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Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS (2005)

Chapter: 2 Confronting HIV/AIDS on the Ground

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Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
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2
Confronting HIV/AIDS on the Ground

Pandemic: A disease affecting the majority of the population of a large region, or which is epidemic in many different parts of the world (Thomas, 1973:P-12).

In the fourteenth century, the Black Death1 ravaged Europe, killing a third of its population. In the sixteenth century, smallpox claimed the lives of approximately 17 million New World Indians and felled the great Aztec and Inca Empires. In the early twentieth century, influenza killed countless numbers in Europe, Asia, Australia, and the Americas—affecting one-quarter of the world’s population. Throughout human history, epic infectious outbreaks have occurred periodically, leaving victims of all ages, races, and economic status in their wake. Today, however, the poor bear the brunt of epidemic infections, both acute and chronic. Exacerbated by a lingering burden of malnutrition, scant or absent health services, and other risk factors, malaria, tuberculosis (TB), vaccine-preventable diseases, and simple respiratory and diarrheal ailments continue to plague the world’s neediest populations. Just a few decades ago, these diseases represented the primary unfinished agenda in global health.

That situation changed with the emergence of HIV/AIDS, the modern successor to the great pandemics of history. Twenty-five years after first being recognized in humans, the disease has now claimed more than 20

1  

A bacterial infection caused by Yersinia pestis, also known as the plague.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

million lives, and close to 40 million people worldwide harbor HIV (UNAIDS, 2004). Of the latter, 30 million are Africans, concentrated in southern and eastern Africa where HIV prevalence among adults now exceeds 15 percent in many countries and 30 percent in at least four countries (Botswana, Lesotho, Swaziland, and Zimbabwe). In less than 10 years, HIV/AIDS has reversed the gains in life expectancy achieved by Africa over 50 years and orphaned 12 million children, half of whom are between the ages of 10 and 14 (UNAIDS, 2004). Girls and women are especially vulnerable to HIV, and now account for 50 percent of people living with HIV worldwide and 57 percent of those in sub-Saharan Africa (UNAIDS, 2004).

At the same time, HIV/AIDS increasingly threatens other regions of the world. According to the National Intelligence Council, by 2010 China will likely have 10–15 million people living with HIV, India 20–25 million, and Russia 5–8 million (Morrison, 2004).

Viewed from the perspective of the wreckage of human lives, there is nothing positive about HIV/AIDS. However, unlike earlier pandemics that took place in the absence of knowledge, tools, and connectivity, today’s crisis offers one opportunity: a decisive global response. What form should this response take? Rich countries have a moral and political imperative to invest heavily in effective treatments and other material assistance to poor countries highly impacted by HIV/AIDS. Yet no amount of money can fully substitute for experienced professionals with a variety of skills assisting counterparts on the ground in fighting the epidemic.

This chapter begins by examining the linkages between HIV/AIDS and two other infectious diseases—TB and malaria—that have a major impact on the developing world, as well as the resulting health care challenges. This is followed by an overview of the impacts of HIV/AIDS at the individual, household, and societal levels. Next, the chapter provides a closer look at HIV/AIDS, itself, including its pathophysiology, transmission, and natural course, and comorbidities and cofactors in disease progression. Finally, the chapter reviews treatment and care for HIV/AIDS, addressing in turn antiretroviral therapy (ART), the problem of drug resistance, elements of a comprehensive care model for those infected in developing countries, clinical entry points for treatment and care, and issues in providing ART and HIV/AIDS care in resource-limited settings.

HIV/AIDS, TUBERCULOSIS, AND MALARIA

Linkages Among the Three Diseases

In an attempt to target high-risk individuals, health programs addressing malaria, TB, and HIV infection often focus on biologically vulnerable groups. Table 2-1 summarizes the available evidence on biological and

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

TABLE 2-1 Available Evidence on Biological and Disease-Related Vulnerability Factors

Vulnerability Factor

Malaria

Tuberculosis

HIV/AIDS

Age

Children under 5, high endemicity; all ages, low endemicity

Children under 5 and adults

Young adults

Pregnancy

Strong evidence for association

Weak evidence for association

No evidence for association

Male/Female Ratio

Equal

Children, M=F; adults M>F

Adolescents M<F; adults M=F

Genetic Influences on Infection or Disease Vulnerability

Ethnic traits, red-cell abnormalities, HLA/MHCa markers

Ethnic traits, genes for vitamin D receptor

Chemokine receptors (for example, CCR5)

Interactions

Coinfection with HIV increases degree and severity of infection

Coinfection with HIV increases disease progression

Other sexually transmitted diseases increase HIV infectiousness

aHLA/MHC = human leukocyte antigen /major histocompatibility complex.

SOURCE: Adapted from Bates and colleagues (2004).

Reprinted, with permission, from Elsevier (The Lancet Infectious Diseases 2004:268).

disease-related vulnerability factors. Depending on the disease, infants, children under age 5, girls and women, pregnant women, and people of reproductive age are particularly vulnerable to infection.

While the approach of focusing on biologically vulnerable groups is useful in planning health interventions, poverty and a lack of education and available health services all contribute to the bigger picture (Bates et al., 2004). Indeed, the World Health Organization has identified the world’s 1.2 billion people living in absolute poverty as most vulnerable to malaria, TB, and HIV infection (WHO, 2002b). High burdens of these diseases contribute to national and individual poverty, linking poverty and disease in a downward spiral. Moreover, low general educational attainment and a lack of knowledge about HIV transmission correlate with increased rates of risky behavior and HIV infection (Bates et al., 2004). HIV/AIDS and malaria also restrict opportunities for formal education: HIV/AIDS has caused reductions in school enrollment of up to 36 percent in some parts of Africa (Cohen, 1999), while malaria accounts for 10 to 50 percent of school days

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

lost to illness in sub-Saharan Africa (Sachs and Malaney, 2002). Certain occupations or livelihoods also increase the risk of acquiring HIV (e.g., female sex workers, long-distance truck drivers), malaria (e.g., rural subsistence farmers, forest workers), and TB (e.g., workers exposed to silica and other dusts).

Medical linkages among the three diseases are fairly well established, with the evidence for a link between HIV/AIDS and TB being quite compelling. TB is a leading killer of people with HIV/AIDS, and up to 80 percent of TB patients are HIV positive in countries with a high prevalence of HIV (Ruxin et al., 2005). Although not as strong, an association between HIV infection and clinical malaria has also been identified in pregnant women (Ladner et al., 2002, 2003). Additionally, antimicrobial drug resistance and treatment delays complicate all three diseases, increasing transmission, morbidity, and mortality.

Given that these three diseases are the top infectious disease killers in the world today, and given the linkages described above, some believe that investing solely in combating one disease may compromise the building of local capacities to foster broader health benefits (Tan et al., 2003). The belief is that until systems are in place to deliver essential health services on a large scale, progress against one disease will be achieved at the price of neglecting others. It is thought that lasting control of HIV, TB, and malaria will depend on strengthening health systems as well as disease-specific programs (Ruxin et al., 2005).

Current Scope

As noted in Chapter 1, close to 40 million people are currently estimated to be living with HIV/AIDS, 95 percent of them in developing countries, particularly sub-Saharan Africa. In 2004 alone, almost 5 million people are thought to have become infected with HIV, including 2 million women and 800,000 children. The estimated total number of AIDS deaths in 2004 was 3.1 million (UNAIDS, 2004).

TB, a progressive and debilitating bacterial infection caused by Mycobacterium tuberculosis and spread from person to person by coughing and sneezing, is the world’s second most common cause of death from infectious disease after HIV/AIDS, killing nearly 2 million people and causing 8 to 9 million new infections each year (Frieden et al., 2003). Of the 40 million people currently living with HIV/AIDS worldwide, one-third are coinfected with TB, most of these living in sub-Saharan Africa (WHO, 2002c). HIV/AIDS and TB are so closely connected that the term “coepidemic” or “dual epidemic” is used to describe their relationship.

Malaria, a parasitic infection transmitted by Anopheles mosquitoes, causes 1 to 2 million deaths worldwide every year, more than 90 percent of

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

which are in sub-Saharan Africa among children under 5, although adults also suffer morbidity and mortality from the disease. Malaria also threatens at least 24 million pregnancies annually and causes low birth weight, a four-fold risk factor for increased infant mortality. Malaria’s burden on health systems is immense: 30 percent of all outpatient visits and 20 to 50 percent of all hospital admissions in affected countries in Africa are attributable to the disease (WHO, 2003c). Malaria’s contribution to poverty is seen at the household level and in slowed economic growth overall. Populations living in regions of high malaria transmission in 1965 had annual economic growth rates that were 1.3 percent lower than those of other countries over the period 1965-1990 (Sachs and Malaney, 2002).

Health Care Challenges

The critical lack of human health care resources in the scale-up of HIV/ AIDS treatment and care was the central driver for this study. Several recent reviews and human resource assessments have emphasized the growing HIV-related work burden (which is also characterized by clinical and organizational complexity) juxtaposed against poor basic health services and weak human resources. To some extent, similar issues apply to TB and malaria, whose acute management and long-term control are only slightly less demanding than is the case for HIV/AIDS. TB diagnosis requires, at a minimum, high-quality sputum microscopy, and current treatment guidelines for uncomplicated infections require that patients take four drugs under direct supervision for their first 2 months of treatment, followed by two drugs for another 4 to 7 months. Effective and sustainable malaria control involves activities ranging from vector control, to intermittent preventive treatment of high-risk individuals, to epidemic forecasting. These measures are especially difficult to implement in settings of decentralized health care and shortages of skilled personnel. Malaria treatment is also complicated by growing drug resistance in most endemic countries, a situation that has led to an increase in deaths from the disease over 10 to 20 years; nonetheless, failing drugs such as chloroquine remain in widespread use, especially in sub-Saharan Africa (IOM, 2004). In 2002, the World Health Organization recommended that governments rapidly adopt more effective first-line malaria treatments, in particular, artemisinin-based combination therapies that are currently in limited global supply. Treatment of severe and complicated malaria requires a range of technically sophisticated diagnostic, therapeutic, and supportive interventions, depending on available local resources.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

The Starting Point for HIV/AIDS Care: Prevention, Education, and Awareness

Although American health professionals are proficient in many biomedical interventions and tools that can now be applied to the care of HIV/ AIDS patients in the PEPFAR focus countries, it is still critically important to acknowledge behavioral interventions as a means of stemming the global HIV/AIDS epidemic. Failure to expand access to HIV prevention while scaling up ART in developing countries could lead to a situation similar to that in the industrialized world, where HIV prevention was insufficiently emphasized as HIV treatment was expanded; the result was increases in risk behavior and infection rates (Global HIV Prevention Working Group, 2004). Experience in the few countries in which generalized epidemics have been substantially curtailed, albeit limited, suggests that adequately resourced, politically supported national prevention programs addressing the behavioral mediators of HIV can change the course of the global HIV/AIDS epidemic by averting millions of infections (Harrison and Steinberg, 2002).

The prevention message—communicated at HIV treatment sites and through mass campaigns focused especially on young people (who are not as likely as adults to visit medical settings)—needs to reach those at high risk of infection, those considered to be at low risk, and those already infected. An effective prevention plan encompasses a set of strategies that achieve maximum impact when pursued in combination (Global HIV Prevention Working Group, 2004):

  • Behavior change programs to promote condom use, reduced numbers of partners, mutual monogamy, abstinence, and delayed initiation of sexual activity

  • Prevention and treatment of sexually transmitted diseases

  • HIV counseling and testing

  • Harm reduction programs for injecting drug users

  • Prevention of mother-to-child transmission

  • Blood safety practices

  • Infection control in health care settings

  • Policy reforms to reduce the vulnerability of women and girls, and to ensure the legality and availability of proven HIV prevention strategies, such as use of condoms and clean syringes

  • Prevention programs specifically designed for people living with HIV

IMPACTS OF HIV/AIDS

The social, economic, and political impacts of HIV/AIDS affect all levels of society, from individuals and households to businesses and governments.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Socioeconomic Impacts on Households

By any measure, the death of a relative or other loved one to HIV/AIDS is a devastating event. In addition to the trauma of this loss, however, households may suffer a precipitous decline in living standards due to the loss of income previously generated by the victim and increased household spending on health-related goods and services. HIV/AIDS also lowers household income when family members reallocate time previously devoted to work to caring for a sick relative. Funeral expenses are another financial burden.

HIV/AIDS also has socioeconomic impacts on children. Rising poverty in general limits children’s access to education, which is intimately linked to the accumulation of human capital (Bell et al., 2004). As households lose income and reallocate resources, children are at greater risk of malnutrition. After a parent’s death, members of the extended family frequently care for the victim’s children. Results of surveys conducted in 10 countries of sub-Saharan Africa between 1992 and 2000 reveal that orphans tend to live in poorer households than nonorphans and to have lower school enrollment rates, even after controlling for household income (Case et al., 2004).

Socioeconomic Impacts on the Private and Public Sectors

Beyond households, the economic effects of HIV/AIDS multiply. As the disease takes a toll on workers in the private sector, rising production costs erode competitiveness and deter investments. Resulting declines in economic growth weaken the domestic tax base and decrease revenues. Within the public sector, as public servants fall ill and die, the efficiency of government agencies deteriorates. Further disruptions in public services occur when sick employees take extended leave or government agencies lag in hiring their replacements. The impacts of such disruptions are particularly severe for decentralized government services, such as local education and health care (Haacker, 2004).

The government sector most directly affected by HIV/AIDS is the health sector (Over, 2004). The demands on public health services rise sharply with the spread of the epidemic; at the same time, many health personnel are themselves infected (see Chapter 1). Prior to the availability of ART, the percentage of hospital beds occupied by HIV patients—ranging from 30 to 70 percent—indicated that HIV/AIDS was absorbing much of the existing capacity of health services in highly affected countries.

Military Conflict and HIV/AIDS

At present, Africa has more civil conflicts than any other region in the world. African peacekeeping troops have recently helped to stabilize Liberia,

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Burundi, and the Democratic Republic of the Congo. Thus it is important that the Joint United Nations Programme on HIV/AIDS (UNAIDS) conservatively estimates that men serving in armies have an HIV infection rate two to five times higher than that of their civilian counterparts (UNICEF, 2003). The South African government, for example, refuses to deploy its HIV-positive troops as peacekeepers (currently, 17 to 22 percent of South Africa’s defense force is HIV positive) (South Africa Department of Defense, 2002). The health and capacity of African soldiers and peacekeepers are of particular concern at a time when major powers are reluctant to engage further in peacekeeping operations in the region.

Armed forces also play a role in propagating the epidemic. Not only is rape a weapon of war, but some military personnel exploit vulnerable civilians (especially children and young people), promising money, food, or protection of shelter in exchange for sex. And when HIV-positive soldiers return home, they put their sexual partners at risk.

Finally, the breakdown of families and communities leaves children vulnerable to recruitment into armed groups. Two-thirds of the 300,000 children under age 18 involved in armed conflict worldwide are in Africa; many are under age 10 (Amnesty International, 2003). In addition to physical injury and disability, these children are at risk of sexually transmitted diseases, including HIV/AIDS (Uppard, 2003).

A CLOSER LOOK AT HIV/AIDS

HIV is a single-stranded ribonucleic acid (RNA) virus of the Retroviridae family. Following acquisition of HIV, individuals remain infected for life as a result of integration of the retroviral genome into the genome of various human cells. Without treatment, the virus causes a progressive weakening of the human immune system, eventually culminating in AIDS and death.

One of the major direct mechanisms by which HIV leads to illness is the selective infection and destruction of certain cells, known as CD4 lymphocytes or CD4 T-cells. This depletion in turn progressively disables an important component of the human immune system.

AIDS represents the most advanced stage of HIV infection, when severe complications occur; these include a variety of infections of the lungs, brain, eyes, and other organs, as well as debilitating weight loss, diarrhea, and certain cancers. The U.S. Centers for Disease Control and Prevention (CDC) has identified numerous opportunistic infections and cancers that, in the presence of HIV infection, constitute an AIDS diagnosis. In 1993, CDC expanded the criteria for an AIDS diagnosis in adults and adolescents to include a CD4 T-cell count at or below 200 cells per microliter in the presence of HIV infection (above the age of 5, persons with normally

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

functioning immune systems usually have CD4 T-cell counts in the range of 500 to 1,500 cells per microliter).

Transmission

The three primary routes of HIV transmission are sexual contact; perinatal transmission from infected mothers to their infants; and exposure to blood through injection drug use, transfusion, and accidental exposure to blood-contaminated sharps and needle sticks.

Heterosexual transmission is the major mode of spread of HIV infection in Africa (Cohn et al., 2001). High rates of heterosexual transmission in Africa may be partly attributable to a higher prevalence of genital ulcer disease, since genital ulcers increase the infectiousness of both male and female source partners (Piot and Laga, 1989; Plummer et al., 1991). Nonulcerative sexually transmitted diseases, such as gonorrhea and chlamydial infection, also increase sexual transmission of HIV (Laga et al., 1993; Plummer et al., 1991). Even more important, the infectiousness of a source partner increases with advancing immunodeficiency, that is, lower CD4 T-cell counts and higher viral loads (Quinn et al., 2000).

Vertical transmission of HIV from an infected woman to her infant can occur during intrauterine gestation, delivery, or the postpartum period via breastfeeding. The burden of pediatric HIV infection is directly linked to HIV prevalence among pregnant women, which exceeds 25 percent in some parts of Africa. The risk of mother-to-child transmission also correlates with increasing immunosuppression and maternal viral load.

Finally, people who receive blood or blood products from HIV-infected donors are at very high risk for HIV infection. Among injecting drug users, HIV is transmitted by parenteral exposure to HIV-infected blood via contaminated needles and other injection equipment. Accidental percutaneous, mucous membrane, and cutaneous exposures to blood-contaminated body fluids can occur in any health care setting, but are most common in resource-limited settings, where education and personal protective equipment may be lacking.

Preventing Transmission

More than two decades of research has firmly established that certain interventions can reduce high-risk sexual and needle-sharing behaviors that lead to HIV infection (Coates and Szekeres, 2004). In the United States, sex education is considered a cornerstone of the prevention of HIV, other sexually transmitted diseases, and teenage pregnancy (Kirby, 2001). An analysis of the “ABC” (abstinence, be faithful, use condoms) prevention model in Uganda indicated that delaying intercourse, reducing the number

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

of partners, and using condoms contributed to recently lowered HIV rates in that country (Stoneburner and Low-Beer, 2004). However, the ABC strategy fails to address some daunting problems. Chief among these is the fact that abstinence among young women in the face of sexual violence is difficult or impossible to ensure (Pettifor et al., 2004). A South African study found that women in violent relationships were 50 percent more likely to have HIV than their counterparts in nonviolent relationships (Dunkle et al., 2004). In addition, most young women in sub-Saharan Africa acquire HIV from steady partners or spouses (KIT et al., 1995).

As ART scale-up occurs in high-impact areas, voluntary testing and counseling will become increasingly prominent in comprehensive HIV/AIDS prevention strategies. The view that Africa should move swiftly toward widespread voluntary conseling and testing—especially for all patients admitted to hospitals or treated for TB—is gaining increasing support among medical experts and African leaders (DeCock et al., 2003; WHO, 2004). Brazil was the first country in the world to initiate universal voluntary counseling and testing, followed by Lesotho, whose HIV/AIDS prevalence rate of 30 percent is the fourth highest in the world. In Botswana (where HIV prevalence among adults stands at 38 percent), testing has been offered routinely in all public medical facilities, including antenatal clinics, since January 2004.

Natural History of Disease

The clinical spectrum of HIV infection ranges from asymptomatic carriage, to acute infection, to advanced immunodeficiency with opportunistic disease. Results of early retrospective studies of HIV-infected homosexual men in San Francisco suggested that the incubation period from acute HIV infection to development of AIDS is 9.8 years (Bacchetti and Moss, 1989). Other early studies led to estimates of the incubation period ranging from 6.5 to 13 years, with an average of 8–9 years.

As HIV-related immunosuppression progresses, the spectrum of illness seen among the infected in the developing world differs from that seen in HIV-infected residents of western countries. In Africa, for instance, people with early HIV infection are more likely to develop TB, bacterial pneumonia, or septicemia. AIDS itself is more often associated with “slim disease” or disseminated fungal infections than with the classic opportunistic infections of western countries.

Because of their immunologic immaturity, the progression of HIV/ AIDS in infants and young children is accelerated following vertical transmission from HIV-infected mothers. Without treatment, most HIV-infected children in Africa die before their third birthday (Chakraborty, 2005).

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Comorbidities and Cofactors in Disease Progression

Many individuals who are either at risk for or become infected with HIV are also malnourished and coinfected with other diseases (see the discussion above); some also suffer from substance abuse and mental illness. A full understanding of the negative synergy between these comorbidities and HIV is just beginning to emerge; however, many researchers have shown that opportunistic infections—especially TB—increase the risk of death (Seage et al., 2002; Whalen et al., 2000). Recent evidence has also shown that malaria temporarily increases HIV viral loads (Kublin et al., 2005), theoretically increasing HIV transmission 50 percent during periods of active illness (Whitworth and Hewitt, 2005). HIV also worsens malaria in pregnant women, who experience more complications, as well as an increased risk of adverse birth outcomes, when they are HIV coinfected (ter Kuile et al., 2004).

Both acute and chronic malnutrition also reduce immunity to and accelerate the progression of HIV/AIDS (Anabwani and Navario, 2005). At the macro level, bidirectional links exist between HIV/AIDS and food security within households and entire regions affected by acute famine (Griekspoor et al., 2004). Decreased availability of food also affects HIV/ AIDS transmission by forcing people to adopt risky survival strategies, such as transactional sex.

TREATMENT AND CARE

Antiretroviral Therapy2

The goal of ART is to inhibit viral replication while minimizing the side effects and toxicities of currently used drugs. The inhibition of HIV replication permits restoration of the immune system. Although viral eradication from the host genome is not yet possible, appropriate lifelong administration of antiretrovirals (plus other drugs to prevent opportunistic infections), can reduce AIDS-related mortality to almost zero for the remainder of a patient’s life, allowing the patient to enjoy an enhanced quality of life and remain productive.

The benefits of antiretrovirals may be clinically observed in many ways, but restoration of immune function and suppression of viral replication are best evaluated by laboratory testing. The goal of therapy is to achieve a CD4 cell count greater than 200 mm3 and an “undetectable” viral load

2  

This section is largely drawn from IOM (2005).

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

(< 50 copies/ml). With an effective regimen, these goals should be achieved within 4–6 months of initiating ART and can be maintained indefinitely if the patient continues to take the drugs.

There are now more than 20 drugs used to treat HIV/AIDS, falling into four classes. The first three classes of drug, affecting viral enzymes, are the nucleoside analogue reverse transcriptase inhibitors (NRTIs, exemplified by the very first antiretroviral, zidovudine or AZT, introduced in 1987); the nonnucleoside reverse transcriptase inhibitors (NNRTIs); and protease inhibitors (PIs). The most recently developed class of drugs, fusion inhibitors, block the entry of HIV into host target cells such as CD4 lymphocytes. In addition to possessing separate mechanisms of action, each class also possesses unique effects and toxicities.3

Triple combinations are the most effective way to treat HIV infection. Highly active antiretroviral therapy (HAART) refers to a daily regimen of treatment involving three or more drugs from at least two of the above classes. Mono or dual therapy, used at the start of the epidemic, is less effective and is associated with regimen failure and drug resistance.

Specific guidelines for use of antiretrovirals change regularly as new drugs are approved and the drawbacks of older drugs become more apparent. A comprehensive reference on the use of antiretroviral agents in HIV-infected adults and adolescents was recently released by the U.S. Department Health and Human Services (DHHS, 2005), and regular updates are provided at the reference website. It should be noted, however, that these guidelines derive from clinical and translational research undertaken in the United States and Europe, and that questions regarding their applicability to resource-limited settings remain.4 Although guidelines based on Western experience provide a good starting point for scaling up ART in resource-limited settings, ongoing research conducted in these settings will be critical to the guidelines’ ultimate success.

3  

For example, different drugs within the NRTI class may produce lactic acidosis, fatty liver, peripheral nerve damage, inflammation of the pancreas, and anemia. Drugs within the NNRTI class often cause rash and liver function abnormalities. Drugs within the PI class may produce kidney stones and gastrointestinal side effects such as nausea and diarrhea. Combining antiretrovirals and TB treatment can also pose difficulties and require special monitoring.

4  

For example, in settings where patients’ genetics and metabolic pathways differ from those of clinical trial populations, unexpected drug toxicities could develop. Moreover, different strains (clades) of virus circulate in Africa and Asia, raising questions about unexpected drug resistance patterns and the general applicability of drug sequencing algorithms developed in western countries. Finally, different opportunistic pathogens could change the clinical manifestations of HIV/AIDS in resource-limited settings and create new drug–drug interactions between antiretrovirals and specific treatments for opportunistic infections.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

The Problem of Antiretroviral Resistance

Because HIV undergoes high rates of replication and turnover, its potential for developing drug resistance is great. It is currently believed that in the United States, 50 percent of patients receiving ART harbor a virus that is resistant to at least one antiretroviral drug (Richman et al., 2004). Resistance to a single drug or an entire class can develop during drug therapy (Clavel and Hance, 2004), or drug-resistant viral strains may be transmitted de novo to new hosts. One of the greatest concerns in scaling up ART in developing countries is the potential for drug resistance to develop and spread on a large scale, a situation that would ultimately jeopardize the treatment of all untreated populations exposed to high burdens of drug-resistant virus. The World Health Organization recommends that countries planning to implement ART programs concurrently introduce sentinel surveillance systems for HIV drug resistance.

The presence of a resistant virus in a population also complicates the delivery of ART at the local level because it necessitates diagnostic tests for resistance testing, the expertise to interpret and act upon the test results, and a larger armamentarium of antiretroviral drugs. These factors, in turn, increase the complexity and cost of treatment and make it difficult for midlevel practitioners to treat large populations.

While many factors can promote resistance to antiretroviral drugs in an individual patient,5 the single most important safeguard against the development of drug resistance is adherence to the prescribed regimen. If at least 95 percent of doses are taken, there is a greater than 80 percent chance that the viral load will drop to less than 500 copies/ml; if fewer than 95 percent of doses are taken, fewer than 50 percent of patients achieve this level of viral suppression (Bartlett, 2004). Any regimen that does not completely suppress viral replication will eventually lead to drug resistance.

Treatment and Prevention of Opportunistic Infections

When the immune system of an HIV-infected individual is depleted to the point of AIDS, patients develop a range of secondary opportunistic infections such as TB; Pneumocystis pneumonia; cryptococcal meningitis; Toxoplasma brain abscesses; and HIV-related cancers, including Kaposi’s sarcoma and lymphoma.

5  

Examples of such factors include the improper prescription of antiretrovirals; underdosing, leading to suboptimal drug levels; poor adherence to medication; missed doses of one or more drugs due to local stock-outs; altered drug metabolism; and the presence of tissue “sanctuaries” where virions evade the action of specific drugs.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Although potent combination antiretroviral treatments have reduced the incidence of opportunistic infections for many HIV-infected patients in developed countries, such infections remain a prominent feature of later stages of HIV infection and the common AIDS-defining events. A recent report published by CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America lists treatment recommendations for 28 opportunistic infections due to protozoa, bacteria, fungi, and (nonretroviral) viruses in HIV-infected adults and adolescents (Benson et al., 2004).

Strategies for prevention of opportunistic infections in developing countries have not yet been fully developed. When available and tolerated, however trimethoprim-sulfamethoxazole (a broad-spectrum antibiotic) given to patients with CD4 cell counts below 200 mm3 is generally accepted as a highly beneficial complement to ART (personal communication, Robert Schooley, University of California-San Francisco, February 14, 2005).

Comprehensive Health Care for HIV/AIDS in Developing Countries

Ideally, a comprehensive approach to treatment and care for people with HIV/AIDS includes a range of components, including the following:

  • Community and national treatment, care, and prevention guidelines

  • Education and awareness programs

  • Programs to address stigma and discrimination

  • Voluntary counseling and testing with informed consent in health facilities, along with services targeting vulnerable and difficult-to-reach populations

  • Prevention of mother-to-child transmission

  • Prevention and treatment of opportunistic and sexually transmitted infections

  • Antiretroviral therapy and monitoring, including essential laboratory and clinical backup and drug management systems

  • Embedded operations research programs designed to elucidate the most effective approaches to HIV/AIDS care and delivery in resource-limited settings

  • Adherence support

  • Social protection, nutrition, and welfare and psychosocial services

  • Palliative and home-based care

  • Bereavement support

In reality, however, different models of comprehensive health care delivery for HIV/AIDS will be needed to respond to the diverse requirements

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

and capacities of the developing countries in which the infection is endemic. The introduction of treatment and care should also be appropriately phased. For example, ART should be initiated only if certain minimum conditions are met, including community preparedness, counseling and testing with informed consent, training of personnel for provision of ART and follow-up, and uninterrupted supplies of antiretroviral drugs. One key element is the training, support, accreditation, and quality control of providers, including those in both the public and private sectors (WHO, 2003a).

Another priority is reliable and confidential systems for medical record keeping (in some cases, such systems will be introduced into health facilities with no previous experience with using written medical records). Some countries are planning to use traditional paper-based systems combined with patient identity or photo cards. Others are exploring the potential use of new technologies, such as “smart cards” or fingerprint readers, bar-coded drug packaging, and electronic databases for patient and drug monitoring. In Brazil, for example, most patients now receive a magnetic card, which they present to receive treatment (Attawell and Mundy, 2003).

Finally, caregiving and palliative measures—generally defined as pain and symptom management, advance care planning, prioritization of life goals, and support for individuals and families throughout the course of disease—will be essential elements of any comprehensive treatment program. This is a pressing need in Asia (Coughlan, 2003) as well as in Africa, a continent currently experiencing, in the words of one local hospice educator, “an epidemic of death” (Ramsay, 2003:1813). One survey of 48 African palliative care services for patients with AIDS found that 94 percent had experienced obstacles, especially a lack of trained providers; stigma; and government restrictions limiting access to narcotics such as oral morphine, which controls pain and diarrhea in the terminal phases of AIDS and allows many patients to stay in their homes without the cost or disruption of transfer to a hospital (Harding et al., 2003). Research from Uganda also suggests that dying patients’ greatest need is relief of pain and other terminal symptoms (Kikule, 2003).

Uganda is the first and only African country thus far to make palliative care for people in the terminal stages of AIDS and cancer part of its national health plan (Ramsay, 2003). Although only a small number of eligible Ugandans are currently accessing palliative care and free oral morphine, the government is revising its laws to enable wider prescribing by community nurse specialists. The need for better community-based palliative and end-of-life models in many low-resource settings heavily impacted by HIV/AIDS is reflected in the fact that 15 percent of PEPFAR funds in target countries is allocated to palliative care initiatives.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Entry Points for HIV/AIDS Treatment and Care in Developing Countries

Experience with pilot programs has revealed several ways to integrate prevention and care efforts through various clinical entry points, including voluntary counseling and testing, sexual and reproductive health services, and other health services.

Voluntary Counseling and Testing

Voluntary counseling and testing with informed consent is the key point at which people learn their HIV status and are offered care services, as well as behavioral and preventive advice. Studies have shown that voluntary counseling and testing consistently increases safe-sex behaviors among people who are HIV positive (CDC, 2000; Weinhardt et al., 1999), as well as those who are HIV negative (Spielberg et al., 2003; The Voluntary HIV-1 Counseling and Testing Efficacy Study Group, 2000).

Until recently, however, access to voluntary counseling and testing in countries most severely affected by HIV/AIDS has been limited. As a result, there are few developing countries in which more than 10 percent of the adult population has been tested (Fylkesnes and Siziya, 2004). Greater provision of HIV treatment should create greater demand for counseling and testing services (MSF South Africa et al., 2003; Mukherjee et al., 2003). The increasing need for such services in developing countries—reaching geographically remote areas as well as community clinics and networks—must parallel the scale-up of other HIV-related services. Otherwise, limited availability of testing and counseling could become a bottleneck to expanded treatment and care. The actual training of providers in voluntary counseling and testing takes 1 to 8 weeks (Heiby, 2004).

Rapid testing methods that can provide reliable results within minutes and require relatively little laboratory capacity are a practical tool for voluntary counseling and testing outreach settings in developing countries. More than 60 rapid tests have been developed and used overseas (Cohen et al., 2003). For confirmation of HIV status, a two-step rapid testing strategy may be more cost-effective than the standard combination of enzyme immunoassay followed by a confirmatory Western blot used in most Western countries (Ekwueme et al., 2003).

UNAIDS has identified several critical elements of counseling and testing programs: testing should be voluntary, results should be confidential, testing should focus on an individual client’s needs, HIV-positive and HIV-negative persons should be referred for ongoing support, and stigma-reducing activities should be incorporated into the services provided (CDC, 2004; UNAIDS, 2000). Unfortunately, anticipated and actual stigma directed at HIV-infected individuals still constrains the use of testing services

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

(Parker and Aggleton, 2003). HIV-infected women who disclose their status are also vulnerable to partner violence and economic instability (Mamam et al., 2000, 2002).

Sexual and Reproductive Health Services

Sexual and reproductive health services, including clinics for treatment of other sexually transmitted infections, are another entry point for HIV/ AIDS prevention and care. Antenatal services provide access to programs to prevent mother-to-child transmission of HIV and allow HIV-infected women to receive treatment and care during and after pregnancy, as well as advice for future pregnancies (WHO, 2003b). Outreach services for targeted populations, including sex workers, men who have sex with men, and injecting drug users are further channels for information.

Routine testing of pregnant women (with the right to refuse) is recommended as part of worldwide efforts to expand access to ART and programs to prevent mother-to-child transmission of HIV, in the 2004 joint United Nations and World Health Organization policy statement on HIV testing (UNAIDS Global Reference Group on HIV/AIDS and Human Rights, 2004). Without intervention, 35 to 40 percent of HIV-positive women transmit HIV to their infants. With drug prophylaxis and formula feeding, transmission is reduced to 5 to 10 percent, and with combination ART, transmission falls below 1 percent (Nolan et al., 2002). The consensus of the international public health community is to recommend the unrestricted use of any of the short-course antiretroviral regimens of validated efficacy for prevention of mother-to-child transmission, especially in areas of high HIV prevalence (UNAIDS, 1999).

Other Health Services

Other health services, in particular TB programs, have the potential to recruit large numbers of people into HIV treatment. As the TB and HIV/ AIDS epidemics continue to fuel each other, increased collaboration between programs is essential. It has also been proposed that TB programs assist in the delivery of ART and HIV prevention services. For example, the Haiti Partners in Health Program has found that the directly observed therapy short course (DOTS) approach used for TB treatment can be equally effective for ART (Farmer et al., 2001). Others argue, however, that DOTS and ART strategies are not readily interchangeable, since TB treatment is time limited, while ART is lifelong. Concerns also exist regarding the risk of cross-infection in TB treatment facilities if HIV-infected individuals come into frequent contact with contagious TB patients.

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

The World Health Organization’s Strategy for Chronic Disease Care in Developing Countries

Although HIV infection has dramatically lowered life expectancy in much of sub-Saharan Africa, life expectancy in many developing countries has continued to increase over the past decade. Chronic conditions such as diabetes and cardiovascular disease now account for roughly half of all health services required in the developing world (WHO, 2002a). To address these new trends in human health, the World Health Organization recently proposed a global strategy for designing and reconfiguring health care systems to better meet the needs of people with chronic diseases (see Box 2-1). This strategy could serve as a model for delivering comprehensive services to HIV-infected people. The approach starts with education and voluntary counseling and testing, followed by the initiation of ART and prevention of opportunistic infections, and culminating in the medical management of advanced HIV/AIDS by progressively tiered health professionals.

BOX 2-1
The World Health Organization’s Strategy for Comprehensive Chronic Disease Care in the Developing World

  • Shift the emphasis from acute, episodic care to providing continuity of care with planned visits and regular follow-up.

  • Develop health policies, collaboration, legislation, and health care financing to support comprehensive care strategies.

  • Emphasize delivery of services at the primary care level to ensure the broadest access to effective care.

  • Develop effective communication and referral systems among the primary, secondary, and tertiary levels of health care.

  • Center care on the patient, educate patients about their disease so they can become active participants in their care, and promote adherence to long-term treatment regimens.

  • Link care to community resources; provide education and support to family and community members to assist in care.

  • Emphasize prevention.

  • Monitor and evaluate the quality of services and long term patient outcomes.

SOURCE: Kitahata et al. (2002).

Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×

Issues in Providing Antiretroviral Therapy and HIV/AIDS Care in Resource-Limited Settings

Many lessons are being learned in the early stages of providing ART in resource-limited settings. Among these is identification of the following needs: to strengthen health care systems; to define adequate infrastructure encompassing clinical care, laboratory, and pharmacy facilities for the delivery of ART; to overcome chronic shortages of staff at all levels of clinical care facilities; and to rethink training strategies and methods while incorporating continuing education, given the rapidly evolving nature of ART (Attawell and Mundy, 2003).

Although a detailed discussion of challenges and solutions is beyond the scope of this report, innovative programs will continue to serve as international demonstrations of treatment and care approaches. At the same time, many medically eligible patients will not have access to ART over the next few years because of financial or other constraints. Socioeconomic, geographic (rural versus urban), and gender criteria for determining which patients will receive free or subsidized ART need to be carefully defined to ensure equitable access. It has been argued that governments that make deliberate choices about rationing ART and then explain and defend those choices are more likely to sustain economic development and social cohesion over the course of the epidemic than those that avoid the public policy debate and otherwise skirt decision making about equitable access to ART and other forms of HIV/AIDS care (Rosen et al., 2005).

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Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
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Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
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Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
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Page 53
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 54
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 55
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 56
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 57
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 58
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 59
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 60
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 61
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 62
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 63
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 64
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
Page 65
Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
×
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Suggested Citation:"2 Confronting HIV/AIDS on the Ground." Institute of Medicine. 2005. Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS. Washington, DC: The National Academies Press. doi: 10.17226/11270.
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Healers Abroad:Americans Responding to the Human Resource Crisis in HIV/AIDS calls for the federal government to create and fund the United States Global Health Service (GHS) to mobilize the nation�s best health care professionals and other highly skilled experts to help combat HIV/AIDS in hard-hit African, Caribbean, and Southeast Asian countries. The dearth of qualified health care workers in many lowincome nations is often the biggest roadblock to mounting effective responses to public health needs. The proposal�s goal is to build the capacity of targeted countries to fight the HIV/AIDS pandemic over the long run. The GHS would be comprised of six multifaceted components. Full-time, salaried professionals would make up the organization�s pivotal �service corps,� working side-by-side with other colleagues already on the ground to provide medical care and drug therapy to affected populations while offering local counterparts training and assistance in clinical, technical, and managerial areas.

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