Epidemiology

1. Recent estimates show that one in six persons infected with HIV are now older than 50 years of age. This is due to longer survival of HIV-positive patients on antiretroviral therapy and increased diagnoses with wider HIV testing recommendations. The older population does not see itself as high risk, and there is little HIV prevention geared toward people older than 50. Perception among providers is that older adults are not a high-risk population and are not screened for HIV as often as younger adults. In 2009, the American College of Physicians (ACP) suggested that the age range of routine HIV screening be extended to 75 years.
2. The widespread use of antiretroviral therapy has altered the course of HIV disease. In 2012, HIV was reclassified as a chronic illness. More than 50% of deaths in HIV-positive persons on highly active antiretroviral therapy (HAART) are related to conditions other than AIDS.

Risk Factors

1. Men who have sex with men (homosexual or bisexual).
2. Heterosexual contact with an infected partner, including commercial sex workers.
3. Needle sharing by intravenous drug users (IVDU).
4. Perinatal infection: Mother-to-child transmission.
5. Open wound and mucous membrane exposure to body fluids of infected person.
6. Recipients of transfusion of contaminated blood or blood products (rare since 1985).

Pathogenesis

1. HIV belongs to a subgroup of retroviruses called lentiviruses or “slow” viruses. The course of infection of the virus is characterized by a long interval between infection and the onset of serious symptoms. CD4 cells are the primary target of HIV.
2. Primary HIV infection is followed by a burst of viremia during which the virus is easily detected in peripheral blood per HIV PCR viral load. During the “window period,” the first 2 to 6 weeks following infection, persons may test negative for the HIV antibody with the enzyme-linked immunosorbent assay (ELISA) and western blot tests. During this time, the person can be highly infectious to sexual partners. In this time of early infection with high viral load, the CD4 cells can decrease by 20% to 40%. Within 2 to 4 weeks after exposure to the virus, up to 70% of infected patients experience a flulike illness related to acute infection. The immune system fights back to reduce the HIV levels with killer T cells (CD8) that attack and kill the infected cells. The patient’s CD4 cell count may rebound by 80% to 90%. A patient can remain symptom-free for a long time, often years. During this time there is low-level replication of HIV but ongoing deterioration of the immune system. Enough of the immune system remains intact to prevent most infections. The patient is infectious during this time.
3. The final phase of HIV occurs when a sufficient number of CD4 cells are destroyed and when production of new CD4 cells cannot match destruction. Patients exhibit fatigue, fever, and weight loss. This failure of the immune system leads to AIDS.
4. An HIV-infected person can live an average of 8 to 10 years before developing clinical symptoms. HIV disease is not uniformly expressed in all people. A small portion of patients develop AIDS and die within months of infection. Approximately 5% of infected patients, known as “long-term nonprogressors,” have no signs of disease after 12 or more years.
5. Most AIDS-defining conditions are marked by a CD4 count of less than 200 cells or the appearance of one or more of the opportunistic infections (OI). Bacteria, viruses, or fungi that would not cause illness in a healthy immune system cause OI. These infections are often severe and sometimes fatal.
6. Research shows age-related immune system dysfunction associated with decreased CD4 cell response to antiretroviral therapy due to thymus involution.
7. Untreated HIV in patients older than age 50 show a more rapid progression toward AIDS and poor overall survival.

Common Complaints

1. Fatigue: Often severe.
2. Fever: Longer than 1 month.
3. Night sweats: Drenching.
4. Loss of appetite.
5. Weight loss.
6. Rash.

Other Signs and Symptoms

1. Lymphadenopathy: Enlarged lymph nodes often involving at least two noncontiguous sites.
2. Anemia.
3. Neutropenia.
4. Thrombocytopenia.
5. Cough.
6. Dyspnea.
7. Asymptomatic whitish patches on sides of tongue: Hairy leukoplakia.
8. Thrush: Oral candidiasis.
9. Odynophagia: Esophageal candidiasis, cytomegalovirus (CMV), esophagitis.
10. Chronic vaginal candidiasis.
11. Skin changes: Rashes, dry skin, and seborrheic dermatitis.
12. Purplish, nonblanching nodules found on the skin, mucous membranes, and viscera: Kaposi’s sarcoma.
13. Muscle wasting.
14. Chronic diarrhea: Longer than 1 month.
15. Hepatosplenomegaly.
16. Cardiomyopathy.
17. Chronic bacterial infections, including community-acquired pneumonias.
18. Tuberculosis (TB).
19. Sexually transmitted infections (STIs).
20. Peripheral neuropathy.
21. Dementia.

Subjective Data

1. Review symptoms: Onset, course, and duration.
2. Ask about previous HIV testing: Dates and reasons for testing.
3. Past medical history review: Hospitalizations, comorbidities, immunizations, normal weight, pain, chronic lymph node disorders, and any changes of skin overlying lymph nodes.
4. Past surgical history review.
5. Sexual history: Number of partners in the past year, number of lifetime partners, any previous partner known to be HIV positive or have STIs, and any previous partners known to have been incarcerated:
   1. Women: History of abnormal Pap smears, contraception, and condom use with partner.
   2. Men: Men having sex with men (MSM), heterosexual, bisexual, receptive anal intercourse, and condom use.
6. Past mental health history: Past and current mental health diagnosis and treatment.
7. Substance use: Tobacco, alcohol, and drugs.
8. History of IVDU: Needle sharing and when last used drugs.
9. Transfusion or blood product history prior to 1985.
10. Lived or traveled outside of the United States: When and for how long?
11. Assess the presence of persistent fever with no localizing symptoms.
12. Assess the patient’s support system: Who knows about their diagnosis?

Physical Examination

1. Height, weight, blood pressure, pulse, respiratory rate, and temperature. Calculate the patient’s body mass index (BMI) at each office encounter.
2. General observation: General appearance, including fat distribution, signs of wasting.
3. Inspect:
   1. Skin: Evaluate for rashes, seborrhea, folliculitis, moles, Kaposi’s sarcoma, warts, herpes, dry skin, skin cancer, fungal infections, molluscum contagiosum, jaundice, and needle marks.
   2. Head and neck; eyes, ears, nose, and throat (HEENT):
      1. Assess visual acuity.
      2. Retina exam for CMV.
      3. Evaluate sclera for icterus.
      4. Oral exam for thrush, hairy leukoplakia, mucosal Kaposi’s sarcoma, gingivitis, aphthous ulcers, and dental health.
4. Auscultate:
   1. Pulmonary auscultation for air movement and abnormal breath sounds.
   2. Cardiac evaluation for normal and abnormal heart sounds.
5. Palpate:
   1. Palpate the thyroid.
   2. Lymphatic evaluation of regional versus generalized swelling: Specific location, size, and texture of nodes.
   3. Palpate the abdomen to evaluate the presence of hepatosplenomegaly, masses, tenderness, pain, or rebound tenderness.
6. Rectal/vaginal examination:
   1. Both genders: Inspect for the presence of ulcers and warts in the vagina, on the penis/testes perineum, and in the rectum.
   2. Females: Perform bimanual examination and Pap smear with HPV testing, obtain specimens for STI testing, and perform a digital rectal exam and anal Pap smear, if indicated.
   3. Males: Perform testicular exam, digital rectal exam; consider an anal Pap if indicated.
7. Neurologic examination:
   1. Assess mental status.
   2. Assess cranial nerves, including gait, strength, deep tendon reflexes (DTRs); evaluate proprioception, vibration, pinprick, temperature, and sensation in distal extremities.
8. Psychiatric examination: Screen for depression.

Diagnostic Tests

1. Repeat HIV ELISA and western blot.
2. Complete blood count (CBC) with differential, including platelets.
3. Complete chemistry profile.
4. Fasting lipid profile.
5. Venereal disease research laboratory and rapid plasma reagin.
6. Serologies for toxoplasmosis.
7. CD4/CD8 cells and CD4/CD8 ratio.
8. HIVRNA viral load.
9. HIV resistance genotype.
10. HLA-B 5701 (risk for Abacavir hypersensitivity reaction syndrome).
11. Hepatitis serologies: Hepatitis A virus (HAV) serology (antibody); hepatitis B virus (HBV) serology (HBsAb, HBeAb, HBsAb); and hepatitis C virus (HCV) serology (antibody).
12. Cultures for STIs: Anal, vaginal (culture pharynx if history indicates oral sex).
13. Urinalysis.
    1. Pap smear with human papillomavirus (HPV) testing.
14. TB screening.

Differential Diagnoses

1. HIV.
2. Other diseases that lead to immune suppression or are related to symptoms.
3. Cancer.
4. Chronic infections.
5. TORCH infections.
6. Syphilis.
7. TB.
8. Endocarditis.
9. Infectious enterocolitis.
10. Bowel disorders: Antibiotic-associated colitis, inflammatory bowel disease, or malabsorptive symptoms.
11. Endocrine diseases.
12. Neuropathy.
13. Alcoholism.
14. Liver disease.
15. Renal disease.
16. Thyroid disease.
17. Vitamin deficiency.
18. Chronic meningitis.

Plan

1. General interventions:
   1. Refer and comanage the patient with HIV/AIDS clinician.
   2. Identify and refer for treatment of substance abuse.
   3. Explain to the patient that each visit will include a review of history, a physical exam, and laboratory studies to assess health status.
   4. Discuss health habits: Smoking, nutrition, and exercise.
   5. Discuss treatment plan:
      1. HAART.
      2. Therapy for OI and malignancies.
      3. Prophylaxis for OI: Pneumocystis pneumonia (PCP) and mycobacterium avium complex (MAC).
      4. Management of side effects of medications and comorbidities.
      5. Immunizations.
2. Patient teaching:
   1. Discuss living with HIV disease.
   2. Discuss transmission prevention strategies: Safer sex practices and condom use.
   3. Provide contact information for AIDS social service organizations (ASO).
   4. Discuss the patient’s concerns, including notification of sexual partner(s) and needle-sharing partner(s).
   5. See Section III: Patient Teaching Guide “Reference Resources for Patients With HIV/AIDS.”
3. Pharmaceutical therapy:
   1. Treatment with HAART. The Department of Health and Human Services (DHHS) guidelines on the treatment of HIV/AIDS recommended HAART for all HIV-infected patients regardless of CD4 cell count.
   2. Polypharmacy is one of the biggest challenges in caring for the aging population. The average HIV-negative patient older than 50 years old takes an average of five medications. These added to three to five or more HIV medications complicates monitoring for medication interaction and side effects. Comorbidities, existing medications, and potential organ toxicities should all be considered in choosing a HAART regimen.
   3. HAART (Public Health Service Task Force Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents) classes:
      1. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).
      2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
      3. Protease inhibitors (PIs).
      4. Integrase inhibitors (INIs).
      5. Fusion inhibitors (FIs).
      6. C-C chemokine receptor type 5 (CCR5).
      7. Combination antiretrovirals—pill formulations with multiple antiretroviral medications.
   4. Prophylaxis and treatment for OIs. May discontinue prophylaxis if sustained immune reconstitution on HAART:
      1. PCP: Prophylaxis if CD4 count is less than 200 or if the patient has oral candidiasis:
         1. First-line: Bactrim DS (trimethoprim/sulfamethoxazole [TMP-SMZ]), one tablet three times weekly or one tablet daily (if toxoplasmosis is positive).
         2. Alternatives: Dapsone, atovaquone, and aerosolized pentamidine.
      2. MAC: Prophylaxis if CD4 count is less than 75:
         1. First line: Zithromax 1,200 mg weekly.
         2. Alternative: Clarithromycin.
   5. Managing the side effects of HAART, complications of HIV therapy, and aging population: There are multiple complications of long-term HIV infection and treatment with HAART. Age-related decrease in renal and hepatic function should be considered when choosing a HAART regimen. These problems can lead to higher levels of HIV medications and increased toxicities. There are no guidelines for dose adjustment based on age but renal and hepatic function should be monitored on an ongoing basis and adjustments made accordingly. Other considerations for HAART choices include immunizations—(live virus vaccines contraindicated unless CD4 count >200—varicella; measles, mumps, rubella [MMR]):
      1. Hepatitis A and B series.
      2. Tetanus.
      3. Pneumococcal vaccine.
      4. Yearly influenza vaccines.
      5. Tdap booster as needed.
      6. Shingles vaccine contraindicated in HIV patients.
   6. Complications associated with both HIV-positive and with older populations requiring diligent monitoring:
      1. Osteoporosis—HIV/AIDS patients are at high risk for decreased bone density.
      2. Hypogonadism—common in men with AIDS.
      3. Neuropsychiatric disorders—depression, anxiety, and substance use are common in the HIV population. There is increased risk for HIV-related dementia.
      4. Peripheral neuropathy—common side effect with older HIV medications.
      5. Cardiovascular disease (CVD)—HIV-related disorders such as insulin metabolism, diabetes, lipodystrophy, dyslipidemia, and hypertension. CVD complications are among the leading causes of death in HIV disease.
      6. Malignancies—liver, anal, cervical, and lung cancers are common in HIV/AIDS patients.
      7. Menopause—early menopause has been described, and the use of hormone replacement therapy has not been adequately studied in the HIV population

Follow-Up

1. Schedule return visit 4 to 6 weeks after initial visit to discuss staging HIV/AIDS and living with HIV/AIDS.
   1. More frequent visits are needed with a new diagnosis and initiation of HAART. Once HIV is suppressed, less frequent visits are required, generally every 4 to 6 months.
2. TB screening annually.
3. Pap smear:
   1. Initially, if normal, repeat in 6 months, then yearly if it remains normal.
   2. If abnormal, follow guidelines by the American Society of Colposcopy and Cervical Pathology (ASCCP).
4. Annual Pap smears for patients as indicated.
5. Urinalysis yearly if taking a tenofovir-containing regimen.
6. STI screening initially, then yearly if high risk.
7. Other annual screening as per the U.S. Preventive Services Task Force (USPSTF) and HIV/AIDS Treatment Guidelines ( AIDSinfo.NIH.gov/guidelines). Free mobile HIV/AIDs treatment guidelines apps are available through the App Store and Google Play.

Consultation/Referral

1. Refer the patient to a specialist in HIV for management of continued care and pharmacologic therapy.
2. Refer the patient to a nutritionist for baseline evaluation and diet counseling.
3. Perform vision screening yearly.
4. Require dental care every 6 months.
5. Make hepatology referral if chronic, active hepatitis B and/or C. Truvada is approved for HBV treatment.

Individual Considerations

1. Preexposure prophylaxis (PrEP) is a prevention method for HIV-negative partners:
   1. Truvada is Food and Drug Administration (FDA) approved for use as PrEP among heterosexual and MSM HIV-negative partners. One tablet is taken daily to reduce the risk of infection. Those taking PrEP should be monitored for potential side effects.
2. Postexposure prophylaxis (PEP):
   1. PEP—depending on exposure type and severity, postexposure antiretroviral treatment (ART) should be started as quickly as possible and be taken for 4 weeks:
      1. Expert consultation should be obtained as quickly as possible (National HIV/AIDS Clinician’s Consultation Center PEPline, 1-888-448-4911).
      2. Follow with occupational health for regular clinical assessment and labs.
      3. Perform HIV testing with HIV RNA, viral load, if an illness compatible with seroconversion illness occurs (fever, lymphadenopathy, pharyngitis, and rash).
      4. Advise transmission precautions during first 3 to 6 months postexposure (use condoms, refrain from donating blood, etc.).
3. Pregnancy:
   1. Refer or work very closely with the HIV OB specialist:
      1. Prenatal HIV antiretroviral therapy.
      2. Intrapartum issues for example, rupture of membranes, mode of delivery.
      3. Antiretrovirals (PEP) for the neonate.
      4. Ruling out HIV in the infant born to a HIV+ mother.
4. Geriatrics:
   1. Seniors are at increased risk for STIs due a a weaker immune system, hormone changes, and increased vaginal friability.
   2. Medicare offers free STI screening and treatment for seniors.
   3. Clinicians need to incorporate a full sexual history when assessing senior patients:
      1. Lack of sexual education: Older adults are less likely to perceive themselves at risk. Safe sex and STI prevention education started in the 1980s; during the time today’s older adults were middle-aged and not the targets of safe sex messaging. Seniors may feel sex education is only directed to youth and those wishing to prevent pregnancy.
      2. Medications for erectile dysfunction have contributed to an increase in sexual activity throughout men’s older years.
      3. Online dating may increase the likelihood that partners are unaware of the background and sexual history of partners.
      4. Postmenopausal women, without concern for pregnancy, may not feel that condoms are required with sexual intercourse.