HIV, AIDS and Physical Therapy

- acquired immunodeficiency syndrome (secondary immunodeficiency)

- profound immunosuppression
- opportunic infections
- secondary neoplasms
neurologic manifestations

infection with the human immunodeficiency virus (HIV)- retrovirus

- in the form of RNA
- will reproduce itself in DNA (in reverse order than normal)
- reverse transcriptase

looks at elevated levels of p24 (protein) to screen for HIV
- currently questioning its accuracy

- T Helper Cells (CD4)- cd4 loss=dysfunction
- Neurological Cells
- macrophages
- dendritic cells
- NK & CD8 cells

1. HIV binding to cells and fusion
2. Injection of Viral core
3. Uncoating
4. Reverse Transcriptase
5. DNA integration
6. Viral Protein Expression (Transcription and Translation)
7. Protein Modification (mediated by protease)
8. viral Core Assembly
9. Budding

1. Early Acute Phase
2. Middle chronic Phase
3. Final Crisis Phase

- 85% of infected people experience some symptoms
- "seroconversion illness" (may experience flulike sx.)
- 3-6 weeks after infection, CD4 cell count decreased
- CD4 levels return to normal

- stage of apparent containment of the virus
- immune system is intact but viral replication continues for several years
- pts are generally asymptomatic or develop mild opportunistic infections

- eventually the replacement mechanisms can no longer keep pace and an observable decline in CD4 occurs

- pt HIV+, plus...
- CD4 count <200/uL or opportunistic infections/neoplasm, unless...
--high dose corticoid therapy or other immunosuppressive within 3 months prior to onset
--dx with WBC-related disease: lymphoma, lymphocytic leukemia, cancer of lymphoreticular or histiocytic tissue, etc.
--genetic immunodeficiency atypical of HIV
***with tx., AIDS classification can move back to HIV + only***

1. protozoa infection
2. fungi infection
3. bacterial infection
---pneumocystis pneumonia
---tuberculosis
---meningitis
4. viral infection
---herpes simplex
---CMV
5. Neoplasms
---kaposi sarcoma
---non-hodgkin lymphoma
---primary brain lymphoma
---invasive cancer of uterus

1. both are indicators of disease severity
2. CD4 count determines pts status (degree of immunosuppression) at time measure was taken
3. viral load (log RNA copies/ml) indicates the direction the infection is taking
--change>0.5 log copies/mL (~3 fold) exceeds assay and diurnal variations, --represents true biological event, whereas change<0.5 log copies/mL indistinguishable from random variability (rate of change more important than absolute no.)

1. Hepatitis C co-infection (recreational injection drugs--longer life of virus, immunocompromised from HIV)
2. Neuropathy
3. Cardiovascular Disease
4. PVD

1. Highly-active Anti-retroviral Therapy (HAART)--"drug cocktail"
2. Aimed at limiting viral replication
3. Three classes
--Reverse Transcriptase Inhibitors (NRTI and NNRTI)--competitive inhibitors
--protease inhibitors
--fusion inhibitors

1. improves immune fxn
2. suppresses viral replication
3. significant increases in life expectancy (reduction in opportunistic infections and comorbidities)
4. substantial reductions in wasting syndrome
5. prolongs chronic phase

1. pt oriented decisions on when to start and stop rx.
2. issues of drug tolerance
side effects
co-morbid conditions or incidents may necessitate halting HAART for a time
3. weighed against pt status and likelihood of imminent progression

1. >500/uL--generally asymptomatic
2. 200-500/uL--early symptoms
3. <200/uL--severe immunosuppression (one of the criteria for AIDS categorization)

1. Mitochondrial Dysfunction
--NRTIs are thought to be the main culprits
--are effective due to high affinity for the viral reverse transcriptase (a DNA polymerase)
----inhibiting HIV replication
----however, NRTIs can also bind to other DNA-polymerases
-Inhibit DNA polymerase gamma in Mitochondria
- disrupts mitDNA transcription
2. Dyslipidemia
- particularly associated with Pis
- increased triglycerides
- decreased TC, HDL, and LDL
3. Insulin Resistance
4. Greater Risk for Type II DM

fat loss in the face/limbs and fat accumulation in the belly/trunk, dorsal cervical area
--associated with drugs and not the disease

1. Impaired Aerobic Capacity (assoc with HAART, not just HIV; NRTI's assoc with reduced/mutated mitochondrial DNA)
2. limitations in physical function (decreased capacity for vigorous activity--impairments worse with symptomatology)
3. Potential associated problems (Cardiovascular Disease, PVD)

1. impaired ox capacity shown with untreated HIV and with HAART
2. with HAART, mechanism appears to be impaired O2 extraction-utilization (a-v O2 diff)
--based on VO2, people can be borderline disabled because of fitness

1. can see a "fitness disability" (Functional Aerobic Impairment (FAI))
2. fatigue is one of the primary complaints of HIV+ individuals
3. reductions in vigorous activity and high-level ADLs even in asymptomatic HIV+
--30% in asymptomatic HIV persons
--60% symptomatic
--80% in AIDS

1. common problem (38-60%)- multiple types of neuropathies are described
--virus itself, HIV drugs, or as a result of opportunistic infections or other complications
--most are sensory, and can be asymptomatic
--many are painful
2. direct mechanism of neuronal injury may be related to the HIV gp120, which can activate neural receptors for inflammatory cytokines (assoc with binding to CD4 receptor)

3. distal symmetric polyneuropathy (DSP) is most common
4. autonomic (increase risk for adverse cardiovascular events--increased vessel stiffness)
5. motor neuropathies also reported
--both at peripheral and spinal levels
--contribute to weakness
--symptoms can mimic ALS

1. with wasting, profound loss of muscle mass impair force production
2. in age of HAART, wasting is less common
3. other factors contributing to weakness (central activation deficits--with no change in CSA; associated with viral load and past Hx of AIDS defining illness; problems as a result of the disease, not the drugs)

1. relationship between CSA and strength without deficit--relationship weakened with central activation deficits

use 6 minute walk (measuring distance)
--with wasting 6MWD related to LE strength
--with HAART, relationship less strong
--6MWD an effective predictor of VO2

from age-associated comorbid conditions than AIDS

1. Functional Aerobic Status (6MWD)
2. Ankle Brachial Index (2 bp measurements)
3. Neurological Screening--protective sensation

1. Pain control--use TENS unit
2. Pt. education (manage insate feet--custom shoe fitting, etc., ADL/task modification, D/C planning)
3. Exercise

1. Vigorous exercise (>60 VO2 max, 3x/week) associated with slowed progression pre-HAART
--physical activity inversely related to viral load
--appears safe for HIV+ on or off HAART (no decrease in CD4 or increase in viral load or OI's)
--can reduce functional aerobic impairment
may improve arterial compliance (improved elasticity in animals, not humans yet)
--increase LBM and strength
--effects more pronounced in pts with wasting (gains still present without wasting)
--not all protocols are successful (nutritional status, central activation, testosterone levels)

- they are in conflict with each other
- only really concerned with this in athletes trying to reach the apex of either performance
- optimal exercise interventions have hot yet been determined

- reduces trunk fat mass and triglycerides; FAI
- increase strength and aerobic capacity