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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities 4 Principles of Scale-up Much has been learned from both developed and developing nations that have accomplished large-scale antitretroviral therapy (ART), and it is now clear that effective scale-up is a realistic objective in many settings. Before this can happen, however, the stigma and discrimination that can hamper efforts to curb the global HIV/AIDS pandemic must be addressed. To initiate the scale-up process, countries will have to identify those needing treatment, as well as the various possible points of entry into treatment programs. Once persons in need have been identified, scale-up efforts should be guided by a core set of principles. The many lessons learned from previous country efforts (see Chapter 3) have allowed the World Health Organization (WHO) to formulate a set of such guidelines that countries may wish to use as a template for beginning scale-up. These guidelines include strategies for diagnosing HIV and AIDS, deciding when to initiate therapy, determining which regimen to use given the characteristics of the population needing treatment, and deciding when and how to monitor therapy. While these strategies can serve as a useful guide, however, treatment providers must remain cognizant of the limitations associated with their particular setting. Resource-constrained settings are beset by other health problems, such as tuberculosis (TB) and malnutrition—both of which will affect the opportunities and challenges faced during scale-up. Additionally, the success of any ART program will depend upon many factors, crucial among which is adherence to therapy. The many lessons learned about adherence from past experience with ART (see Chapter 3) can be applied
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities during the initiation and implementation of treatment programs in resourceconstrained settings. Finally, the integration of prevention and treatment is essential, as is palliative care for AIDS patients in developing countries. REDUCING STIGMA AND DISCRIMINATION Stigma and discrimination, often driven by fear, can undermine efforts to treat and care for persons with HIV/AIDS. With HIV/AIDS, fear of illness, contagion, and death can affect not only patients themselves, but also those living with and caring for them, such as family members, co-workers, and health care workers. In addition to the stigma associated with the infection and the disease itself, persons with HIV/AIDS may face the stigma associated with belonging to a specific group, such as homosexuals, prostitutes, injection drug users, or persons engaging in “casual” sex. Stigma can result in silence, denial, ostracism, and violence. Clearly, these reactions can impact interest in and ability to seek diagnosis and care for HIV/AIDS. Stigma and discrimination can discourage people from finding out about and revealing their HIV status, which in turn can affect prevention and treatment efforts. In Africa, 90 percent of HIVinfected people still do not know of their status (Harries et al., 2002); fear of stigma could be one reason for this. Stigma also can affect the quality of care received by people diagnosed with HIV/AIDS. A survey of 1,000 Nigerian physicians, nurses, and midwives, for example, assessed the prevalence of stigma and discrimination (UNAIDS, 2003a). Fully 10 percent of providers admitted to having refused care or denied admission to a hospital for a patient with HIV/AIDS. Almost 40 percent of those interviewed believed that a person’s appearance revealed his or her HIV-positive status, while 20 percent believed that people with HIV/AIDS had behaved immorally and deserved their fate. Factors contributing to these attitudes and behaviors included a lack of knowledge about the virus; a lack of protective equipment, prompting fear among health care providers of acquiring the infection from patients; and frustration at not having medications to treat HIV/AIDS patients, who therefore were “doomed” to die. Strategies to reduce stigma may include providing information, counseling, imparting coping skills, and promoting social interaction with persons living with HIV/AIDS. It is possible that providing treatment for HIV/ AIDS may decrease stigma by restoring health, which in turn will allow those infected to live symptom-free and engage in work and community activities, and by reducing fear of contagion and death. By providing hope to people living with HIV/AIDS, the widespread availability of ART may reduce the stigma associated with seeking testing and treatment. Unfortunately, the literature documenting effective methods for reducing the stigma associated with HIV/AIDS in resource-poor settings needs to
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities be strengthened considerably. Referring to health-related stigma in developing countries in general, the Fogarty International Center of the National Institutes of Health (NIH) has written: “Little is known about the pervasiveness of stigma in the developing world and how healthcare systems can tackle its negative consequences. Effective action has been slow in coming, in part because of the continuing gaps in knowledge” (NIH, 2003). In recognition of this lack of knowledge, in 2002 NIH launched a Stigma and Global Health Research Program. The first 19 awards under the program were announced in October 2003; expected 5-year funding for the program is approximately $16.5 million (NIH, 2003). The NIH grant recipients will establish a global network of researchers to “develop the field of stigma and global health research by testing hypotheses and generating data on the etiology of stigma and effective interventions for its negative effects on health” (NIH, 2003). The network will help identify best practices, opportunities, and obstacles in research on stigma related to global health. Through the studies conducted by this network and others, culture-specific interventions to reduce stigma, perhaps tailored to different demographic groups, should be tried and evaluated. In June 2001, the United Nations General Assembly Special Session on HIV/AIDS issued a Declaration on Commitment on HIV/AIDS. This declaration included a provision for UN Member States to “develop strategies to combat stigma and social exclusion connected with the epidemic” and “enact, strengthen or enforce, as appropriate, legislation, regulations and other measures to eliminate all forms of discrimination against . . . people living with HIV/AIDS…” (UNAIDS, 2003a). According to a UNAIDS report in 2003, almost half of all African countries had adopted no legislation to prevent discrimination against people living with HIV/AIDS (UNAIDS, 2003b). Recommendation 4-1. Governmental and community leaders at all levels of civic life should spearhead an effort to create a culture of openness and support in order to eliminate stigma and ensure the successful continuance of antiretroviral treatment and HIV prevention programs. IDENTIFYING POINTS OF ENTRY Identifying persons in immediate need of treatment provides one challenge for the efficient and effective scale-up of ART. As noted earlier, there are multiple possible points of entry for treatment programs, each of which may target different sectors of the population and initially identify infected persons at different stages of the disease. Early detection and counseling to prevent subsequent transmission, with regular follow-up, are desirable even though patients initially entering
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities care at a later stage of infection are more likely to be immediately clinically eligible to begin ART under the WHO guidelines endorsed by the committee. The former patients also may be more likely to remain in care. At the same time, the challenges of beginning care and treatment for those in the latest stages of disease include reconstituting a highly suppressed immune system and the necessity of treating opportunistic infections, such as TB. For these and other reasons, mortality may be higher for patients entering care at later disease stages, as was the case for patients enrolled in treatment programs in Haiti (Fitzgerald, 2004) (see Chapter 3). Existing health care facilities—already providing services for other health needs—may take on HIV/AIDS testing and treatment as scale-up unrolls. The screening of military personnel and other occupational groups can also serve as entry points for ART. Three additional points of entry may be considered during scale-up: voluntary counseling and testing centers, mother-to-child transmission prevention programs, and TB treatment and control programs. Voluntary Counseling and Testing Programs Only 5–7 percent of people in most developing countries know their HIV status (WHO, 2003a). Clearly then, counseling and testing must precede ART and HIV/AIDS care. At the same time, voluntary counseling and testing (VCT) centers established to provide these services offer the opportunity to address a comprehensive range of measures for HIV/AIDS prevention, treatment, and care. Though the majority of apparently healthy persons seeking to know their status can be diagnosed most effectively in VCT programs, some asymptomatic persons will be found HIV-positive through other mechanisms, such as blood bank screening. Such patients should still be referred to VCT programs to ensure that preventive counseling is provided in conjunction with entry into ART programs. Requiring that capable HIV-positive patients obtain VCT clinic counseling prior to receipt of ARVs may encourage disclosure and foster the linkage of treatment, prevention, and care. Counseling and testing involve risk evaluation, facilitated decision making following testing, and education about preventive measures for those found to be HIV-negative or -positive. UNAIDS has identified several critical elements of counseling and testing programs: testing should be voluntary; results should be kept confidential; counseling should focus on the individual client’s needs; HIV-positive and -negative persons should be referred for ongoing support; and stigma-reducing activities should be incorporated into the services provided (CDC, 2004; UNAIDS, 2000). Centers offering VCT services can serve as an important link to medical and
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities support programs that provide treatment and care for those eligible to receive ART. Same-day testing sites can facilitate this linkage. Mother-to-Child Transmission Prevention Programs Pregnancy can provide an opportune point of entry for women who might not otherwise seek health care for themselves. In addition, antenatal clinics are used to collect data for HIV prevalence estimates (UNAIDS, 2003a). In the history of treating and caring for those with HIV/AIDS, special attention has focused on preventing transmission of the virus from mother to child. Mother-to-child-transmission (MTCT) prevention programs have been established to provide specialized services to women during their pregnancy and then to the children they bear during the immediate postpartum period. While MTCT prevention programs can provide an opportunity for women to enter health care, in some regions of resource-poor settings only 1 percent of women have access to these services. Moreover, partner opposition can reduce the likelihood of participating in these programs. Building on the success of these programs, the Maternal-to-Child-Transmission-Plus (MTCT-Plus) Initiative was established in 2002 (Columbia University Mailman School of Public Health, 2004). The goal of this initiative is to provide specialized care, including ART, to HIV-infected women during and following pregnancy, to their children, and to their partners. The program’s comprehensive reach provides an opportunity for family members to enter a system of care and for mothers to receive continued care following childbirth. The MTCT-Plus Initiative is coordinated by the Mailman School of Public Health at Columbia University and is funded by private foundations and the U.S. Agency for International Development (USAID). The programs operate in 12 sites ranging from rural clinics to teaching hospitals—11 in sub-Saharan Africa and 1 in Thailand. The comprehensive HIV/AIDS care provided includes ART, therapy for the prevention and treatment of opportunistic infections, TB prevention services, nutrition support, family planning, and supportive services. Recognizing that HIV/AIDS has psychosocial as well as clinical dimensions, the programs use multidisciplinary teams of providers and supporters that include nurses, counselors, and pediatric and adult physicians. As of November 2003, 2,000 people had been enrolled in MTCT-Plus programs. Women can enroll in the programs either during or following pregnancy; currently, 40 percent are enrolled antepartum and 60 percent postpartum. In recognition of the fact that HIV/AIDS affects families, not just individuals at risk for or with HIV/AIDS, and that family-based endeavors may improve overall treatment and care, enrollment is offered to
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities other members of the household as well. Of the 2,000 people enrolled as of November 2003, one-third were children, and one-fifth were partners of the (index) women. The programs target people at the earlier stages of disease. The mean CD4 count of patients beginning treatment is 379. The index women are at a less advanced stage of disease than their partners who become enrolled. Most of the infants enrolled in the program are of indeterminate status; they are followed clinically as an effort to provide comprehensive family care. Each MTCT-Plus site uses standardized protocols with respect to treatment eligibility criteria, treatment monitoring, toxicity management, drug regimens, and pediatric dosing. An attempt is made to harmonize these protocols with both country-specific and WHO guidelines. The antiretrovirals (ARVs) used in these programs are procured by UNICEF; approximately half are generic products. CLINICAL PRINCIPLES Because of the complexity of HIV and AIDS, WHO established clinical guidelines in 2003 as part of its 3-by-5 campaign (see Chapter 2) to assist programs in scale-up of ART (WHO, 2003b). These guidelines take into account experience gained in the clinical management of HIV/AIDS in the developed world and lessons learned from treating the disease in the developing world. Data from clinical trials and observational studies underlie the guidelines. In recognition of the limitations faced by resource-constrained settings, such as cost and availability of drugs and diagnostics, the WHO guidelines offer suggestions specific to these settings. The guidelines provide a framework that can be used to standardize and simplify treatment for this complex disease and encompasses the point at which to start therapy; first- and second-line combination regimens; considerations involved in treating subgroups of patients, such as those coinfected with TB, pregnant women, and children; means of monitoring therapy; and indicators for changing regimens. As noted earlier, these recommendations are based on scientific and clinical experience and evidence, drug availability and cost, the requirement to refrigerate some ARVs, the need for and availability of laboratory monitoring, drug toxicity profiles, and the risk of drug interactions. The guidelines acknowledge limitations in areas in urgent need of research, such as the treatment of pregnant women and individuals coinfected with TB. Nonetheless, they provide a critically important starting point by outlining simple criteria and steps that can be used in even the most resource-poor settings. The WHO guidelines can be used by providers with a range of experience in diagnosing and treating people with HIV/AIDS. The simplified,
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities standardized guidance they offer can be indispensable given that many ART scale-up programs in resource-limited settings need to rely on community involvement and the recruitment of unskilled workers or health care professionals with little or no experience in managing such programs. At the same time, however, HIV/AIDS experts warn that these guidelines should not be considered a substitute for local program manuals. Nor should they be used to underestimate the complex nature of ART, the need for context-specific individualized care, and the reality that early treatment decisions can profoundly alter the course of disease and limit a patient’s response to future therapy in the case of first-line failure. Recommendation 4-2. Before countries develop their own directives, the World Health Organization’s 2003 guidelines for the treatment of adults, children, and pregnant women should serve as an initial template for the design of antiretroviral therapy programs with respect to when to start therapy, which regimens to use, how to monitor the progress of therapy, and when to switch drugs or terminate therapy. As new evidence becomes available, through the efforts of international, national, and local research, the WHO guidelines, particularly with regard to pregnant women and those coinfected with tuberculosis, may require refinement or modification. One clinical principle that deserves mention is that because therapy for HIV/AIDS is an ongoing process, an adequate longitudinal medical record is an essential tool in patient management. In many developing countries, medical records systems will need significant improvement, especially where those records are currently held by the patient or where documentation is organized around discrete visits rather than continuity of care. Relevant training in longitudinal medical record keeping and changes in patient flow through the clinic should be considered, where needed, to facilitate this process. The remainder of this section reviews in turn considerations involved in using the laboratory to diagnose, initiate, and monitor ART; selecting a treatment regimen; treating dual epidemics of HIV and TB; treating women; treating pregnant women; treating children; and addressing the role of nutrition in HIV/AIDS and its treatment. Using the Laboratory to Diagnose, Initiate, and Monitor ART In the developed world, laboratory and clinical criteria weigh heavily in the initiation and monitoring of ART. Cost and infrastructure needs may limit the ability of resource-constrained settings to use such a laboratory-intensive approach for treating patients with HIV/AIDS.
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities In the developed world, standard tests administered prior to beginning therapy include a test to detect HIV, followed by a confirmatory test; a test to determine CD4 T cell count—a marker of immune function and disease stage; and a test to determine the amount of virus present in the blood (viral RNA or viral load)—a marker of disease burden. The WHO guidelines do recommend baseline HIV testing and, when possible, CD4 T cell count (or the surrogate marker, total lymphocyte count [TLC]) prior to initiation of therapy (see Appendix B, Table A). While a confirmatory test to diagnose HIV is preferable, if a second test (e.g., rapid antibody test, Western Blot) is not available, therapy should proceed based on clinical criteria defining AIDS stage (see Appendixes B and E). In the developed world, CD4 T cell count and viral RNA load are assessed throughout therapy to monitor progress and determine the success of the therapeutic regimen. When laboratory tests such as CD4 T cell count and viral load are not available, the WHO guidelines recommend the use of clinical criteria for symptomatic appraisals to ensure that therapy can be monitored in settings without sophisticated laboratory capacity or personnel. Finally, because of potential side effects and toxicities of ARVs—and the progression of HIV infection—additional baseline laboratory tests obtained in less resource-constrained countries include determinations of red blood cell count, renal function, liver enzymes and function, and lipid status (U.S. Department of Health and Human Services, 2003). WHO recommends additional tests such as these when infrastructure allows (see Appendix B, Table E). Laboratory testing can be costly and require sophisticated laboratory infrastructure and trained technicians. A CD4 T cell count is typically determined using a flow cytometer for measurement and is costly. Of note, there are no data indicating what degree of CD4 or viral load testing translates into cost-effective clinical or public health benefits. For example, in the United States, no trial has been conducted to compare clinical end-points between patients who received viral load testing and those who did not. Less-expensive technologies and surrogate laboratory markers are available and have been used in the developing world to monitor therapy. While a flow cytometer is commonly used to quantify CD4 T cell count and assess disease stage and progression, some countries have used alternative technologies to garner this information. A West African study, for example, demonstrated the utility of Dynabeads, a low-cost alternative to the flow cytometer based on epifluorescent microscopy (Diagbouga et al., 2003). The cost of an epifluorescent microscope is approximately half that of the least-expensive flow cytometry equipment, and the reagent cost per assay is only 12 percent of the cost of the assay for a CD4 T cell count (Diagbouga
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities et al., 2003). Another technology, the Cytosphere bead assay, is reportedly easier to use but more expensive (US$8/test, compared with $3–5/ Dynabead test, as of December 2002). Even these alternative technologies, however, are limited by the need for trained technicians, an element of subjective interpretation, the need for refrigeration and a reliable power source, and fatigue associated with the manual nature of the technology. Because of these concerns and limited formal evaluation, WHO has recommended that both methods be evaluated in a multicenter study before being officially recommended to laboratories in the developing world. As noted, TLC has been suggested as a surrogate for CD4 T cell count; indeed, it is recommended by WHO. Since the CD4 T cell is one type of lymphocyte, CD4 T cell count correlates with TLC. A number of reports have shown TLC to be a useful predictor of significant immunosuppression, as measured by a CD4 cell count of less than 200/µL in HIV-infected persons. If TLC were used to determine who was eligible to start therapy, a lower level would increase specificity (by increasing the likelihood that people with high CD4 counts would not be incorrectly targeted for therapy) but decrease sensitivity (by increasing the likelihood that people with low CD4 counts would not be identified). The cost of laboratory tests is only one of many costs associated with laboratory monitoring of HIV/AIDS patients. The procurement and proper use of assays and reagents depend on an enormous amount of infrastructure, which may include data management programs; laboratory equipment and supplies (e.g., refrigerators, freezers, centrifuges, thermocyclers, and pipettes); proficiency testing programs; laboratory accrediting agencies, and skilled technicians. At an even more basic level, effective laboratory monitoring relies on a range of nonlaboratory resources that are taken for granted in resource-rich countries, such as reagent-grade water, electrical power, and theft prevention measures. Securing infrastructure and resources can be very costly and is particularly important given that theft is a large problem in many resource-constrained settings. It may be particularly challenging to obtain and maintain these resources in rural areas of resource-constrained settings, where infrastructure may be even weaker. Recognizing the infrastructure costs and limitations in resource-constrained settings, WHO has set forth guidelines for conducting laboratory testing prior to initiating therapy, for monitoring therapy, and for defining treatment failure (see Box 4-1). The WHO recommendations are tiered for primary health centers, district hospitals, and regional referral hospitals. Recommendation 4-3. Donors and program managers should plan and budget for laboratory activities that will foster more accurate and effective HIV diagnosis and management, using the World Health Organization’s 2003 guidelines as the initial template. Incorporating
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities BOX 4-1 WHO Guidelines for the Initiation of Antiretroviral Therapy in Adults and Adolescents If CD4 Testing Is Available: For persons with WHO Stage IV disease, therapy should begin regardless of CD4 count. For persons with WHO Stage III disease, therapy should begin with consideration of using CD4 cell count < 350 /mm3. For persons with WHO Stage I or II disease, therapy should begin with CD4 cell counts ≤ 200/mm3. If CD4 Testing Is Not Available: For persons with WHO Stage IV disease, therapy should begin regardless of total lymphocyte count. For persons with WHO Stage III disease, therapy should begin regardless of total lymphocyte count. For persons with WHO Stage II disease, therapy should begin with a total lymphocyte count ≤ 1200/mm3.* * A total lymphocyte count = 1200/mm3 can be substituted for the CD4 count when the latter is unavailable and HIV-related symptoms (Stage II and III) exist. It is not useful in the asymptomatic patient. Thus, in the absence of CD4 cell testing, asymptomatic HIV-infected patients (Stage I) should not be treated because there is currently no other reliable marker available in severely resource-constrained settings. SOURCE: WHO, 2003b. emerging evidence and resources into their decision-making process, countries should consider developing population-specific guidelines reflective of the best possible practices in their particular circumstances. In those localities where it is possible to go beyond the WHO guidelines, treatment failure should be defined through viral RNA determination; otherwise, it should be defined by means of clinical or other laboratory markers consistent with the guidelines. Recommendation 4-4. Under the leadership of their ministries of health and national reference laboratory experts, all countries should develop hierarchical laboratory networks that integrate the local, district, and referral hospital levels through tiered quality assurance programs and provide referral support for increasingly complex laboratory assays. Full development of these networks is not required before the initiation of scaled-up antiretroviral therapy programs, however. National reference laboratories should promulgate tier-specific quality assurance protocols, and donors supporting ART programs should provide the means
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities to properly ensure acceptable technical performance by these laboratory networks. Dedicated funds, training, and other resources to ensure the maintenance of laboratory equipment employed in these networks should be provided. To better facilitate the diagnosis and treatment of HIV infection in infants less than 18 months of age, the laboratory networks should put in place a capacity for the direct detection of HIV, such as HIV DNA, HIV RNA, or HIV p24 antigen. Clinical criteria for monitoring treatment progress have been used in developing countries. While there are many reasons during both health and disease for weight gain or loss, patient weight has been one clinical marker used in developing countries to judge the success of ART. In the event that clinical criteria are used for treatment monitoring, however, it must be recognized that such criteria do not always provide an accurate assessment of viral suppression, and even patients who appear to be doing well may fail in their regimen if viral suppression is not above a certain threshold. Initial treatment regimens should be selected based on this awareness. The degree to which laboratory services for toxicity monitoring are used also requires special consideration in resource-constrained settings with limited infrastructure. The necessity for laboratory monitoring may be tailored to the use of certain ARVs. For example, when nevirapine is used in combination with other drugs, hepatoxicity testing may be important, whereas when zidovudine is used, a hemoglobin determination for anemia might be considered. Selecting a Treatment Regimen In the developed world, regimen selection is quite intricate because of the availability of numerous drugs and the infrastructure needed to deliver and monitor therapy, the affordability of drugs (through third-party payers in some cases), and the ability to tailor regimens to virus susceptibility. Because resource-constrained settings may not have these advantages, WHO has recommended four first-line regimens for HIV/AIDS treatment. These regimens, summarized in Table 4-1, take into account toxicities, appropriateness for use in TB-coinfected patients and in pregnant women, availability as a fixed-dose combination (FDC) (see Box 4-2), cost, and laboratory monitoring requirements. Regimen design also must take into account the population being treated with respect to age, gender, pregnancy status, and comorbid infections. According to the WHO guidelines, ARV regimens that have been shown scientifically to be ineffective or less effective than other available regimens should not be used. Specifically, mono- or dual-therapy regimens and nucleoside-only regimens should be avoided. According to a recent
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities RNA viral load level was significantly higher among HIV-1–positive subjects whose partners had seroconverted than among those whose partners had not seroconverted (90,254 copies per milliliter vs. 38,029 copies per milliliter, p = 0.01). Reflecting the population benefits of suppressed viral replication, no instances of transmission were noted from the 51 HIVinfected partners with less than 1,500 copies per milliliter. Overall in this community, however, transmission was substantial, with 90 of 415 initially seronegative partners seroconverting (11.8 per 100 person-years) (Quinn et al., 2000). Modeling studies also suggest that suppression of viral load in a high proportion of infected people can significantly reduce transmission in a population (Blower et al., 2000, 2003a, 2004). While treatment for HIV/AIDS could positively impact the prevention of new cases by decreasing viral load and reducing the infectiousness of those already afflicted with the disease, past experience with the introduction of treatment in the developed world has highlighted the potential for an increase in behaviors linked to HIV/AIDS transmission (Blower and Farmer, 2003; Blower et al., 2000, 2001). Substantial decreases in HIV mortality in the United States and other developed countries have been accompanied by a resurgence of HIV infection rates among some communities of gay men in these countries (Katz et al., 2002; Miller et al., 2000). An observational study of adults—mainly homosexual men—with AIDS in the era of HAART found an increase in sexually transmitted infections over a 4-year period in the late 1990s. A survey of 54 homosexual men found that 26 percent felt “less concerned about becoming HIV-positive” with the availability of ART. This increase in risky behavior following receipt of ART in the developed world has not been documented for other risk groups (e.g., intravenous drug abusers, heterosexuals). Factors that could contribute to this increase in risk behaviors, also called “disinhibition,” include a greater sense of security from knowing that therapy is available and improved health, leading to more or resumption of higher-risk sexual activities. Another concern is that the increase in life expectancy that can be brought about by ART affords a greater opportunity for HIV-positive persons to infect others (although as noted, treated patients should have decreased HIV viral load burdens and thus be less infectious). Modeling has been used to predict the interactions between use of ART and risk behaviors and the subsequent effect on HIV prevalence. Given otherwise optimal ART scale-up conditions (i.e., use of potent regimens that completely suppress viral replication, near-perfect adherence, and widespread use), but absent efforts to prevent increased risk behaviors, the potential benefits of increased ARV usage could be masked by increased transmission resulting from such behaviors, as was seen in the gay community in the United States (Blower and Farmer, 2003; Blower et al., 2000, 2003a,b, 2004; Velasco-Hernandez et al., 2002). Evidence from both em-
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities pirical and modeling studies, then, demonstrates that HIV prevention activities must be strengthened and integrated into ART scale-up programs if success in combating the pandemic is to be achieved. PALLIATIVE CARE FOR AIDS PATIENTS IN DEVELOPING COUNTRIES Despite advances in the treatment of AIDS patients and the potential for adding even decades of additional quality life to what might have been the case without ARVs, many of these persons will eventually face death due to the infection. Thus a humane approach to this disease includes steadfast care not only while the patient is responsive to ARVs, but also when all that can be offered is palliative care. Comprehensive national programs to care for patients with HIV/AIDS should address the needs of those who are in the terminal stage of AIDS. WHO defines palliative care as care that: Provides relief from pain and other distressing symptoms. Affirms life and regards dying as a normal process. Intends neither to hasten nor to postpone death. Integrates the psychological and spiritual aspects of patient care. Offers a support system to help patients live as actively as possible until death. Offers a support system to help the family cope during the patient’s illness and in its own bereavement. Uses a team approach to address the needs of patients and its families, including bereavement counseling, if indicated. Enhances quality of life and may also positively influence the course of illness. Is applicable early in the course of illness in conjunction with other therapies intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications. There are particular challenges to palliative care in developing countries. Palliative care of terminal AIDS patients often centers on pain management. A Ugandan study found that more than half of terminally ill patients cited pain as their chief problem (Kikule, 2003). Morphine and other analgesic opioids are inexpensive, though tight regulations hinder their availability in developing countries (Carlisle, 2003). Table 4-3, based on 2001 figures for per capita morphine consumption in African countries heavily affected by HIV/AIDS, highlights this problem. According to David Joranson of the Pain and Policy Studies Group, University of Wisconsin/
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities TABLE 4-3 Per Capita Consumption of Morphine, 2001 Country Per Capita Consumption (mg) Global mean 5.9 Africa regional mean 0.5 South Africa 3.7 Namibia 2.5 Botswana 1.7 Uganda 0.1 Tanzania 0.09 Zambia 0.03 Rwanda 0.01 Mozambique 0.01 Kenya 0.003 Cote d’Ivoire 0.002 Ethiopia 0.0002 Nigeria, Haiti, and Guyana NAa Global mean 5.9 aNA = not available. These countries did not report for 2001. NOTE: 2001 consumption is estimated with 2000 United Nations Population Data. SOURCE: David Joranson, Pain and Policy Studies Group, University of Wisconsin/WHO Collaborating Center, using 2003 International Narcotics Control Board and United Nations Demographic Yearbook, 2000. WHO Collaborating Center, the 14 countries originally selected for PEPFAR accounted for only 0.8 percent of the world’s morphine consumption in 2001 (personal communication to Hellen Gelband). Joranson further notes: All of the 14 governments are parties to the United Nation’s Single Convention on Narcotic Drugs, 1961, but it is clear from the consumption statistics that there has been little effort aimed at ensuring the availability of opioids which is a treaty obligation. This may be due to many reasons, or barriers, involving pain relief being a low healthcare priority in cancer and AIDS, lack of infrastructure to deliver medical care and pain relief, lack of medical demand (prescriptions) for opioids, inadequate education of physicians, general misunderstanding and fear of morphine, and lack of governmental action. It has been reported that patients in India have significant difficulty receiving morphine because of government fears of its diversion for nonmedical use (Ghooi and Ghooi, 2003). Culture-specific palliative guidelines are rare, though some research has been done. A recent study to determine the palliative needs of Ugandans concluded that a “good death” occurs
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities when patients are at home, free from pain, and without stigma, and do not feel dependent on others for their basic needs (Kikule, 2003). WHO’s Program on Cancer Control and Departments of Care for HIV-AIDS are currently enganged in an intitiative to enhance palliative care in southern Africa. The principal objectives are as follows (WHO, 2004b): To develop/reinforce palliative care programs with a public health approach in response to the needs and gaps identified, considering: A holistic approach to palliative care, giving special emphasis to pain relief. A systemic approach to program implementation that considers policy development, provision of care, drug availability, training, and education in the context of HIV/AIDS and cancer health problems. Integration with the existing health system at all levels of care, with special emphasis on home-based care. A team approach at the organizational and care levels. The elements of good quality performance, including improving access, acceptability, efficiency, and effectiveness. To advocate for drug availability and policy development among the governments of the participating countries. To develop a network among the participating countries that will: Promote the exchange of information and collaboration. Advocate for the integration of such programs into national strategic plans for health and social services. WHO Staging System for HIV Infection and Disease in Adults and Adolescents1 Stage I Asymptomatic Generalized lymphadenopathy Performance scale 1: asymptomatic, normal activity Stage II Weight loss, < 10% of body weight Minor mucocutaneous manifestations (seborrheic dermatitis, prurigo, fungal nail infections, recurrent oral ulcerations, angular cheilitis) Herpes zoster within the last 5 years Recurrent upper respiratory tract infections (e.g., bacterial sinusitis) And/or performance scale 2: symptomatic, normal activity
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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities Stage III Weight loss, > 10% of body weight Unexplained chronic diarrhea, > 1 month Unexplained prolonged fever (intermittent or constant) > 1 month Oral candidiasis Oral hairy leucoplakia Pulmonary tuberculosis Severe bacterial infections (i.e., pneumonia, pyomyositis) And/or performance scale 3: bedridden < 50% of the day during the last month Stage IV HIV wasting syndrome Pneumocystis carinii pneumonia Toxoplasmosis of the brain Cryptosporidiosis with diarrhea > 1 month Cryptococcosis, extrapulmonary Cytomegalovirus disease of an organ other than liver, spleen, or lymph nodes (i.e., retinitis) Herpes simplex virus infection, mucocutaneous (> 1 month) or visceral Progressive multifocal leucoencephalopathy Any disseminated endemic mycosis Candidiasis of esophagus, trachea, bronchi Atypical mycobacterioris, disseminated or lungs Nontyphoid salmonella septicemia Extrapulmonary tuberculosis Lymphoma Kaposi’s sarcoma HIV encephalopathy And/or performance scale 4: bedridden > 50% of the day during the last month 1 Appendix B. WHO Staging System for HIV Infection and Disease in Adults and Adolescents. Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach. 2003 Revision. World Health Organization 2003. REFERENCES Allen S, Meinzen-Derr J, Kautzman M, Zulu I, Trask S, Fideli U, Musonda R, Kasolo F, Gau F, Haworth A. 2003. Sexual behavior of HIV discordant couples after HIV counseling and testing. AIDS 17(5):733–740. Bartlett JA, DeMasi R, Quinn J, Moxham C, Rouseau F. 2001. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS 15:1369–1377.
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Representative terms from entire chapter: