Case: A 55-Year-Old HIV-Infected Woman With Cognitive Difficulties

A 55-year-old woman with well-controlled HIV infection is brought to the clinic by her family members because she has been having trouble with repeat and recall. Her family has observed that she was forgetting such things as where she put her keys, was leaving the stove on, and was having difficulty managing her medications, preparing meals, and paying bills. She had lost a small amount of weight.

She was initially diagnosed with AIDS in 1997, with a CD4+ cell count of 18/µL. Her risk factor was unprotected sex with her husband, who did not know his status at the time. Her nadir CD4+ cell count was 0/µL in 2000 when she finally began treatment, but she quickly achieved virologic suppression. Her other medical history includes squamous cell anal cancer in the same year as her diagnosis treated with resection and radiation, and mild hypertension. The patient had no personal or inherited dementia history. She was married, with 2 grown children, and had worked in retail for nearly 10 years but stopped working around 2000 when she developed symptomatic HIV infection. She never smoked, uses no drugs, and does not drink alcohol.

She had been functioning well and living independently, with well-controlled HIV infection and normal CD4+ cell counts on tenofovir, emtricitabine, and efavirenz, until approximately 2008 when she began struggling with acyclovir-resistant recurrent vaginal herpes simplex virus (HSV) infection. She was prescribed topical cidofovir but her children and family noticed that she seemed to need repeated reminders on how to use the medication. Family members had not noted any other memory problems at that time. Later in 2008, she moved away briefly to warmer climates to live with other family members. While there, she stopped taking antiretroviral drugs to pursue herbal remedies. She felt well until approximately 3 months prior to the visit, when family members noticed the trouble with repeat and recall and brought her back for follow-up.

On presentation, she is a pleasant woman with a normal physical examination except for cognitive issues, 10-lb weight loss, and recurrence of genital herpes. She scores 19 of 30 points on an initial Mini-Mental State Examination.[12] Her CD4+ cell count is 777/µL and her plasma HIV RNA level is 442 copies/mL. Her folic acid level, rapid plasma reagin test result, vitamin B₁₂ level, thyroid-stimulating hormone (TSH) level, complete blood cell count, hepatic panel, and basic metabolic profile are within normal limits. She undergoes a lumbar puncture. The cerebrospinal fluid (CSF) has 1 white blood cell, 0 red blood cells, normal protein and glucose, and results for toxoplasmosis, cryptococcal antigen, Venereal Disease Research Laboratory (VDRL), JC virus, HSV, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus tests are negative. Given the functional decline in instrumental activities of daily living (IADL), she is also referred to a neurologist and undergoes a battery of neurologic and neuropsychologic tests, an electroencephalogram, and brain magnetic resonance imaging (MRI). The brain MRI reveals subtle ischemic change. Her electroencephalogram is unremarkable.

Clinical Decision Point A

Which is correct regarding dementia in this patient?

Despite the lack of MRI findings suggestive of HAND and the inability to obtain CSF viral load testing, the patient is clinically diagnosed with severe HAD. She is immediately restarted on antiretroviral therapy but with a new regimen of zidovudine plus lamivudine and ritonavir-boosted lopinavir to maximize CNS penetration. However, symptomatic aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level elevations to over 600 U/L develop after 2 weeks of therapy. After transaminitis resolution, she is switched to tenofovir disoproxil fumarate, emtricitabine, and raltegravir without further complications. Plasma HIV RNA quickly becomes undetectable again, but the patient has no clinical improvement.

She is examined in the neurology department 3 months after having restarted antiretroviral drugs, and because of a lack of improvement she is initiated on a 3-month trial of donepezil and memantine for possible Alzheimer’s disease. However, these medications do not change her course, either. A safety plan with more family involvement and the services of a home attendant are put in place, and over the next 2 years, her dementia remains stable.

However, after that long period of stability, her family members call to report that she has lost more skills. She is refusing to bathe unless a specific home attendant is present to help her. She has recently begun eating uncontrollably, and they have begun locking kitchen cabinets. She has also stopped recognizing most of her family members. She sometimes refuses to take her blood pressure medication and HIV regimen. On occasion, she has soiled her underwear with stool. She is scheduled for a visit the next day.

She comes to the clinic with her brother and children. She is superficially polite and groomed but is dressed more casually than on previous visits. She does not recognize any staff members. She does not want to talk to or make eye contact with the practitioner but seems comfortable standing next to her brother. She appears her stated age and is now overweight. She has not developed any other interval comorbidities. Her medications include her antiretroviral regimen, amlodipine, and a multivitamin (5 pills altogether). She still has an apartment in her own name, but a home attendant or family member is with her 24 hours a day. Some family members describe symptoms consistent with caregiver fatigue. Several staff and family members are needed to coach her into a simple blood draw to assess her HIV parameters. Laboratory test results reveal that she has a suppressed plasma HIV viral load.

Clinical Decision Point B

What is the best next step in assisting this patient and her family?

The family reports that the patient’s language skills have further deteriorated; sometimes she can and at other times she cannot carry on a phone conversation. She can still verbally express basic preferences and needs to her family and caregivers. She recognizes her brother but often does not know her children by name, although she is comfortable in their presence. She becomes agitated when a substitute aide is assigned and has been known to attempt to scratch or hit an aide she does not recognize.

The practitioner suggests a lumbar puncture in order to detect HIV RNA level in the CSF and evaluate the possibility of CSF viral escape, but the patient is less cooperative than she was a few years ago and now requires full sedation to undergo the procedure. The basic CSF results are similar to previous CSF results. However, the result of the CSF HIV RNA level test was not sent correctly from the laboratory, so discordance between sets of results could not be evaluated. The family declines a third lumbar puncture to collect this information.

The practitioner inquires more about the patient’s function. She is able to feed herself and ambulate on her own but otherwise has become dependent in all other IADL and ADL. She can go to the toilet but forgets to flush and puts the used toilet paper in inappropriate places. On at least 1 occasion, she moved her bowels during a shower.

Clinical Decision Point C

At this time the practitioner decides to seek help in caring for the patient. What is the best next step?

An article in the Journal of the American Medical Association (JAMA)[11] describes the last phase of HIV care as advanced care, with the focus on goals of care and end-of-life planning. Despite the presence of numerous and often advanced chronic illnesses and functional deficits, many people with HIV infection have never completed advance directives; in a study by Erlandson and colleagues, less than 50% had completed an advance directive, and women and those with lower educational status had even lower completion rates.[52] This patient is in the advanced-care stage. A geriatrician and a social worker join the HIV care team and begin to guide discussion about caregiver stress, dementia resources, behavioral management, medication use, and goals of care, including intubation, resuscitation, and tube feeding. Family members indicate that they can continue to care for the patient and are not interested in her institutionalization, but they describe the circumstances that would necessitate nursing-home placement, such as complete loss of bowel and bladder control. The HIV care practitioner discusses goals of care and then turns to medication management.

Despite continued challenges, the family wants to keep the patient at home and continue treatment, but she is beginning to refuse her medications, occasionally spitting out pills. They do not want to force her or restrain her for therapy but ask the HIV care practitioner what the best option is.

Clinical Decision Point D

What is the best strategy for antiretroviral therapy management if this patient cannot or will not take pills?