AIDS and Behavior An Integrated Approach (1994) / Chapter Skim
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4 DISEASE PROGRESSION AND INTERVENTION
4 DISEASE PROGRESSION AND INTERVENTION
Pages 124-154
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From page 124... ...
Chief interactions reviewed here include: t1J HIV infection of the brain and the effects HIV has on the central nervous system; {2J effects of interactions among HIV infection, substance use, and mental illness and the unique medical care and treatment issues associated with such interactions; en cl {3J the relationship between psychosocial factors and HIV infection for inclivicluals with the disease, as well as for their loved ones and caregivers.
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From page 125... ...
Many can be considered secor~dary complications of HIV infection, resulting from opportunistic infections or systemic organ dysfunction that follows from immune deficiency induced by HIV infection. Among the major CNS complications of AIDS are cerebral toxoplasmosis, primary CNS lymphoma {an opportunistic neoplasm associated with Blymphocyte infection by Epstein-Barr virus)
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From page 126... ...
However, after further clarification of the features of the syndrome, with its pathology and the clinicalpathological correlations, CMV infection no longer seemed to provide an adequate explanation tNavia, Cho, Petito, et al., 1986J. Because this syndrome was unlike any known complications of immunosuppression previously described in other populations, such as cancer and transplant patients, speculation turned to the same putative agent that caused AIDS itself; and when HIV was then identified {as LAV and HTLV-IIIJ research began to test whether this virus might not only cause immunosuppression, but might more directly cause the AIDS dementia complex {Price et al., 1988J.
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From page 127... ...
STAGING AND CELLULAR SITES OF CENTRAL NERVOUS SYSTEM INFECTION IN AIDS DEMENTIA CoMP~EX The core features of the AIDS dementia complex have now been well characterized, and a descriptive staging system, useful to provide a common vocabulary for both clinical practice and clinical investigation, has been developed {see Price, 1994; Sidtis, 1994J. Nonetheless, more precise defining characteristics still must be developed in order to standardize clinical trials.
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From page 128... ...
AIDS dementia complex shares with these disorders a slowing of thinking and concentration along with motor dysfunction, in contrast to the cortical dementias such as Alzheimer's disease and Creutzfel~tJacob disease, in which amnesia, aphasia, apraxia, and the like are more characteristic. Understanding the nature and physiology of brain dysfunction in AIDS patients has both practical and theoretical importance.
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From page 129... ...
The reason for this seemingly paradoxical finding remains to be explained {paradoxical because reduced metabolism might have been anticipated on the basis of symptoms, and because these structures appear to be more susceptible to HIV infection than cortexJ. MECHANISMS OF CENTRAL NERVOUS SYSTEM INJURY A complex picture emerges from pathological studies indicating that productive HIV infection in the brain occurs in cells of bone marrow origin {monocyte-macrophages and microgliaJ rather than in the neuroectoclermal cells {nerve cells and other supporting cells in the brain such as oligodendrocytes and astrocytesJ that perform the specialized work of the CNS.
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From page 130... ...
Recent experiments have raised other possibilities to account for HIV-elicited neurotoxicity. Astrocytes, another critical class of supporting cells in the nervous system, produce growth and survival factors that are essential for normal brain function isee Lu et al., l991J.
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From page 131... ...
Some putative cell-coded neurotoxins are quinolinic acid (an endogenous excitatory amino acidJ, nitric oxide, Tumor Necrosis Factor, NMDA agonists, and arachidonic acid metabolites {Benos et al., 1994, Brenneman et al., 1988; Dawson et al., 1993; Epstein and Gendelman, 1993; Carry and Koch, 1992; Guilian, Vaca, and Noonan, 1990; Heyes et al., 1991; Heyes, Saito, Crowley, et al., 1992; Kaiser, Offerman, and Lipton, 1990; Lipton, 1991, 1992, 1994; Masliah et al., 1994; Pulliam et al., 1991; Toggas et al., 1994; Wah} et al., 1989; Werner et al., 1991; Wesselingh et al., 1993~. A picture is emerging of multiple toxins acting in concert as part of dysregulatec3 cytokine cascades triggered by immune responses or by viral signals, together disrupting or destroying neuronal function in selected brain regions.
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From page 132... ...
Based on the foregoing, the next step is to see if new agents to prevent the neurologic sequelae of AIDS can be designed and tested in culture models, experimental animals, and the clinic, and to determine if there are any animal models of predictive value, other than nonhuman primates. These questions may seem daunting, but studies on the AIDS dementia complex have evolved in a short period of time from a primitive state of empirical observations to experiments with possible direct therapeutic implications, not only for ADC, but also for other neurological and psychiatric diseases, especially those mediated by viruses or immune dysfunction.
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From page 133... ...
The pathogenesis of ADC involves processes that have been observed in animal models {usually of viral diseases studied as models of degenerative disordersJ, but that have received less attention in human diseases with a known viral cause. Unlike most other human infections, HIV infection is characterized by long latency, a seeming lack of direct nerve cell destruction in the absence of immunosuppression {which HIV first induces before then affecting the brainy, and the principally indirect mechanisms of brain injury alluded to earlier.
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From page 134... ...
CHNICAL SIGNIFICANCE OF AIDS DEMENTIA COMPLEX The primary motivation to study ADC and HIV infection of the CNS is to treat the disability they cause. While the prevalence of ADC is still somewhat uncertain, it remains a significant complication of HIV infection, and its severe impact on the lives of patients makes it an important target of prevention and treatment.
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From page 135... ...
DRUG USE AND HIV/AIDS The large number of drug injectors already infected with HIV pose a significant challenge to the medical care system to recognize and treat the varied clinical manifestations of HIV infection and disease in this high-risk population. Treatment of (lrug users who are at risk for or already infected with HIV is complicated by
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From page 136... ...
Natural History of HIV Infection Among Drug Users Most studies that have described rates of progression to AIDS or clinical manifestations of HIV disease in drug users have been performed among cohorts in which the date of primary HIV infection is unknown (Des JarIais et al., 1987; Selwyn, Alcabes, Hartel, et al., 1992J. These cohorts have tended to include many with advanced HIV infection at the time of study.
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From page 137... ...
Given the relationship between HIV infection and co-infection with other organisms, the evidence of high levels of both hepatitis B and hepatitis C infection among drug users, and the key importance of liver disease in this population, it also will be important to clarify further the clinical expression and outcome of hepatitis C infection in co-infected groups {Donahue et al., 1991; Esteban et al., l9X9; Haverkos end Lange, 1990; Kreek, 1983; Novick et al., 1988; Stimmel, Vernace, and Schaffner, 1975; van den Hoek et al., l990J. Moreover, the prognostic importance of standard laboratory markers used in the assessment of HIV disease state among drug users {e.g., CD4+ T-lymphocyte subsets, Beta-2-microgiobulin, neopterin, and hematologic indicesJ will be important to reassess, given evidence that some markers may not be as useful in drug users as in other populations.
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From page 138... ...
require long-term medical regimens, often involving multiple medications, the levels of adherence among drug users in a variety of treatment settings must be examined. In particular, the relationship between active substance abuse and adherence to medical care is a critical question requiring further study.
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From page 139... ...
Drug injectors as a group are likely to have a high lifetime prevalence of depression, anxiety, personality disorcler, and other psychiatric diagnoses {Batki, 1990a; Rounsaville et al., 1991~. In addition, underlying psychopathology, especially depression, was identified as a predictive factor for persistent risk-taking behavior among drug users in one study that linked continued needle sharing to depression, and certain psychiatric disorders may be associated with lack of engagement with or follow-up with medical care for HIV infection among drug users {Batki, 1990a)
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From page 140... ...
These questions also hold relevance for basic policy issues concerning the integration of substance abuse treatment into mainstream medical education and practice (Lewis et al., 1987J, a trend that has been stimulated in part by the AIDS epidemic {National Commission on AIDS, l991bJ. INTERVENTIONS FOR THE SERIOUSLY MENTALLY Ice The convergence of psychiatric disorders, substance abuse, and HIV among those who are also severely mentally ill raises difficult questions about appropriate treatment, similar to issues related to treatment of injection drug users.
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From page 141... ...
The management of HIV infection carries both diagnostic and therapeutic implications that may not be directly related to HIV infection per se. It may be difficult to distinguish depression or anxiety from the AIDS dementia complex, because many symptoms overlap.
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From page 142... ...
It is probable that CNS modulation of immune defenses is relatively minor in relation to the overwhelming influence of the virus and other determinants on the type and potency of immune responses to HIV. The bidirectional relationship between the CNS and the immune system, including nerve cell attachments to immune organs and how those may modify immune events, is nonetheless likely to influence the dynamics of HIV infection, although measuring such effects in HIV-infected persons may be extremely difficult because of the influence of cofactors, such as substance abuse, among some such individuals.
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From page 143... ...
But it is not yet known whether HIVrelated situations inherently are more stressful than others, or if avoidant coping itself is inherently maladaptive {Folkman, 1993J. Cognitive coping strategies, however, such as positive reinterpretation, gaining a sense of control over events, and effecting positive changes in daily life, seem to promote psychological wellbeing throughout the course of the disease {Hart et al., 1990; Ratkin et al., 199 1; Storosum, Van Den Boom, and Beauzekom, 1 990J.
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From page 144... ...
These mixe~l findings suggest that people adjust to living with AIDS by adopting cognitive coping strategies. Some consciously adopt strategies for minimizing stress, anxiety, and depression, while others achieve it through the actions involved in living with AIDS, such as investigating new drug therapies, educating oneself about the illness, taking control of one's legal and financial affairs, and planning the end of one's life {Folkman et al.
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From page 145... ...
Much remains to be learned about how people from various gender, racial/ethnic, and cultural groups, and with different risk factors, such as injection drug users, cope with their own and others' HIV status, including not only general psychological strategies, but also motivation or resistance to adherence to medical treatment and its implications for disease progression. Future interventions should be brief, be theorybased, be effective in teaching coping skills, include techniques for maintaining such skills, and produce manuals that enable replication of the interventions elsewhere {Folkman, 1993J.
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From page 146... ...
In major cities, for example, 26 percent of AIDS caregivers are heterosexual men, 42 percent are heterosexual women, 25 percent are gay or bisexual men, and 7 percent are lesbian or bisexual women {Turner, Catania, and Gagnon, 1994~. The caregiving role is thus highly non-normative for a large proportion of AIDS caregivers.
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From page 147... ...
This likely reflects the fact that gay men constituted over 60 percent of AIDS cases reported between 1981 and 1993 {CDC, 1994J and that one-third to one-half of gay men with AIDS are cared for by gay peers {McCann and Wadsworth, 1992; Turner, Catania, and Gagnon, 1994J. However, other populations of caregivers E.g., those who care for HIV-infected drug usersJ also deserve attention.
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From page 148... ...
Formal Caregivers: Health Care Professionals As with informal caregivers, not much is yet known about formal caregivers. For the most part, research has focused on how health care workers deal with the stress and burnout of providing care to AIDS patients.
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From page 149... ...
The psychological and physical implications of AIDS caregiving for health professionals undoubtedly is affected by their attitude toward AIDS. Surveys among nurses, physicians, dentists, social workers, psychiatrists, and health profession students are notable for revealing a consistent aversion among caregivers to the HIV/ AIDS disease, to patients and their lifestyles, and to caregiving work itself {Silverman, 1993J.
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From page 150... ...
by gender, race/ethnicity, and the attitudes family members have toward homosexuality iTakigiku, Brubaker, and Hennon, 1993~. Similar considerations should be applied to studies of caregiving among injection drug users and others.
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From page 151... ...
RECOMMENDATIONS FOR DISEASE PROGRESSION AND INTERVENTION 4.1 The committee recommends that NIMH continue research on the pathogenesis of HIV infection of the brain, including the factors controlling virus replication such as local immune defenses and changes in the viral genome determining neuropathogenicity. 4.2 The committee recommends that NIMH continue research on the pathobiology of nervous system injury underlying the AIDS dementia complex, including the morphological, biochemical, and molecular basis of neuronal dysfunction related to viral anal cellular gene expression.
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From page 152... ...
4.10 The committee recommends that all relevant NIH institutes eliminate systemic barriers to the inclusion of injection drug users and other substance abusers in AIDS and AIDS-related clinical trials. 4.11 The committee recommends that NIAAA, NIDA, and NIMH support research on the utilization of health resources by people with AIDS, including substance abuse and mental health treatment programs.
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From page 153... ...
4.15 The committee recommends that NIAAA, NIDA, and NIMH support research on how families {broadly defined to include persons who consider themselves to be family through mutual commitment) from diverse racial/ethnic, socioeconomic, and sexual orientation backgrounds cope with the reality of having family members who are infected with HIV or have AIDS.
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