Management of Patients with Immunodeficiency Disorders and HIV/AIDS

By Linda Self

Immunodeficiency defined

 Decreased or compromised abiity to respond to antigenic stimuli by appropriate cellular immunity reaction.

 May be secondary to loss of immunoglobulins or an abnormality of B or T cell lymphocytes

Immunodeficiency

 Primary —inborn errors. Can affect lymphocytes, phagocytes, complement system  Secondary —More common and may be related to underlying diseases or the treatment of these diseases.

Primary immunodeficiency disorders

 More than 100 identified  Examples include: Immunoglobulin A deficiency, thymic hypoplasia, severe combined immunodeficiency disease, granulomatoses

Causes of secondary immunodeficiency

 Malnutrition  Burns  Uremia  Diabetes mellitus  Immunotoxic medications  Self-medication of recreational drugs and alcohol  AIDS

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Nursing Management for Patient with Immunodeficiencies in general

Assess for infection Fever White patches in oral cavity Adenopathy Persistent diarrhea Frequency, urgency or pain upon urination Redness, drainage or swelling of skin lesions Persistent vaginal discharge Cough with or w/o sputum

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 Monitor lab values Sputum Urine Blood cultures CBC Monitor vital signs, weight

     Assess nutritional status ?use of tobacco, alcohol or drugs Personal hygiene practices Dental hygiene Teaching patient s/s of infection

Preventing Infection in the hospitalized neutropenic patient

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Still w/o evidence-based consensus

 Private room  Low microbial foods  Protective clothing  Skin asepsis  Ice chips to prevent mucositis  Avoid rectal introduction of meds, treatments

HIV/AIDS

 Public awareness in 1981  First antiretroviral drug in 1987  PCP prevention started in 1988  1995 protease inhibitors

Epidemiology

 CDC surveillance/reportable illness  African-Americans account for 50% of cases in 200  Highest incidence in CA, NY, and FL  Kills more than 8000 cases per day worldwide  Now considered a disease of chronicity  Older adults at risk for HIV infection

 Women are fastest growing group w/HIV  Women have poorer outcomes  Fatality rate is 60%  Hits hardest between 25-44 years of age

Sexual Transmission

 Virus is most concentrated in semen and blood  Most easily transmitted when infected body fluids come into contact with mucous membranes or non-intact skin  Genital, anal or oral sexual contact with exposure of mucous membranes to infected semen or vaginal secretions

Viral Load

 Higher the blood level of HIV, the greater the risk for sexual and perinatal transmission  Effects of highly active antiretroviral therapy have been instrumental in causing the viral load to drastically drop in some individuals

HIV Transmission

 Not by casual contact  By body fluids such as breast milk, semen, vaginal secretions, amniotic fluid, and blood

Pathophysiology

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Caused by an RNA virus or retrovirus Replication goes as follows: HIV GP 120 and GP41 to CD4 cell receptor Viral core empties into cell Reverse transcriptase copies RNA into double stranded DNA Integration of viral DNA into host DNA w/aid of integrase Using integrated DNA as blueprint, makes new viral proteins Translation of viral messenger RNA to create polyprotein Protease cleaves the strand Assembly and release of new virus

Pathophysiology

 HIV attacks T cells  T Cells are lymphocytes  Have a special receptor on cell surface  Different subsets of T cells  CD4+ helper T Cells (release cytokines) instrumental in initiating the immune response both with B lymphocytes, macrophages and NK cells

Pathophysiology cont.

    Cytotoxic T cells or CD8+ cells destroy virally infected cells, tumor cells and induce transplant rejection Memory T cells-persist long-term. Can be CD4 or CD8 cells Regulatory T cells-suppressor T cells. Shut down T cell mediated immunity at end of immune reaction Natural killer cells bridge adaptive immune system with innate immune system. Target damaged, infected or dysfunctional cells.

 AIDS renders the immune function ineffective  Targets cells with the CD4 and CCR5 glycoprotein receptors which is primarily on T lymphocytes, monocytes, dendritic cell  Mutation of CCR5 occurs in some Caucasians allowing for greater posssible immunity

Stages of HIV Disease

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Clinical Category A

 Includes one or more of the following in an adult or adolescent and w/o conditions in clinical categories B and C  Asymptomatic HIV infection, persistent generalized lymphadenopathy, acute HIV infection with accompanying illness

Stages cont.

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Clinical Category B

Candidiasis, oropharyngeal or vulvovaginal (persistent and poorly responsive) Cervical dysplasia/cervical CA in situ Fever or diarrhea exceeding one month Hairy leukoplakia Herpes zoster affecting more than one dermatome ITP PID Peripheral neuropathy

Stages cont.

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Clinical Category C

Candida of esophagus, trachea +/or bronchi Invasive cervical cancer Cryptosporidiosis exceeding one month CMV disease (other than liver, spleen or lymph) HIV encephalopathy CMV retinitis Histoplasmosis Kaposi’s sarcoma MAC, MTB Toxoplasmosis of brain Wasting syndrome Pneumcystis jiroveci

CD4+ T-cell Categories A, B, C

1. greater than or equal to 500/uL 2. 200-499/uL 3. <200 u/L People with AIDS indicator conditions (clinical category C) and those in categories A3 or B3 are considered to have

AIDS

Assessment and Diagnostic Findings

      Health history IV injection drug use Receipt of blood transfusions Exposure to body fluids HIV antibody tests —EIA (enzyme immunoassay), Western blot confirms EIA OraSure saliva test and the OraQuick Rapid HIV antibody test (approx. 20 minutes and is 99.6% accurate)

Viral Load

     Measures plasma HIV RNA levels Reverse transcriptase polymerase chain reaction and nucleic acid sequence based amplification Both are target amplification methods to quantify HIV RNA or DNA levels Viral load is a better predictor of the risk for HIV disease progression than is the CD4+count Lower the load, longer the time to AIDS

Treatment

 CD4+ count is most important consideration in starting HAART  Antiretroviral medications should be offered to those w/T cell count less than 350 cells/mm3 or plasma HIV RNA levels >100,000 copies/mL  Goals: sustain suppression of viral load, preserve or restore immunologic function, improve quality of life, reduce HIV morbidity and mortality

Treatment

 Ongoing treatment response evaluation  Viral load levels before initiation of HAART and again after 2-8 weeks  CD4+ count should increase by 100 to 150 cells/mm3 per year  Viral load should continue to decline over several weeks and drop below detectable levels <50 RNA copies/mL by 16-20 weeks

HAART

 Mechanics of virus replication targeted  Medications target reverse transcriptase, integrase, protease and actual receptors to slow disease progression

Antiretroviral Agents

     Currently over twenty agents in more than four classes NRTIs —Abacavir (ABC), Videx (didanosine), Epivir (lamivudine), Zerit (stavudine) NNRTIs —Rescriptor (delavirdine), Viramune (nevirapine) Protease Inhibitors —Agenerase (amprenavir), Norvir (ritonavir), Viracept (nelfinavir) Fusion Inhibitors —Fuzeon (enfuvirtide)

Treatment

 Always combination therapy  Decrease pill burden  Compliance is an issue  All medications have adverse effects — lipodystrophy, hyperlipidemia, heart disease and diabetes, changes in body image

Drug Resistance

  Results from spontaneous genetic mutation of the pathogens or in response to exposure to the medication Contributing factors —monotherapy, suboptimal treatment regimens, nonadherence, late initiation of therapy  Virologic failure will manifest first, then immunologic failure

Drug Resistance

 To better predict the likely susceptibility of drug therapy,

genotype

testing determines amino acid mutations 

Phenotype

testing determines the drug concentration needed to inhibit replication of a recombinant virus by 50% of a patient’s isolate

Clinical manifestations

    May affect any organ Can develop

immune reconstitution syndromes w/

MAC, MTB, PCP, toxoplasmosis, hepatitis B &C, CMV, VZ, cryptococcal infection, PML (progressive multifocal leukoencephalopathy) Is a paradoxical inflammatory reaction when innate immunity improves after tx with HAART Will have high fevers and worsening infection symptoms temporarily

Respiratory Manifestations

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PCP

—most common infection with AIDs.

Pneumocystis

pneumonia Now called

Pneumocystis jiroveci

Without prevention, 80% of those with HIV will develop PCP Fever, chills, SOB, productive cough Bronchoscopy Treat with Bactrim which also confers cross protection to toxoplasmosis

Mycobacterium Avium

complex

 Common opportunistic infection  Group of acid-fast bacilli that includes

M.

avium, M. intracellulare

and

M.

scrofulaceum

 Treat with Zithromax or Biaxin, possibly Mycobutin.  Duration of tx depends on CD4+counts

Tuberculosis

     Occurs late in HIV infection Absence of immune response to TB test=

Anergy

Infection may become disseminated Multi-resistance occurring Paradoxical reaction more commonly with this infection. Seen as high fevers, worsening pulmonary infiltrates, expanding CNS lesions and worsening lymphadenopathy. Seen in those with TB and HIV who are on anti-retrovirals.

Gastrointestinal Manifestations

      Loss of appetite Nausea and vomiting Oral and esophageal candidiasis Chronic diarrhea Pathogens include:

Cryptosporidium muris

, salmonella,

Giardia

,

Clostridium difficule

and

Isospora belli.

May have to treat with sandostatin if s/s not controlled (decreases motility and secretion of water)

GI Manifestations

 Oral candidiasis  Wasting syndrome —weight loss of more than 10% and diarrhea for more than one month Anorexia, diarrhea, GI malabsorption and lack of nutrition in chronic disease are contributors  Hypermetabolic state resulting in cachexia

Oncologic Manifestations

        Results from altered immune response and possible stimulation of developing cancer cells

Kaposi’s sarcoma

—most common HIV related malignancy Is associated with Herpes virus 8 Skin signs manifest as CD4+ count declines Appear brownish pink to deep purple, flat or raised and surrounded by ecchymoses and edema Involvement can occur of internal organs Confirm by biopsy Tx-surgical excision, radiation, alpha-interferon IV

Oncologic Manifestations

B cell lymphomas

  Second most common malignancy in AIDS Seen in younger individuals, develop most commonly in brain, bone marrow, GI tract    Aggressive, high grade and usually in multiple sites Treatment less effective due to numerous other co-existent problems Tx —radiation and chemotherapy

Neurologic Manifestations

 Include central, peripheral and autonomic functions 

HIV encephalopathy

characterized by progressive decline in cognitive, behavioral and motor functions.

 Direct result of HIV infection  Initiates release of toxins or lymphokines that result in cellular dysfunction

HIV Encephalopathy cont.

 Signs and symptoms: fatigue, depression, memory deficits, headache, confusion, psychomotor slowing, apathy, and ataxia.

  Later stages reveal vacant stare,spastic paraparesis, hyperreflexia, hallucinations, tremor, incontinence, seizures, mutism and death.

Diagnosis —by CT, MRI, LP and brain biopsy

Neurologic Manifestations

Cryptococcal meningitis

 by

C. neoformans

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S/S – fever, headache, malaise, stiff neck, nausea, vomiting, mental status changes, and seizures.

  Dx —LP.

Tx —IV amphotericin B w/or w/o Diflucan. May need to give amphotericin intrathecally if not responsive IV. Oral Diflucan for lifelong suppressive therapy.

Neurologic Manifestations cont.

Progressive multifocal leukoencephalopathy

— a demyelinating CNS disorder that affects the oligodendoglia. Caused by

JC virus

, a papoma virus.

  S/S —blindness, aphasia, muscle weakness, paresis and death. Tx —antiretroviral therapy, research being done on interferon

Gynecologic manifestations

 Ulcerative STDs —chancroid, syphilis, herpes  Genital warts  Cervical intraepithelial neoplasia  PID  Menstrual irregularities

Integumentary Manifestations

 KS  Herpes zoster  Herpes simplex  Molluscum contagiosum  Generalized folliculitis  Skin rash from Bactrim

Endocrine Manifestations

 Any endocrine organ can be affected  S/S will present according to organ involved

Cytomegalovirus Retinitis

      Leading cause of blindness in patients with AIDS Prophylaxis with oral ganciclovir may be indicated in those with CD4+ counts less than 50 cells/mm3 Also can use Foscavir (foscarnet) Must be taken for life Adverse effect to ganciclovir is neutropenia Must be cautious with co-administration of these meds with antiretroviral drugs

CMV Retinitis

Nutrition Therapy

 High protein, high calorie diet  Enteral feedings  Appetite stimulants such as Megace (inhibits cytokine IL-1),Marinol  Advera-special nutritional supplement developed for those with HIV

Antidepressant therapy

 Ritalin as a psychostimulant (but consider effect on appetite and sleep)  ECT when severe  Prozac, Tofranil and Norpramin per text (consider drug interactions)

Nursing Diagnoses

      Diarrhea related to enteric pathogens or HIV infection Risk for infection related to immunodeficiency Ineffective airway clearance related to PCP, increased secretions, decreased ability to cough Imbalanced nutrition, less than body requirements PC: opportunistic infections; impaired breathing; wasting syndrome; fluid and electrolyte imbalances; adverse reactions to medications Social isolation related to stigma of disease, fear of infecting others

Nursing Assessments

        Identification of risky sexual practices, drug use (IV) Physical assessment Respiratory status Nutritional status Skin integrity Neurologic status Fluid and electrolyte balance Knowledge level

Nursing Interventions

 Improving airway clearance  Preventing infections  Maintaining thought processes  Improving activity tolerance  Promoting skin integrity  Promoting usual bowel patterns  Relieving pain and discomfort  Improving nutritional status

Nursing Interventions

 Decreasing sense of isolation  Coping with grief  Monitoring and managing potential complications-respiratory failure, cachexia, side effects of medications  Teach self-care

Evaluation

         Maintains effective airway Maintains usual level of thought processes Resumes usual bowel habits Maintains skin integrity Experiences no infections Maintains adequate level of activity tolerance Maintains adequate nutritional status Progresses through grief process Remains free of complications

Case Study

 JO is a 42 year old male who resides with his partner. JO was diagnosed several months ago when he presented to the doctor’s office with dysphagia, chronic cough, diarrhea, weight loss, night sweats, lymphadenopathy and fever, all lasting well over a month.

 What pathogen or pathogens might account for his cough?

 What medication(s) might we use to treat him?

 Why does he have diarrhea? What causative pathogens could be causing this?

 Why do patients with AIDS lose weight? What medications might we give to increase appetite?

 Why might JO have a sore throat?

 JO subsequently developed visual blurring. What pathogen might be causative? How would we treat this?

 What lab tests may have been used to arrive at his diagnosis of AIDS? What category would he be, given his conditions?

 What treatments might we institute to slow the progression of his illness?

 JO was started on didanosine, nevira and norvir. Thereafter, JO’s symptoms markedly improve. His CD4 count improved from 200 to 500. However, after being on this combination therapy for several months, JO developed lipoatrophy of his face and legs and his triglycerides were 6000. Which drug warrants discontinuation?

 JO is now on Trizir and is doing satisfactorily.