Program: Anti-Retroviral Therapy (ART) to treat HIV/AIDS

Sources

• Antiretroviral Therapy Cohort Collaboration. 2008. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies. Lancet 372: 293-9.
• AVERT. HIV & AIDS in Botswana. http://www.webcitation.org/archive?url=http://www.avert.org/aids-botswana.htm&email=info@givewell.net (accessed April 16, 2010). Archived by WebCite® at http://www.webcitation.org/5p2oaKxqE.
• Centers for Disease Control and Prevention. Effect of Antiretroviral Therapy on Risk of Sexual Transmission of HIV Infection and Superinfection. http://www.cdc.gov/hiv/topics/treatment/resources/factsheets/art.htm (accessed October 28, 2010). Archived by WebCite® at http://www.webcitation.org/5toWmi1Op.
• Copenhagen Consensus. Copenhagen Consensus 2008. http://www.copenhagenconsensus.com/Default.aspx?ID=953 (accessed April 16, 2010). Archived by WebCite® at http://www.webcitation.org/5p2vqZV71.
• Gates Foundation. Working with Botswana to confront the AIDS crisis. http://www.gatesfoundation.org/learning/Pages/Botswana-ACHAP-AIDS-progress.aspx (accessed April 16, 2010). Archived by WebCite® at http://www.webcitation.org/5p2vuDHuy.
• Global Fund. Innovation and impact (2010) (PDF).
• Jamison, Dean T. et al., eds. 2006. Disease control priorities in developing countries (2nd edition) (PDF). Washington DC: Oxford University Press and The World Bank.
• Jamison, Dean, Prabhat Jha, and David Bloom. 2008. Copenhagen Consensus 2008 challenge paper: Diseases (PDF).
• Lopez, Alan et al., eds. 2006. Global burden of disease and risk factors (PDF). New York: Oxford University Press.
• Rutherford, G., P. Sangani, and G.E. Kennedy. 2000. Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection. Cochrane Database of Systematic Reviews 2003, Issue 4. Summary available at http://www.cochrane.org/reviews/en/ab002037.html (accessed April 16, 2010). Archived by WebCite® at http://www.webcitation.org/5p2vrBI7s.
• WebMD. HIV: Taking antiretroviral drugs. http://www.webmd.com/hiv-aids/taking-antiretroviral-drugs-for-hiv-infection (accessed July 8, 2010). Archived by WebCite® at http://www.webcitation.org/5r4mPqn0x.
• William J. Clinton Foundation. Access programs. http://www.clintonfoundation.org/what-we-do/clinton-hiv-aids-initiative/our-approach/access-programs (accessed April 16, 2010). Archived by WebCite® at http://www.webcitation.org/5p2vqyfYp.
• William J. Clinton Foundation. Antiretroviral price list (2009) (PDF).
• William J. Clinton Foundation. Annual report (2007) (PDF).
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• 1. "Taking antiretroviral drugs for HIV will not cure your infection. But it may allow you to stay healthy for a long time." WebMD, "HIV: Taking Antiretroviral Drugs."
• 2. "Combination therapy with multiple antiretroviral drugs is associated with prolonged survival. Whereas monotherapies are associated with one year or less of additional survival, the survival benefit conferred by combination therapy appears to be sustainable for extended periods (Palella and others 2003). Long-term toxicities related to treatment may include athero- sclerosis, lipodystrophy, hepatic failure, and cardiac failure. Researchers are still evaluating the effects of these toxicities on HIV/AIDS mortality." Jamison et al. 2006, Pg 355.
• 3. "Antiretroviral therapy is effective in reducing viral load and partially enabling immune restoration, thereby preventing the onset and recurrence of opportunistic infections. If taken strictly according to directions, antiretroviral therapy can induce a sustained recovery of CD4 cell reactivity against opportunistic pathogens in severely immunosuppressed patients (Li and others 1998). The effectiveness of antiretroviral therapy is determined by its ability to rapidly reduce viral load and to sustain low levels of viral activity. This viral activity is what has an independent effect on increasing or decreasing sus- ceptibility to opportunistic infections (Kaplan and others 2001)." Jamison et al. 2006, Pg 354.
• 4. "In addition to the benefits antiretroviral therapy has for the individual being treated (Komanduri and others 1998; Ledergerber and others 2001), it almost certainly has other effects on populations where therapy is widely available. Effective antiretroviral therapy appears to decrease the infectiousness of treated individuals. Chemoprophylaxis in exposed, uninfected people may reduce transmission. In addition, availability of treatment may destigmatize the disease and make prevention programs more effective (Castro and Farmer 2005)." Jamison et al. 2006, Pg 349.
• 5. "Initiating antiretroviral therapy has a proven benefit for patients with a CD4 count of fewer than 350 cells per cubic millimeter (Palella and others 2003). In patients with a higher CD4 count, the benefits of antiretroviral therapy are believed to be outweighed by the toxicities that may accrue from continued drug exposure (Mallal and others 2000)." Jamison et al. 2006, Pg 357.
• 6. "With certain drugs, resistance can develop in as little as two weeks if therapy is suboptimal (which can be less than 90 percent adherence). Conversely, patients who adhere to therapy can obtain continued viral suppression for many years without the need for second- or third-line options. Patients in resource-limited countries are likely to be subjected to a number of influences that challenge their ability to adhere to the prescribed therapy, including limited education and the consequent poorer understanding of their disease state, unstable housing and financial circumstances, a limited number of treatment options, and clinicians with limited antiretroviral therapy treatment experience (Kitahata and others 1996)." Jamison et al. 2006, Pg 358.
• 7. "Taking antiretroviral drugs for HIV will not cure your infection. But it may allow you to stay healthy for a long time." WebMD, "HIV: Taking Antiretroviral Drugs."
• 8. "The effectiveness of antiretrovirals depends on not only the benefits conferred, but also the associated side effects, the toxicity level of the drugs, and the patients' adherence to the drug regimen. The ability of care providers to detect incipient toxicity at an early stage also influences the magnitude of side effects and toxicities. In low-income settings with limited laboratory capacity, a greater proportion of side effects will not be detected until they become severe." Jamison et al. 2006, Pg 357.
• 9. "Laboratory monitoring determines when antiretroviral therapy should be initiated and when it should be changed because of toxicity, lack of efficacy, or resistance. The optimal frequency and precision of monitoring depends on numerous factors." Jamison et al. 2006, Pg 358-9.
• 10. Rutherford, Sangani and Kennedy, 2000, Abstract.
• 11.
• Antiretroviral Therapy Cohort Collaboration 2008, Pg 294, Table 2.
• "Potential years of life lost (PYLL) were calculated as the sum of years that HIV-positive participants in our analyses lost because of premature death. PYLL is calculated with death before the age of 65 years being considered premature, since this is deemed to be the age at which most people retire. PYLL were expressed as per 1000 person-years from age 20 to 64 years." Antiretroviral Therapy Cohort Collaboration 2008, Pg 295.
• 12. Antiretroviral Therapy Cohort Collaboration 2008, Pg 296, Table 4.
• 13. See Centers for Disease Control and Prevention, "Effect of Antiretroviral Therapy on Risk of Sexual Transmission of HIV Infection and Superinfection."
• 14. Jamison et al. 2006, Pg 332.
• 15.
• Gates Foundation, "Working with Botswana to confront the AIDS crisis."
• AVERT, "HIV & AIDS in Botswana."
• 16. "Initiating antiretroviral therapy can also have detrimental effects by causing complications from latent or undiagnosed opportunistic infections, especially in resource-poor settings." Jamison et al. 2006, Pg 354.
• 17. "It is well documented that initiating antiretroviral therapy in severely immunosuppressed patients can result in illnesses associated with reconstitution of the immune system (Shelburne and others 2005)." Jamison et al. 2006, Pgs 354-5.
• 18. "Long-term toxicities related to treatment may include atherosclerosis, lipodystrophy, hepatic failure, and cardiac failure. Researchers are still evaluating the effects of these toxicities on HIV/AIDS mortality." Jamison et al. 2006, Pg 355.
• 19. "Studies in India, Mexico, Senegal, and Uganda point to poor adherence (which for some classes of drugs can be adherence of less than 95 percent), inadequate doses and regimes, and poor monitoring as factors that contribute to more rapid development of antiretroviral therapy resistance (Oyugi and Bangsberg 2004, Laniece and others 2004, Bautista and others 2003, Liechty and Bangsberg 2003). By contrast, experiences in Haiti and Uganda suggest that it is possible to achieve adherence rates in developing countries equal to or better than those observed in high-income countries (Farmer and others 2001; Mitty and others 2002)." Jamison et al. 2006, Pg 358.
• 20. "In recent years, the most volatile parameter in cost-effectiveness analyses for HIV/AIDS has been the prices of antiretroviral drugs, which have dropped by about two orders of magnitude for some LMICs. Price reductions have not been consistent across countries, nor have they necessarily been larger for the poorest countries. This variability in pricing greatly complicates the establishment of national guidelines regarding which regimens to prescribe under which circumstances, because the ranking of regimens varies among and within countries as relative prices change." Jamison et al. 2006, Pg 357.
• 21. "In 2008, the overall median price of commonly used drug regimens for all countries with Global Fund programs was US$188 (IQR: US$ 171 – $US 209). The median price increased with national income level." Global Fund, "Innovation and Impact (2010)," Pg 70. • 22. "Based on these estimates, in 2008, the overall median cost of providing first-line ART for Global Fund programs was around US$ 588 per patient-year (IQR: US$571 – US$ 609): US$526 in low-income countries, US$ 645 in lower-middle income countries and US\$ 740 in upper-middle income countries." Global Fund, "Innovation and Impact (2010)," Pg 70.
• 23. See the summary of Global Fund-supported programs starting on Global Fund, "Innovation and Impact (2010)," Pg 106 for a sense of the scope of the Global Fund's project portfolio.
• 24. "CHAI's Access Programs have worked with generic pharmaceutical companies to negotiate affordable prices for HIV/AIDS medicine. Since 2003, CHAI has completed pricing agreements for 40 formulations of antiretrovirals (ARVs) with eight companies. Currently, more than 70 countries have access to reduced pricing for these medicines." William J. Clinton Foundation, "Access Programs."
• 25. William J. Clinton Foundation, "Annual Report (2007)," Pg 14. See William J. Clinton Foundation, "Antiretroviral Price List (2009)" for a complete list of drug prices as of August 2009. A more recent list may be available at http://www.clintonfoundation.org/what-we-do/clinton-hiv-aids-initiative/information-center-resources. Context on first- vs. second-line drugs: "Studies from high-income countries have unequivocally demonstrated that the probability that an antiretroviral therapy regimen will achieve viral suppression diminishes with each subsequent regimen (Deeks and others 1999) ... Thus, the expected survival benefit per month of antiretroviral therapy declines with each change of regimen. In contrast, the monthly cost of therapy rises as a patient moves from first-line to more expensive protease inhibitor–based second-line and subsequent therapies. Given this steadily declining cost-effectiveness, wealthier countries are likely to offer a greater number of regimen changes than poorer countries." Jamison et al. 2006, Pg 358.
• 26. Jamison et al. 2006, Pg 62, Table 2.B.1.
• 27. A year spent with AIDS is equated with 0.505 DALYs, while a year spent with an HIV infection that has not progressed to AIDS is equated with 0.135 DALYs (see official disability weights at Lopez et al. 2006, Pg 119). World Health Organization 2008 implies that a year of someone with AIDS receiving ART can be equated to a year with HIV that has not progressed to AIDS: "The disability weight for AIDS cases receiving antiretroviral therapy was set to be the same as that for HIV cases, apart from the terminal stage assumed to be have the same duration and disability weight as AIDS cases not receiving antiretroviral therapy." For simplicity, we assume that ART is always used to treat people with AIDS and affects their quality of life such that it is equivalent to having non-advanced HIV (this assumption is generous to the ART intervention in cost-effectiveness terms, since in fact ART may often be used to treat earlier-stage HIV and may not translate cleanly from one year of treatment to one year of full-blown AIDS averted). We thus equated each year on ART with 0.37 DALYs (0.505 - 0.135).