections
Treatment of opportunistic infections
Antiretroviral therapy
Cost Effectiveness of Care Programs for People with HIV/AIDS
DALY= Disability Adjusted Life Year
CEA is used to assess and summarize the relative value of an intervention.
This is done by measuring both the costs and the consequences of several choices of intervention that are intended to meet the same objective.
In a CEA, a researcher establishes the effectiveness of the program according to expected health impact (disability adjusted life years or cases of HIV averted can be used).

6. Costs of Palliative Care for People with HIV/AIDS in Africa
Author (Year)
Country/ Description
Cost (US$)
World Bank (1997)
Sub-Saharan Africa/ palliative care plus treatment of inexpensive OIs
$ per patient year
Uys and Hensher (2002)
South Africa/ drugs and nursing care
$400 per patient year
AIDS palliative care
This slide outlines findings from two studies from sub-Saharan Africa that assessed HIV palliative care and their associated costs. The goal of AIDS palliative care is to alleviate pain and other symptoms, provide appropriate nourishment and hydration, and prepare for a peaceful death.

7. Costs of Prophylaxis for OIs for People with HIV/AIDS in Africa
Prophylaxis for Opportunistic Infections
Author (Year)
Country/ Description
Cost (US$)
Wiktor et al. (1999)
Cote d'Ivoire/ co-trimoxazole preventive therapy
$1.50 per month
Bell et al. (1999)
Sub-Saharan Africa/ preventive therapy for tuberculosis and treatment of adverse reactions
$38.31 for 6 months
Slide 10: Relevant Slide
Prophylactic care
This slide outlines findings from studies from sub-Saharan Africa that assessed preventative care using Co-trimoxazole and TB drugs and their associated costs.
OIs are associated with mortality independent of CD4 count and their occurrence may accelerate Treatment of infections before symptoms are present is referred to as prophylactic care.

8. Costs and Cost-Effectiveness of Treatment of Opportunistic Infections in People with HIV/AIDS in Africa
Treatment of Opportunistic Infections
Author (Year)
Country/ Description
Cost (US$)
World Bank (1997)
Sub-Saharan Africa/ treatment of PCP or toxoplasmosis
$8 per patient treatment
Sub-Saharan Africa/ treatment of tuberculosis
$37 per patient treatment
Floyd et al. (1997)
Uganda/ Directly observed treatment short course (DOTS)
DOTS: $ per patient treatment
Slide 11: Relevant Slide
Treatment of OIs
Costs and cost-effectiveness (DALYs gained) of treatment of OIs, once a person is shows signs and symptoms of the OI, are outlined in this slide.

9. Costs and Cost-Effectiveness of HAART for People with HIV/AIDS in Africa
Reducing Viral Load: HAART
Author (year)
Country/ Description
Cost (US$)
Creese et al.2002
Senegal and Cote d’Ivoire
$ 1100 per year
(Cost/DALY= $1100)
Wood et al. 2000
South Africa
$ 350 per year
(Cost/DALY= $1800)
Slide 12: Relevant Slide
HAART
Costs and cost-effectiveness (DALYs gained) of HAART are outlined in this slide.

10. Potential Priority Populations for the Distribution of ART
What considerations are made when deciding which populations are offered ART first?
Economic
Productivity
Unit 10 examines potential priority populations for the distribution of ART.
Social
Productivity
Fair process
Likelihood of
adherence
Potential for
transmission
First Come
First Served
Community
Involvement

11. Potential Priority Populations for the Distribution of ART
The Issues
Deciding on who should be the first recipients of ARVs
What process must be followed in priority setting for fairness?
What Criteria? - Policy guidance on populations to be prioritized
Involving Communities in decision making
This slide examines potential priority populations for the distribution of ART Fair Process must be followed in priority setting
Criteria need to be formed that guide policy on which populations should be prioritized
Communities should be involved in decision making

12. What are the Elements of Fair Process?
Transparency
Community access to the rationale for decisions made
Relevant reasoning is discussed among stakeholders
Room for revising the criteria
Accountability for enforcing the criteria are adhered to
This slide outlines some suggested criteria for fair process.

13. Who are the Potential Recipients of Scaled up ARV Programs
First Come/First Served
Groups of People Based on Characteristics
The economically or socially productive sector
The poor
Those likely to adhere to therapy
Health care workers
Using ARV Drugs to Prevent HIV Transmission
Exposed health care workers and rape victims
HIV infected mothers (PMTCT)
Those at risk of transmitting HIV
Sex workers/High risk men
This slide outlines a number of possible methods for arriving at priority populations for HAART
Priority may be assessed based on First Come/First Served; Social, behavioral or bio-medical characteristics; or their ability to Prevent further HIV Transmission

14. Prioritization to Receive ARVs: The Poor
Issues
Identifying the poor
Cost of testing for HIV
Cost of out-patient visits
Illiteracy
Poor nutrition
Cost of treating all HIV+ people below the poverty line in India: $280 per year of life saved
Prioritizing the Poor
This slide outlines issues associated with prioritizing the poor for subsidized HAART programs.
Even if antiretroviral drugs were to be provided free of charge, other costs would also need to be considered. These include: ELISA tests to establish HIV status; counseling; out-patient visits to monitor side-effects and to issue supplies of drugs; and laboratory tests. Funds would also have to be sought from others to finance other costs such as importation of supplies from outside of the country (which are likely to be more expensive) and the strengthening of laboratories (in order to be able to sustainable provide high-quality tests). Difficulties faced in this population such as illiteracy and poor nutrition may also need to be considered. Cost of treating all HIV+ people below the poverty line in India: $280 per year of life saved

15. Prioritization to Receive ARVs: The Economically or Socially Productive
Issues
Identifying the economically or socially productive
Some may be able to afford the drugs without subsidization (issues of fairness)
Likely to be literate and able to support other associated costs of care
Prioritizing those who are believed to be contributing most to the society
The contribution can be through either through economic or social means. It could be argued that prolonging life and improving health in certain segments of the society, everyone will benefit everyone.

16. Preventing the spread of HIV Using ARVs
ARVs have demonstrated reductions in transmission when used for
Occupational post- exposure prophylaxis
The prevention of mother-to-child transmission
ARVs are likely to reduce HIV transmission by reducing viral load, thereby making HIV less sexually
transmissible
Prioritizing based on the potential to prevent further transmission
ARV programs have the potential to prevent HIV transmission (to health care workers, victims of rape and babies of HIV positive mothers). In the general population, HAART prolongs and improves life but is not curative. The effect of using treatment as a population-level HIV prevention strategy is uncertain.

17. Post-Exposure Prophylaxis (PEP) for Occupational Exposure
Risk of HIV transmission after a needle stick injury from an HIV infected source is about 1 in 400 (or 0.25%)
Zidovudine (AZT) lowers the risk of HIV transmission from a needle stick exposure by 80%
PEP may result in cost savings in developing countries
This slide outlines the risk after exposure to HIV though needle stick or mucus membranes
The risk of HIV transmission after a needle stick injury exposure involving body fluid from an HIV infected source about one in 400 or 0.25% and about 0.09% after mucus membrane exposure (Ippolito et al., 1993). A US case-control study reported that zidovudine (AZT) lowered the risk of HIV transmission from a needle stick exposure by about 80% (Cardo et al., 1997).

18. Post-Exposure Prophylaxis (PEP) for Post-Rape
Unprotected heterosexual sex between HIV discordant couples = estimated risk of 0.2% (if the male partner is HIV+)
Risk of acquiring HIV from unprotected receptive anal sex with an infected partner is estimated to be 0.8 %
Risk of HIV infection in a rape situation would likely be higher as
There is a greater potential for other sexually transmitted diseases, trauma, and inflammation.
The risk is multiplied as more assailants are involved
This slide outlines the risk after exposure to HIV though rape
Unprotected heterosexual sex between HIV discordant couples carries an estimated risk of 0.2% if it is the male partner who is infected (Anderson & May, 1988). The risk of acquiring HIV from unprotected receptive anal sex with an infected partner is estimated to be 0.8 % (Vittinghoff et al., 1999).

19. Prevention of Mother-to-Child Transmission
The infection rates of children born to HIV infected mothers in the absence of any intervention is about 25%
Several studies have demonstrated that short courses of AZT or Nevirapine during pregnancy, reduce transmission by 50%
This slide outlines the risk after exposure to HIV though mother to child (vertical) transmission
The infection rates of children born to HIV infected mothers in the absence of any intervention is about 25% (Wiktor et al., 1999). Several studies have demonstrated that short courses of zidovudine (AZT) or nevirapine during pregnancy, sometimes in combination with other antiretrovirals, reduce transmission by as much as 50% in low-income countries depending on whether the mothers breast-fed and the type of regimen given (DeCock et al., 2000; Jackson et al., 2003; Taha et al., 2002). This intervention is extremely inexpensive. One effective combination is being used in Cameroon at a total cost of less than US $23 (Ayouba et al, 2003).
One effective combination is being used in Cameroon at a total cost of less than $US 23

20. Supplying ARVs to those Most at Risk for Spreading HIV: Population-level Prevention
ARVs can
reduce the viral load of HIV, a major determinant of HIV transmission
potentially be used to prevent the spread of HIV at a population level
If ARV treatment is shown to effectively reduce sexual transmission, who should get them?
Viral Load
? HIV transmission ?
This slide outlines the potential of HAART to reduce sexual transmission
Most studies conclude that HAART reduces the viral load of HIV-1, which is a major determinant of HIV-1 transmission from infected to uninfected people (Quinn et al., 2000). There is the potential to use ARVs to prevent the spread of HIV at a population level. If we assume that ART will effectively reduce sexual transmission, then a program could be designed to prevent the spread of HIV at the population level. In order to effectively slow or reverse epidemic growth, HIV viral load would need to be reduced in those people who are most at risk of spreading HIV. HIV positive people who are engaging in the riskiest sexual behavior could be targeted for an intervention to reduce HIV in the general population. ?

21. Avoiding the Pitfalls: Ways to Improve the Effectiveness of ART Programs
Side
Effects
Disinhibition
Resistance
Monitoring
Unit 11 examines ways to avoid the pitfalls of scaling up programs using ARV drugs and ways to improve the effectiveness of those initiatives.
HIV
prevention
Adherence

22. Avoiding the Pitfalls: Ways to Improve the Effectiveness of ART Programs
ARVs have the potential to benefit populations greatly
Possible adverse effects exist such as
increases in risky behavior
Resistance
side-effects
over-reliance on ARVs
Unit 11 examines ways to avoid the pitfalls of scaling up programs using ARV drugs and ways to improve the effectiveness of those initiatives.

23. Adverse Behavioural Change - 1
Even with effective viral suppression due to HAART, infection can occur
33% of men on ARVs continue to shed virus in their semen
Transmission benefits gained from a program covering 50-90% of HIV positive people with effective HAART is reversed with a 10% increase in risky behaviour
Actual coverage with HAART does not usually exceed 30% of HIV positive people in industrialized countries
Transmissibility even with viral suppression
This slide describes how even with effective viral suppression due to HAART, transmission can occur

24. Adverse Behavioural Change - 2
Risky behaviour is on the rise among MSM in North America in the post-HAART era
For years, North American MSM had declining rates of HIV and STI. Some cities in the late 1990’s reported an upturn in both epidemics, especially among young MSM
In Kenya, on two separate occasions immediately following wide media coverage of “quack cures”, 100% condom use among female sex workers decreased condom use and increased HIV incidence
Adverse behavior change
Risky behavior on the rise among MSM in North America in the post-HAART era
For years, North American MSM had declining rates of HIV and STI - some cities in the late 1990’s reported an upturn in both epidemics
This change in behaviour may be more pronounced among young MSM

25. Adverse Behavioural Change - 3
PEARL OMEGA
KEMRON %
This slide outlines ways to mitigate against adverse behaviour change
Healthy media messages that encourage both positive living and reinforce safe sexual behaviour can assist with reducing the effects of disinhibition that often accompany HIV care. Cost-effective, evidence-based interventions such as peer interventions with sex workers and high risk men should be scaled up at the same level as the ART programs. Consideration should be made as to which groups in society are prioritised to receive subsidised or free treatment as a potentially preventative intervention.
Year
Source: Jha et al., 2001

26. Mitigating Against Adverse Behavior Change
Step up prevention activities that are highly effective
Healthy media messages
Positive living, but with scaled up preventive behavior
Counseling: encourage safe behavior and adherence to therapy
This slide outlines ways to mitigate against adverse behaviour change
Healthy media messages that encourage both positive living and reinforce safe sexual behaviour can assist with reducing the effects of disinhibition that often accompany HIV care. Cost-effective, evidence-based interventions such as peer interventions with sex workers and high risk men should be scaled up at the same level as the ART programs. Consideration should be made as to which groups in society are prioritised to receive subsidised or free treatment as a potentially preventative intervention. Encourage adherence to therapy to promote decreases in viral load and probably reduce the risk of transmission of HIV.

27. Side Effects - 1
Most HIV-infected people on HAART experience some side effects
A study from Botswana found that the side effects were so serious that they interfered with adherence to therapy in 9% of people on HAART
Poor management of side effects may lead to purposeful non-adherence, which in turn could lead to lowered effectiveness of the treatment and resistance
This slide emphasises the prevalence of side effects and reasons for their occurrence. Most HIV-infected people on HAART experience some side effects. A study from Botswana found that the side effects were so bad that they interfered with adherence to therapy in 9% of people on HAART (Weiser et al., 2003).

28. Side Effects - 2 Side effects from HAART include the following
Bone demineralization
Hyperlipidemia
Hyperglycemia
Gastrointestinal symptoms
Diarrhea
Rashes
Headaches
Neuropathies
Hepatotoxicity
Lactic acidosis
Hypersensitivity
Pancreatitis
Anemia
Neutropenia
This slide lists the side effects HAART
Side effects from HAART include bone demineralization, hyperlipidemia, hyperglycemia, gastrointestinal symptoms, diarrhea, rashes, headaches, hepatotoxicity, lactic acidosis, hypersensitivity, neuropathies, pancreatitis, anemia, and neutropenia (Lesho et al., 2003). Poor management of side effects may lead to purposeful non-adherence, which in turn could lead to lowered effectiveness of the treatment and resistance.

29. Mitigating Against Side Effects
Make a number of standard regimens of medications available
Treat side-effects. Offer good overall care, not just drugs
Encourage adherence to therapy
Offer appropriate nutritional support
This slide outlines ways to mitigate against side-effects
Make a number of combinations of medications available.
Treat side-effects. Offer good overall care, not just drugs.
Encourage adherence to therapy.
Offer appropriate nutritional support (high fat/ high protein foods).

30. Resistance to ARVs - 1
There is a concern that there will be widespread antiretroviral resistance resulting in mass treatment failure
One of the key accelerators of resistance is lack of adherence
A study from Botswana found that only 54% of people on ARVs reported that they had adhered to the therapy regimen
A Ugandan study reported that 70% of patients enrolled in their study had virus that was resistant to at least one antiretroviral drug
Drug resistant HIV strains are transmissible
This slide outlines issues related to ARV drug resistance
Distribution of drugs without resistance testing and/or lack of adequate supply of drugs may cause widespread antiretroviral resistance resulting in mass treatment failure (Naglekerke et al., 2002; DeVlas et al., 2002). Resistance may occur in part due to lack of adherence (Sethi et al., 2003). A study from Botswana found that only 54% of people on ARVs reported that they had adhered to the therapy regimen (Weiser et al., 2003). A Ugandan study reported that 70% of patients enrolled in their study had virus that was resistant to at least one antiretroviral drug (Weildle, 2000). Drug resistant HIV strains are transmissible (Chesney et al., 1999).

31. Resistance to ARVs-2
“HAART for all” may lead to resistance in drug regimens which are used to prevent mother-to-child transmission
Nevirapine should be reserved for mother to child treatment
Mother to child transmission programs are threatened
This slide outlines the issue of one of the major consequences that will occur if widespread ARV resistance occurs.
Antiretroviral drugs administered before and during birth and while breastfeeding prevent transmission of HIV-1 from mothers to their babies (Scotland et al., 2003). There is a possible that “HAART for all” may lead to resistance in drug regimens which to prevent mother-to-child transmission. Reserving one class of ARV (nevirapine) for mother to child treatment may alleviate some of the pressure on the virus that causes resistance.
*Note that only an estimated 5% of HIV infected mothers in developing countries currently
have access to ARVs

32. Mitigating Against Drug Resistance
Use standard regimens with fixed dose therapies
Monitor drug resistance using simplified diagnostics
Improve clinical management and build infrastructure
Work with communities to find strategies that encourage adherence to therapy
If treatment regimens are not followed, there is a greater opportunity for drug resistant strains of HIV to develop. Resistant viruses are transmitted from person to person. ART programs are more likely to remain effective if the standard regimens with fixed dose therapies are used. Training of health care workers and key community members can improve clinical management. Better health care infrastructure will allow for a more consistent supply of medications. When scaling up ART interventions, partner with communities to find strategies that encourage adherence to therapy. Drug resistance can be monitored using simplified diagnostics.

33. Conclusion
Policies written to guide ARV programs must address the following
the level of treatment to be offered
the process to be followed in prioritization
those who will be prioritised for treatment
the potential adverse effects
how those side-effects can be mitigated against
Conclusion