Older adults account for 10% to 18% of those estimated to be infected with HIV. More than half of this older HIV-positive group are of African-American and Hispanic origin, indicating greater risk for ethnic and racial minority older adults. Currently, approximately 17% of people in the United States living with AIDS are 50 years old or older, but there are geographic variations.¹ In addition to primary infection in later life, with the wide use of highly active antiretroviral therapy (HAART), adults who were infected in earlier life are living longer. As a result, the proportion of older people living with HIV disease quintupled between 1988 and 2000.

HIV has traditionally been thought of as a disease of young persons. However, the primary routes of transmission, sexual activity and drug use, usually associated with young adulthood and middle age, are also the most common routes for infection for older adults. Many health care providers do not know this and thus do not discuss issues of sexuality or substance use with seniors. Older adults themselves are often unaware of the risk factors for HIV infections or do not see themselves as being at risk for infection. Compounding this issue is that older adults are not typically targeted for prevention or safe-sex education.

For older men in the United States, the most frequent exposure category is men having sex with men, but heterosexual and intravenous drug use exposures are increasing. Certain factors increase the risk for older men. First, unlike younger men, older men are less likely to reveal their sexual orientation to health care workers, limiting the opportunities for prevention education. Second, drugs such as sildenafil (Viagra) have contributed to increased rates of heterosexual, homosexual, and bisexual activity, but many seniors do not use condoms consistently. Third, reports from Florida reveal an added risk for older men. Prostitutes who are HIV-positive have used older men’s insulin needles to inject drugs and then returned the syringes to their packaging to avoid detection. The unsuspecting older men then used the dirty needles.

Older women are more commonly exposed through heterosexual transmission, but intravenous drug use is also a route of exposure. Older women are more vulnerable to HIV infection than their younger counterparts because of age-related changes in vaginal mucosa after menopause. The vaginal wall is thinner and lubrication is reduced, leading to a greater likelihood of vaginal trauma during intercourse. Older women associate condom use with prevention of pregnancy and, because this is no longer a concern after menopause, are less likely than younger women to use condoms. A recent source of intravenous drug use exposure among older adults with diabetes is the sharing of insulin needles, syringes, and glucose monitoring needles to save money.

There are unique characteristics that distinguish the presenting symptoms, diagnosis, and course of HIV disease in older adults. Seniors are less likely to be tested for HIV than younger persons, because HIV infection symptoms are attributed to other diseases common among the elderly. Thus HIV infection often is first diagnosed at later stages of infection. Older HIV- positive adults are more likely than younger adults to have comorbid medical conditions commonly seen in the aging population and to require concomitant medications, complicating symptom assessment and treatment choices. Age-related declines in immune function leave older adults more vulnerable to opportunistic infections, with increased rates of HIV-related complications, more rapid progression to AIDS, and lower survival rates than in younger adults with HIV disease.²

Although HIV treatment guidelines have been developed for other patient populations, no specific treatment recommendations exist for older adults. Nevertheless, administration of HAART to HIV-positive older adults is effective and produces greater reductions in mortality rates compared to those in younger HIV-positive adults. Little is known about age-specific HAART drug actions, drug–drug interactions, drug–disease interactions, or adverse events. For example, recent studies have found that older adults are more likely to experience toxicities from HAART, including dyslipidemia, insulin resistance, and pancreatitis. A person’s age does not interfere with HAART’s ability to reduce viral load, but CD4 recovery was lower in older people compared to younger ones, likely due to age-related decreased activity of the thymus gland, where CD4 cells are made.

With aging, the total numbers of immune cells and concentration of immunoglobulins do not change, but a redistribution does occur.⁴ Increases in immunoglobulin (Ig)A and IgG and decreases in IgM are seen. The main age-related cellular changes, however, occur in the ratios of subpopulations of T lymphocytes. There are increases in immature cell forms and reductions in cytotoxic and natural killer cells. The delayed-sensitivity reaction is less vigorous, and immunity to virus infections is reduced. T cells have been shown to have fewer surface receptors and B cells fewer immunoglobulin markers. As a result of these changes, at time of HIV diagnosis, older adults have lower CD4 counts than younger patients.

Hepatic metabolic functioning declines with age, in part reflecting reduced hepatic perfusion and reductions in liver size. The oxidative pathways, especially cytochrome isoenzymes 2D6 and 1A2, are those most affected, particularly in men, with relative sparing of conjugation. These functional changes result in increases in the bioavailability of drugs (through half-life prolongation) and metabolites that are normally inactivated through phase I of hepatic enzyme biotransformation. Ritonavir itself can inhibit the activity of cytochrome P 2D6, so that in an older adult, use of this antiretroviral can increase both beneficial and adverse effects of many psychotropic medications.

Renal function normally declines with aging as a result of a decrease in glomerular filtration rate and renal blood flow, leading to reductions in creatinine clearance. This has important implications for drugs excreted through the kidneys, such as lithium and buspirone. Older adults are more susceptible to develop the syndrome of inappropriate antidiuretic hormone secretion (SIADH) from medications, such as the selective serotonin reuptake inhibitors (SSRIs) and carbamazepine.

Plasma concentrations are reduced with aging and malnutrition, and hepatic disease causes further declines. The consequence of this reduction is that free plasma concentrations of protein- bound medications (i.e., the pharmacologically active component) remain the same, but the bound portion is reduced. Thus the therapeutic and toxic effects occur at lower total drug plasma concentrations. This is particularly relevant for anticonvulsants used to treat mood disorders.

The prevalence of schizophrenia in older HIV-positive adults (3%) is higher than in the general population, but similar to the prevalence in younger HIV-positive adults. Mortality in persons
with schizophrenia is 2 to 4 times greater than in the general population, and nonadherence to nonpsychiatric medications is a major contributing factor.⁷,⁸ Successful treatment of HIV infection requires consistent adherence to 90% of prescribed antiretrovirals; thus patients with schizophrenia have poorer treatment success. This partly explains the high prevalence of schizophrenia (12.8%) among HIV-positive nursing home residents with dementia.⁶

HIV infection may be associated with new-onset psychotic symptoms, typically occurring in later stages of HIV or AIDS. Persecutory, grandiose, or somatic delusions are common, with prominent auditory hallucinations and occasional affective symptoms. A prior history of methamphetamine use disorders, untreated HIV infection, and dementia are associated with psychosis and increase vulnerability.

The treatment of psychotic disorders is very similar whether the symptoms are due to an existing disorder or of new onset. Adults with AIDS are reported to have twice the risk of developing extrapyramidal symptoms (EPS) or tardive dyskinesia with conventional antipsychotics compared to patients who do not have AIDS because of the loss of dopaminergic neurons from HIV-related injury to the basal ganglia. Loss of dopaminergic neurons and decreased dopamine levels normally occur with aging, so that older HIV-positive adults are at particularly high risk for developing EPS and tardive dyskinesia. Atypical antipsychotics are therefore the treatment of choice for psychosis. Clozapine, which can cause bone marrow suppression, is highly anti- cholinergic and causes orthostatic hypotension; it should be used very cautiously in this population. Response to antipsychotics typically occurs in doses one fourth to one half of those required for treating comparable HIV-negative and younger populations.

Drug–drug interactions should also be considered. Ritonavir and lopinavir/ritonavir may increase serum levels of clozapine and risperidone and decrease serum levels of olanzapine. Doses of these antipsychotics would need to be adjusted accordingly. Fluconazole can prolong the QT interval, and there should be concern in coadministration with risperidone, quetiapine, and especially ziprasidone, which can all prolong QT intervals, particularly in older adults with comorbid cardiac disease.

Increasing age, HIV seropositivity, and schizophrenia are all independent risk factors for the development of metabolic syndrome and diabetes mellitus, so that older HIV-positive persons with schizophrenia are at particularly high risk. The use of HAART further increases this risk, as do some atypical antipsychotics. Metabolic disruptions occur more commonly with clozapine and olanzapine than with other available agents. HIV-positive older adults with psychotic disorders should be screened for risk factors for metabolic syndrome (Table 26.1), and the American Diabetes Association Consensus Guidelines⁹ for ongoing monitoring of diabetes risk should be followed (Table 26.2).